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Receptors

Receptors are proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis located either on the surface of or within a cell that can bind BIND Hyperbilirubinemia of the Newborn to signaling molecules Signaling molecules Second Messengers known as ligands (e.g., hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types) and cause some type of response within the cell. Surface receptors are bound to the cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane, receive signals from their surrounding environment, and transmit those signals into the cell, often via the generation of 2nd messengers (like cyclic adenosine monophosphate Adenosine monophosphate Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position. Purine and Pyrimidine Metabolism ( cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors)) or through phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing cascades. There are multiple different subclasses of surface receptors, and 3 of the most important classes include ligand-gated ion channel receptors, enzyme-linked receptors (the most common of which are receptor tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinases Kinases Macrolides and Ketolides (RTKs)), and G-protein-coupled receptors (GPCRs). Intracellular receptors, on the other hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy, are located within the cytoplasm and often act as transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription factors, directly interacting with DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure and affecting gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics expression.

Last updated: Sep 8, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Receptors are proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis located either on the surface of or within a cell that can bind BIND Hyperbilirubinemia of the Newborn to signaling molecules Signaling molecules Second Messengers known as ligands (e.g., hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types) and cause some type of response within the cell. 

General physiology

  • Ligand binds to receptor → induces a conformational change in the receptor protein
  • Ligand may come from:
    • Direct contact, through gap junctions Gap Junctions Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. The Cell: Cell Junctions
    • Endocrine and paracrine signaling (via hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types)
    • Synaptic signaling (via neurotransmitters)
  • The signaling transduction Transduction The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a gene transfer technique. Bacteriology pathway within the cell is usually a complex, multistep process.
  • End results may include:
    • Altering gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics expression (↑ or ↓ production of specific proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis)
    • Opening and/or closing membrane channels Channels The Cell: Cell Membrane
    • Release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of cellular products into the extracellular fluid Extracellular fluid The fluid of the body that is outside of cells. It is the external environment for the cells. Body Fluid Compartments (ECF) or bloodstream
    • Muscle contraction

Classification: Cell Surface vs. Intracellular Receptors

Receptors can be broken down into 2 main categories: cell surface (transmembrane) receptors and intracellular receptors.

Cell surface receptors (transmembrane receptors)

  • Located within the plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products membrane (PM)
  • Consists of 3 domains:
    • Extracellular ligand-binding domain
    • Hydrophobic domain within the PM
    • Intracellular domain
  • Ligands which use transmembrane receptors are usually unable to pass through the membrane itself because they are hydrophilic Hydrophilic Aminoglycosides and/or large.
  • The intracellular domain communicates the signal within the cell via:
    • Covalent modification of other molecules:
      • Usually via phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing, triggering a phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing cascade
      • Phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing cascade: a multistep sequence in which a phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes group is passed from 1 molecule to the next by a series of enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes known as kinases Kinases Macrolides and Ketolides
    • Generation of 2nd messengers, the most common of which include:
      • Cyclic AMP ( cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors)
      • Cyclic GMP ( cGMP cGMP Guanosine cyclic 3. Phosphodiesterase Inhibitors)
      • Inositol trisphosphate Inositol trisphosphate Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4, 5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1, 4, 5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell’s endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. Second Messengers (IP3)
      • Diacylglycerol Diacylglycerol Second Messengers ( DAG DAG Second Messengers)
      • Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)2+ ions
  • Subtypes of cell surface receptors:
    • Ligand-gated (chemically gated) ion channel receptors
    • G-protein-coupled receptors (GPCRs)
    • Enzyme-linked receptors (most common type: receptor tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinases Kinases Macrolides and Ketolides (RTKs))
Three primary types of cell surface

Three primary types of cell surface (i.e., transmembrane) receptors:
chemically gated ion channels Channels The Cell: Cell Membrane, enzymatic receptors, and G-protein-coupled receptors (GPCRs)

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Intracellular receptors

  • Located within the cell; may be in either:
    • Cytoplasm
    • Nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles
  • Consists of 3 domains:
    • Ligand-binding domain
    • DNA-binding domain
    • Domain that can interact with other transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription factors (e.g., coactivators, repressors)
  • Ligands are usually small hydrophobic molecules that can cross the cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane.
  • Examples of intracellular receptors:
    • Steroid hormone nuclear receptors
    • Vitamin D Vitamin D A vitamin that includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Fat-soluble Vitamins and their Deficiencies receptor
    • Guanylate cyclase Guanylate cyclase An enzyme that catalyzes the conversion of GTP to 3. Diarrheagenic E. coli (the NO receptor that functions as an enzyme, generating cGMP cGMP Guanosine cyclic 3. Phosphodiesterase Inhibitors)
Intracellular receptors

Intracellular receptors:
Intracellular receptors may be located within the cytoplasm or the nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles. Receptors located within the cytoplasm move into the nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles once they bind BIND Hyperbilirubinemia of the Newborn with their ligand (i.e., hormone). Within the nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles, the hormone-receptor complex binds to hormone response elements (HREs), which are specific sequences of DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure. The complex then binds other transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription factors to alter gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics expression.

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Table: Receptor types and ligands
Receptor types Example of ligands
Intracellular receptors Nuclear receptors Steroid hormones Steroid hormones Steroid hormones produced by the gonads. They stimulate reproductive organs, germ cell maturation, and the secondary sex characteristics in the males and the females. The major sex steroid hormones include estradiol; progesterone; and testosterone. Hormones: Overview and Types (e.g., glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids)
Cell surface receptors GPCRs Catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones
RTKs Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin
Ligand-gated ion channels Channels The Cell: Cell Membrane Acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS ( ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS)

Ligand-gated Ion Channel Receptors

Ligand-gated (chemically gated) ion channel receptors are a subtype of cell surface receptors.

Structure

  • Consist of multiple transmembrane subunits around a central ion-conducting channel
  • Have an extracellular (or intracellular) ligand-binding site 
Ligand-gated (chemically-gated) ion channels

Ligand-gated (chemically gated) ion channels Channels The Cell: Cell Membrane:
This image demonstrates a ligand (tan ball) binding with a ligand-gated ion channel receptor (green structure), which causes a conformational change in the channel, allowing ions to pass through.

Image by Lecturio.

Physiology

  • Ligand (e.g., ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS) binds to the ion channel receptor.
  • Induces a conformational change → channel opens 
  • Ions flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure down their electrochemical gradient Electrochemical gradient The Cell: Cell Membrane through the channels Channels The Cell: Cell Membrane (e.g., Na+, K+, Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)2+, and/or Cl).
  • This can result in:
    • Transmission of nerve signals
    • Muscle contraction
    • Release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types
    • T cell activation T cell activation Adaptive Cell-mediated Immunity
  • When the ligand dissociates → channel closes

Example of clinical relevance

Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis (MG): an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles Skeletal muscles A subtype of striated muscle, attached by tendons to the skeleton. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles. Muscle Tissue: Histology caused by dysfunction/destruction of acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS receptors (AChRs) at the neuromuscular junction Neuromuscular junction The synapse between a neuron and a muscle. Skeletal Muscle Contraction (NMJ) (a type of ligand-gated ion channel receptor). When ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS binds, the channels Channels The Cell: Cell Membrane open, allowing an influx of Na+ into the cell, resulting in depolarization Depolarization Membrane Potential that ultimately leads to muscle contraction. Without normal AChRs, muscle contraction is abnormal, and MG presents with fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, ptosis Ptosis Cranial Nerve Palsies, dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. 

Enzyme-linked Receptors

Overview

  • Receptors that have some type of enzymatic activity when “activated” by their ligand
  • Frequently kinases Kinases Macrolides and Ketolides: enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes that catalyze the transfer of a phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes group from 1 molecule to another
    • RTKs:
      • Most common type
      • Over 90 RTK genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure identified
    • Serine-threonine kinases Kinases Macrolides and Ketolides (STKs)
  • Kinase-associated receptors: Receptors do not possess intrinsic kinase activity themselves but bind BIND Hyperbilirubinemia of the Newborn kinases Kinases Macrolides and Ketolides when activated.
  • RTKs are involved in a number of processes frequently associated with general cellular function:
    • Cell cycle Cell cycle The phases of the cell cycle include interphase (G1, S, and G2) and mitosis (prophase, metaphase, anaphase, and telophase). The cell’s progression through these phases is punctuated by checkpoints regulated by cyclins, cyclin-dependent kinases, tumor suppressors, and their antagonists. Cell Cycle
    • Cell growth and proliferation
    • Cell migration
    • Cell metabolism

Structure of RTK

  • Extracellular domain containing the ligand-binding site 
  • Intracellular kinase domain
  • Single transmembrane helix linking extracellular and intracellular components
The three part structure of the rtks

The 3-part structure of the receptor tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinases Kinases Macrolides and Ketolides (RTKs) is shown along with ligands binding to their extracellular binding sites.

Image by Lecturio.

Signaling pathway of RTKs

  • Ligand binds to the individual RTK receptors, which leads to:
    • Dimerization: 2 neighboring RTKs join together.
    • Autophosphorylation:
      • The dimers phosphorylate each other.
      • 1 RTK monomer transfers a phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes group from adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs triphosphate (ATP) to the other RTK monomer (now known as phosphotyrosines).
  • Phosphotyrosines act as docking sites for other proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis involved in the signal transduction Transduction The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a gene transfer technique. Bacteriology cascade.
  • The cellular response of the RTK activation depends on the downstream proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis that are present.
  • The advantage of a kinase cascade is that a small external signal can be amplified many times inside the cell.
  • Dysfunction of this cascade can lead to cancer due to failure to control general cellular function.
Receptor tyrosine kinase function

Receptor tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinase (RTK) function:
When a ligand binds to the extracellular domain of the RTK, 2 RTKs come together in a process known as dimerization. Once dimerized, each RTK transfers a phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes group from adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs triphosphate (ATP) to its partner in a process known as autophosphorylation. After autophosphorylation, the phosphotyrosines act as docking and activation sites for other proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, which are usually other enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes. The type of cellular response depends on which additional proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis are present.
Tyr: tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids
P: phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes

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Examples of RTKs

Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin receptors:

  • Mature insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin receptors begin as an inactive dimer, containing 2 alpha and 2 beta subunits that are linked together by disulfide bridges:
    • Alpha subunits: extracellular domains containing the ligand-binding site
    • Beta subunits: transmembrane and intracellular tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinase domains
  • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin binds to RTK alpha domains → triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) rapid autophosphorylation
  • Signaling pathway:
    • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin response substrate Substrate A substance upon which the enzyme acts. Basics of Enzymes 1 (IRS-1) binds to the phosphotyrosines → 
    • Activates phosphatidylinositol (PI3) kinase → 
    • Results in phosphatidylinositol (3,4,5)-trisphosphate (PIP3) formation → 
    • PIP3 activates 3-phosphoinositide-dependent protein kinase Protein kinase A family of enzymes that catalyze the conversion of ATP and a protein to adp and a phosphoprotein. Interferons 1 (PDK1), which activates Akt kinase → 
    • Causes the translocation of glucose transporter 4 Glucose transporter 4 A glucose transport protein found in mature muscle cells and adipocytes. It promotes transport of glucose from the blood into target tissues. The inactive form of the protein is localized in cytoplasmic vesicles. In response to insulin, it is translocated to the plasma membrane where it facilitates glucose uptake. Digestion and Absorption of Carbohydrates (GLUT4) (a protein channel that allows glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance into the cell) to the plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products membrane → 
    • Glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance can enter the cell
  • Another insulin-signaling pathway results in increased transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription and translation Translation Translation is the process of synthesizing a protein from a messenger RNA (mRNA) transcript. This process is divided into three primary stages: initiation, elongation, and termination. Translation is catalyzed by structures known as ribosomes, which are large complexes of proteins and ribosomal RNA (rRNA). Stages and Regulation of Translation of glycogen synthase Glycogen synthase An enzyme that catalyzes the transfer of d-glucose from udp glucose into 1, 4-alpha-d-glucosyl chains. Glycogen Metabolism (GS) → ↑ conversion of glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance to glycogen within the cell
The insulin receptor, an rtk

The insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin receptor, a receptor tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinase (RTK):
When insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin binds, the insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin response protein triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) a phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing cascade, ultimately resulting in the activation of glycogen synthase Glycogen synthase An enzyme that catalyzes the transfer of d-glucose from udp glucose into 1, 4-alpha-d-glucosyl chains. Glycogen Metabolism (GS), which converts the extra glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance into glycogen.

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Epidermal growth factor receptors (EGFRs) and the RAS RAS Renal artery stenosis (RAS) is the narrowing of one or both renal arteries, usually caused by atherosclerotic disease or by fibromuscular dysplasia. If the stenosis is severe enough, the stenosis causes decreased renal blood flow, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to renovascular hypertension (RVH). Renal Artery Stenosis signaling pathway:

  • Epidermal growth factor (EGF) binds to EGFRs → causes dimerization and autophosphorylation
  • A signaling complex of proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis assembles on the phosphotyrosines.
  • This signaling complex transfers a phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes group from guanosine trisphosphate (GTP) to RAS RAS Renal artery stenosis (RAS) is the narrowing of one or both renal arteries, usually caused by atherosclerotic disease or by fibromuscular dysplasia. If the stenosis is severe enough, the stenosis causes decreased renal blood flow, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to renovascular hypertension (RVH). Renal Artery Stenosis guanosine diphosphate (RAS-GDP), resulting in RAS-GTP, which is the active form of RAS RAS Renal artery stenosis (RAS) is the narrowing of one or both renal arteries, usually caused by atherosclerotic disease or by fibromuscular dysplasia. If the stenosis is severe enough, the stenosis causes decreased renal blood flow, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to renovascular hypertension (RVH). Renal Artery Stenosis.
  • RAS RAS Renal artery stenosis (RAS) is the narrowing of one or both renal arteries, usually caused by atherosclerotic disease or by fibromuscular dysplasia. If the stenosis is severe enough, the stenosis causes decreased renal blood flow, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to renovascular hypertension (RVH). Renal Artery Stenosis signaling pathway:
    • RAS-GTP → activates RAF kinase → activates MEK kinase → activates MAP kinase (MAPK)
    • MAPK activates MNK and RSK, which phosphorylate specific transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription factors required for cell division Cell Division A type of cell nucleus division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. Cell Cycle.
  • RAS RAS Renal artery stenosis (RAS) is the narrowing of one or both renal arteries, usually caused by atherosclerotic disease or by fibromuscular dysplasia. If the stenosis is severe enough, the stenosis causes decreased renal blood flow, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to renovascular hypertension (RVH). Renal Artery Stenosis itself is a slow GTPase:
    • RAS-GTP will slowly cleave off a phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes group, inactivating itself back to RAS-GDP.
    • Point mutations can remove its GTPase activity, resulting in RAS RAS Renal artery stenosis (RAS) is the narrowing of one or both renal arteries, usually caused by atherosclerotic disease or by fibromuscular dysplasia. If the stenosis is severe enough, the stenosis causes decreased renal blood flow, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to renovascular hypertension (RVH). Renal Artery Stenosis that is perpetually activated → promotes continued cell division Cell Division A type of cell nucleus division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. Cell Cycle
    • RAS RAS Renal artery stenosis (RAS) is the narrowing of one or both renal arteries, usually caused by atherosclerotic disease or by fibromuscular dysplasia. If the stenosis is severe enough, the stenosis causes decreased renal blood flow, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to renovascular hypertension (RVH). Renal Artery Stenosis mutations are indicated in multiple human cancers.

Examples of clinical relevance

Abnormalities in RTKs are known to cause a number of different congenital Congenital Chorioretinitis malformation syndromes and cancers, especially with gain of function mutations causing excessive cell division Cell Division A type of cell nucleus division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. Cell Cycle. Some examples include:

  • Chronic myeloid leukemia Chronic myeloid leukemia Chronic myeloid leukemia is a malignant proliferation of the granulocytic cell line characterized by a fairly normal differentiation. The underlying genetic abnormality is the Philadelphia chromosome, an abbreviated chromosome 22, resulting from reciprocal (9;22)(q34;q11) translocation. Chronic Myeloid Leukemia ( CML CML Chronic myeloid leukemia is a malignant proliferation of the granulocytic cell line characterized by a fairly normal differentiation. The underlying genetic abnormality is the Philadelphia chromosome, an abbreviated chromosome 22, resulting from reciprocal (9;22)(q34;q11) translocation. Chronic Myeloid Leukemia): a malignant proliferation of the granulocytic cell line due to a reciprocal translocation (9;22)(q34;q11). The chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics contains a BCR-ABL1 fusion gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (from ABL1 on chromosome 9 Chromosome 9 Friedreich’s Ataxia and BCR BCR Lymphocytes: Histology on chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 22), which produces constitutively active tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinases Kinases Macrolides and Ketolides and, consequently, uncontrolled granulocytic production. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can be asymptomatic or have constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis, sternal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly
  • Achondroplasia: an autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types dysplasia due to gain of function mutations in the fibroblast growth factor Fibroblast growth factor A family of small polypeptide growth factors that share several common features including a strong affinity for heparin, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family. X-linked Hypophosphatemic Rickets receptor 3 (FGFR3) gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics, which codes for an RTK. As a result, the FGFR3 receptor is permanently activated, inhibiting chondrocyte proliferation, which results in impaired bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types formation and skeletal anomalies.

G-protein-coupled Receptors

Overview

G-protein-coupled receptors (GPCRs) are transmembrane proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis that bind BIND Hyperbilirubinemia of the Newborn hormone ligands on their extracellular side, which induces a conformational change inside the cell, activating an associated G protein, which then triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) a signaling cascade via 2nd messengers.

  • Largest family of receptors, with over 800 GPCR genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure identified
  • Often involved in metabolic and structural changes within a cell
  • Examples:
    • Beta-adrenergic receptors
    • Many olfactory receptors

Structure

  • Extracellular domain: contains the ligand-binding sites 
  • Transmembrane domain:
    • Anchors the receptor in the PM
    • Often composed of 7 alpha helices (known as seven-transmembrane (7TM) receptors)
  • Intracellular domain: bound to a G protein
  • G proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis:
    • Proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis that bind BIND Hyperbilirubinemia of the Newborn to guanine Guanine Nucleic Acids nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids (GTP and GDP)
    • Consist of 3 subunits: alpha, beta, and gamma  
    • Alpha subunit: 
      • Binds the guanine Guanine Nucleic Acids nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids: GTP (active state) and GDP (inactive state)
      • Slowly hydrolyzes GTP to GDP → once activated by GTP, the alpha subunit will eventually inactivate itself through hydrolytic conversion to GDP
    • Beta and gamma: help the alpha‒GDP associate with the GPCR  
Diagram depicting a g-protein coupled receptor (gpcr) bound to a g-protein

Diagram depicting a G-protein-coupled receptor (GPCR) bound to a G protein:
The G proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis consist of 3 subunits: alpha (which binds to guanosine diphosphate (GDP) in its inactive form and guanosine triphosphate (GTP) in its active form), beta, and gamma (which helps the alpha subunit associate with the GPCR).

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Activation pathway

  • Ligand binds to its binding site on the external portion of the receptor → induces a conformational change in the GPCR
  • This causes phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing of the GDP bound to the alpha subunit → becomes alpha‒GTP (activated G protein)
  • Alpha‒GTP separates from the beta and gamma subunit → goes and phosphorylates the next protein in the signaling cascade known as the effector protein
  • Effector proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis:
    • Enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes, often membrane bound
    • Phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing may be activating or inactivating
    • Frequently generate 2nd messengers
Activation pathway for g-protein-coupled receptors (gpcrs)

Activation pathway for G-protein-coupled receptors (GPCRs):
A ligand binds to the GPCR, inducing a conformational change internally. This conformational change causes the alpha subunit of the G protein to exchange a guanosine diphosphate (GDP) for a guanosine triphosphate (GTP), which activates the G protein. The GTP-bound alpha subunit separates from the beta and gamma subunits and goes to activate an effector enzyme (via phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing from the GTP). The effector enzyme then activates a 2nd messenger (here cyclic adenosine monophosphate Adenosine monophosphate Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2′-, 3′-, or 5′-position. Purine and Pyrimidine Metabolism ( cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors)), which relays the signal inside the cell.

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Adenylate cyclase (AC) and the cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors 2nd messenger system

Adenylate cyclase (also called adenylyl cyclase) is a common GPCR effector protein. An activated G protein phosphorylates AC, activating it to convert ATP to cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors, a common 2nd messenger.

Example 1: Glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions pathway

  • Glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions binds its receptor, which is a GPCR → conformational change
  • The alpha subunit of the G protein bound to the internal surface of the GPCR exchanges GDP for GTP and separates from the beta and gamma subunits.
  • Alpha‒GTP (active form) phosphorylates AC, activating it.
  • AC generates cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors from ATP.
  • cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors phosphorylates the regulatory subunits of protein kinase A Protein kinase A A group of enzymes that are dependent on cyclic amp and catalyze the phosphorylation of serine or threonine residues on proteins. Included under this category are two cyclic-amp-dependent protein kinase subtypes, each of which is defined by its subunit composition. Glycogen Metabolism (PKA) → this causes the regulatory subunits to disassociate from the catalytic subunits, thus “activating” the PKA
  • PKA phosphorylates:
    • GS, inactivating it → glycogen synthesis Synthesis Polymerase Chain Reaction (PCR) stops
    • Phosphorylase kinase (PK), activating it → PK activates glycogen phosphorylase Glycogen phosphorylase An enzyme that catalyzes the degradation of glycogen in animals by releasing glucose-1-phosphate from the terminal alpha-1, 4-glycosidic bond. This enzyme exists in two forms: an active phosphorylated form ( phosphorylase A) and an inactive un-phosphorylated form (phosphorylase B). Both A and B forms of phosphorylase exist as homodimers. In mammals, the major isozymes of glycogen phosphorylase are found in muscle, liver and brain tissue. Glycogen Metabolism → stimulates the breakdown of glycogen
  • Summary: Glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions stimulates the breakdown of glycogen to glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance and simultaneously inhibits glycogen synthesis Synthesis Polymerase Chain Reaction (PCR).
G-protein coupled receptor (gpcr)

G-protein-coupled receptor (GPCR) that is coupled to adenylate cyclase (AC):
Note active enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes are shown in green while inactive enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes are shown in red. The AC converts adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs triphosphate (ATP) to cyclic adenosine monophosphate Adenosine monophosphate Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2′-, 3′-, or 5′-position. Purine and Pyrimidine Metabolism ( cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors), which then activates protein kinase A Protein kinase A A group of enzymes that are dependent on cyclic amp and catalyze the phosphorylation of serine or threonine residues on proteins. Included under this category are two cyclic-amp-dependent protein kinase subtypes, each of which is defined by its subunit composition. Glycogen Metabolism (PKA). PKA then phosphorylates both glycogen synthase Glycogen synthase An enzyme that catalyzes the transfer of d-glucose from udp glucose into 1, 4-alpha-d-glucosyl chains. Glycogen Metabolism (GS), inactivating the GS, and phosphorylase kinase (PK), activating the PK. Activated PK then activates glycogen phosphorylase Glycogen phosphorylase An enzyme that catalyzes the degradation of glycogen in animals by releasing glucose-1-phosphate from the terminal alpha-1, 4-glycosidic bond. This enzyme exists in two forms: an active phosphorylated form ( phosphorylase A) and an inactive un-phosphorylated form (phosphorylase B). Both A and B forms of phosphorylase exist as homodimers. In mammals, the major isozymes of glycogen phosphorylase are found in muscle, liver and brain tissue. Glycogen Metabolism, which stimulates the breakdown of glycogen to glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance.
GTP: guanosine-5′-triphosphate
GDP: guanosine diphosphate
ATP: adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs triphosphate
cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors: cyclic adenosine monophosphate Adenosine monophosphate Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2′-, 3′-, or 5′-position. Purine and Pyrimidine Metabolism

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Example 2: Epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs pathways (1 molecule having different effects depending on the proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis present in the target cell)

  • In skeletal muscle: epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs binds to a GPCR, which activates AC in an identical fashion to glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions → ↑ glycogen breakdown into glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance
  • In cardiac muscle Cardiac muscle The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Muscle Tissue: Histology: the cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors produced by AC results in ↑ contraction strength
  • In intestines: epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs binds to a GPCR which inhibits AC, causing relaxation of intestinal muscles and slowing of digestion Digestion Digestion refers to the process of the mechanical and chemical breakdown of food into smaller particles, which can then be absorbed and utilized by the body. Digestion and Absorption
Two different g proteins activating the same internal signal transduction pathway

Two different G proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis can activate the same internal signal transduction Transduction The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a gene transfer technique. Bacteriology pathway:
Here, epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs and glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions can both activate glycogen breakdown into glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance.
GPCR: G-protein-coupled receptors
cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors: cyclic adenosine monophosphate Adenosine monophosphate Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2′-, 3′-, or 5′-position. Purine and Pyrimidine Metabolism
PKA: protein kinase A Protein kinase A A group of enzymes that are dependent on cyclic amp and catalyze the phosphorylation of serine or threonine residues on proteins. Included under this category are two cyclic-amp-dependent protein kinase subtypes, each of which is defined by its subunit composition. Glycogen Metabolism

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Phospholipase C Phospholipase C A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of glycerophospholipids. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of phosphatidylcholine, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of phosphatidylinositols. Pseudomonas (PLC) (effector protein) and 2nd messengers IP3 and DAG DAG Second Messengers

  • Ligand binds GPCR → conformational change
  • The alpha subunit of the G protein exchanges GDP for GTP and separates from the beta and gamma subunits.
  • Alpha‒GTP (active) phosphorylates PLC, activating it.
  • PLC cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into IP3 and DAG DAG Second Messengers.
  • IP3 travels to the ER and binds to a ligand-gated ion channel, causing that channel to open and release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) into the cytoplasm.
  • Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)2+ then:
    • Exerts a cellular response 
    • Causes DAG DAG Second Messengers to activate protein kinase Protein kinase A family of enzymes that catalyze the conversion of ATP and a protein to adp and a phosphoprotein. Interferons C (PKC), which goes on to phosphorylate additional proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
  • E.g., in parietal Parietal One of a pair of irregularly shaped quadrilateral bones situated between the frontal bone and occipital bone, which together form the sides of the cranium. Skull: Anatomy cells in the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy, ACh ACh A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS binds a muscarinic GPCR → activates PLC → generates IP3 and DAG DAG Second Messengers Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)2+ from the ER and DAG DAG Second Messengers both help activate the H+/K+ ATPase, which secretes H+ ions into the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy lumen
G-protein-coupled receptor (gpcr) activates phospholipase c (plc)

A G-protein-coupled receptor (GPCR) activates phospholipase C Phospholipase C A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of glycerophospholipids. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of phosphatidylcholine, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of phosphatidylinositols. Pseudomonas (PLC), which converts phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol triphosphate ( IP3 IP3 Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4, 5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1, 4, 5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell’s endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. Second Messengers) and diacylglycerol Diacylglycerol Second Messengers ( DAG DAG Second Messengers). The IP3 IP3 Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4, 5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1, 4, 5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell’s endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. Second Messengers then binds to a ligand-gated ion channel on the ER, causing the channel to open and Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) to efflux into the cytoplasm, causing a cellular response (e.g., triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) hormone release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology from endocrine cells).
GTP: guanosine-5′-triphosphate
GDP: guanosine diphosphate

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Example of clinical relevance

Over 30 different human diseases can be linked to mutations in GPCRs. These mutations may be activating or inactivating. One example is nephrogenic diabetes insipidus Diabetes Insipidus Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of DI: central DI (CDI) and nephrogenic DI (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus (NDI).

Nephrogenic diabetes insipidus Diabetes Insipidus Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of DI: central DI (CDI) and nephrogenic DI (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus: a disorder caused by abnormalities in the antidiuretic hormone Antidiuretic hormone Antidiuretic hormones released by the neurohypophysis of all vertebrates (structure varies with species) to regulate water balance and osmolarity. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a cystine. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the kidney collecting ducts to increase water reabsorption, increase blood volume and blood pressure. Hypernatremia (ADH) receptor, leading to ADH resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing. The ADH receptor is a GPCR that normally triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) the insertion of aquaporin channels Channels The Cell: Cell Membrane into the membranes of renal collecting duct Collecting duct Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of bellini) which opens on the summit of the papilla. Renal Cell Carcinoma cells, allowing for water reabsorption. With an abnormal receptor, the GPCR ineffectively transmits the ADH signal within the cell, resulting in resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing to ADH and a decreased ability for individuals to concentrate urine.

Nuclear Receptors

Overview

  • A subtype of intracellular receptor
  • Act as ligand-activated transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription factors, which ultimately affect gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics expression
  • Although known as nuclear receptors, they are often found in the cytoplasm, which move to the nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles.

Structure

  • C-terminal ligand-binding region
  • Core DNA-binding domain (DBD), which binds to hormone response elements (HREs) in the DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure
  • Regions that interact with other transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription factors

Activation pathway

  • Ligand binds the intracellular receptor (usually in the cytoplasm).
  • The ligand–receptor complex travels to the nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles (if not already there) to bind BIND Hyperbilirubinemia of the Newborn the HREs in DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure.
  • Interacts with other transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription factors to affect gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics expression (may act as enhancers or repressors)
Nuclear receptor activation pathway

Nuclear receptor activation pathway

Image by Kevin Ahern, edited by Lecturio.

Example of clinical relevance

Complete androgen insensitivity syndrome Androgen insensitivity syndrome Androgen insensitivity syndrome (AIS) is an X-linked recessive condition in which a genetic mutation affects the function of androgen receptors, resulting in complete (CAIS), partial (PAIS), or mild (MAIS) resistance to testosterone. All individuals with AIS have a 46,XY karyotype; however, phenotypes vary and include phenotypic female, virilized female, undervirilized male, and phenotypic male individuals. Androgen Insensitivity Syndrome ( AIS AIS Scoliosis): an X-linked recessive X-Linked Recessive Duchenne Muscular Dystrophy condition in which a genetic mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations affects the function of androgen receptors, leading to testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing. The androgen receptors are nuclear receptors, located in the cytoplasm, which move into the nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles when bound to androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens and increase the transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription of proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis that cause androgenic effects. With abnormal receptors, individuals will have a 46,XY karyotype Karyotype The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. Congenital Malformations of the Female Reproductive System and undescended testes Testes Gonadal Hormones, with external female genitalia and breast development (due to peripheral conversion of the excess testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens to estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy).

References

  1. Miller, EJ. (2021). Physiology, cellular receptor. StatPearls. Retrieved October 26, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK554403/
  2. Robertson, A. (2021). Cellular receptors. TeachMePhysiology. Retrieved October 26, 2021, from https://teachmephysiology.com/biochemistry/molecules-and-signalling/cellular-receptors/
  3. Lemmon, MA, & Schlessinger, J. (2010, June 25). Cell signaling by receptor tyrosine kinases. Cell. Retrieved October 26, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2914105/#:~:text=All%20RTKs%20have%20a%20similar,terminal%20and%20juxtamembrane%20regulatory%20regions
  4. O’Shea, JJ., et al. (2015). The Jak-STAT pathway: Impact on human disease and therapeutic intervention. Annual Review of Medicine. Retrieved October 26, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634336/
  5. Bartee, L, Shriner, W, & Creech, C. (n.d.). Types of receptors. Principles of Biology. Retrieved October 26, 2021, from https://openoregon.pressbooks.pub/mhccmajorsbio/chapter/types-of-receptors/
  6. Schöneberg T, et al. (2004). Mutant G-protein-coupled receptors as a cause of human diseases. Pharmacol Ther. 104(3), pp. 173–206. https://doi.org/10.1016/j.pharmthera.2004.08.008
  7. McDonell, LM, Kernohan, KD, Boycott, KM., & Sawyer, SL. (2015). Receptor tyrosine kinase mutations in developmental syndromes and cancer: Two sides of the same coin. Human Molecular Genetics, 24(R1), R60–R66. https://doi.org/10.1093/hmg/ddv254

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