Achieve Mastery of Medical Concepts

Study for medical school and boards with Lecturio

Synthesis of Nonessential Amino Acids

An essential amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids is an amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids that must come from the diet. Alternatively, a nonessential amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids can be produced by cells and does not require dietary intake. Various substrates undergo a series of processes to make amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance. There are 11 amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance that can be completely synthesized; the other 9 are considered essential and must be included in an individual’s diet. Nonessential amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance are alanine, arginine Arginine An essential amino acid that is physiologically active in the l-form. Urea Cycle, asparagine, aspartic acid, cysteine, glutamic acid Glutamic acid A non-essential amino acid naturally occurring in the l-form. Glutamic acid is the most common excitatory neurotransmitter in the central nervous system. Urea Cycle, glutamine, glycine, proline, serine, and tyrosine. Deficiency in the 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 required for amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids metabolism lead to serious conditions that often present early in life, such as maple syrup urine disease Maple syrup urine disease An autosomal recessive inherited disorder with multiple forms of phenotypic expression, caused by a defect in the oxidative decarboxylation of branched-chain amino acids. These metabolites accumulate in body fluids and render a 'maple syrup' odor. The disease is divided into classic, intermediate, intermittent, and thiamine responsive subtypes. The classic form presents in the first week of life with ketoacidosis, hypoglycemia, emesis, neonatal seizures, and hypertonia. The intermediate and intermittent forms present in childhood or later with acute episodes of ataxia and vomiting. Disorders of Amino Acid Metabolism and phenylketonuria.

Last updated: 6 May, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance are building blocks for 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 and metabolic intermediates for reactions. Amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance are classified as essential or nonessential. Essential amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance must be incorporated into the diet because the body cannot produce them at sufficient levels to meet physiologic demands; nonessential amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance can be produced by the body. 

  • Essential amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance include: 
    • Phenylalanine
    • Valine
    • Threonine
    • Tryptophan
    • Methionine
    • Leucine
    • Isoleucine
    • Lysine
    • Histidine
  • Nonessential amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance include:
    • Alanine
    • Arginine Arginine An essential amino acid that is physiologically active in the l-form. Urea Cycle
    • Asparagine
    • Aspartic acid (aspartate)
    • Cysteine
    • Glutamine
    • Glutamic acid Glutamic acid A non-essential amino acid naturally occurring in the l-form. Glutamic acid is the most common excitatory neurotransmitter in the central nervous system. Urea Cycle (glutamate)
    • Glycine
    • Proline
    • Serine
    • Tyrosine
  • Amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids synthesis Synthesis Polymerase Chain Reaction (PCR) reactions can be grouped by biosynthetic families, named according to their common starting metabolite.

Biosynthetic families

Table: Comparison of biosynthetic families
Biosynthetic family Amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids Catabolic product Product A molecule created by the enzymatic reaction. Basics of Enzymes
α-Ketoglutarate Glutamate Glucogenic AA AA Amyloidosis
Glutamine Glucogenic AA AA Amyloidosis
Proline Glucogenic AA AA Amyloidosis
Arginine Arginine An essential amino acid that is physiologically active in the l-form. Urea Cycle Glucogenic AA AA Amyloidosis
3-Phosphoglycerate 3-phosphoglycerate Glycolysis Serine Glucogenic AA AA Amyloidosis
Glycine Glucogenic AA AA Amyloidosis
Cysteine Glucogenic AA AA Amyloidosis
Oxaloacetate Oxaloacetate Derivatives of oxaloacetic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include a 2-keto-1, 4-carboxy aliphatic structure. Citric Acid Cycle Aspartate Glucogenic AA AA Amyloidosis
Asparagine Glucogenic AA AA Amyloidosis
Methionine* Glucogenic AA AA Amyloidosis
Threonine* Ketogenic or glucogenic AA AA Amyloidosis
Lysine* Ketogenic AA AA Amyloidosis
Isoleucine* Ketogenic or glucogenic AA AA Amyloidosis
Pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis Alanine Glucogenic AA AA Amyloidosis
Valine* Glucogenic AA AA Amyloidosis
Leucine* Ketogenic AA AA Amyloidosis
Phosphoenolpyruvate Phosphoenolpyruvate A monocarboxylic acid anion derived from selective deprotonation of the carboxy group of phosphoenolpyruvic acid. It is a metabolic intermediate in glycolysis; gluconeogenesis; and other pathways. Glycolysis & erythrose 4-phosphate Tryptophan* Ketogenic or glucogenic AA AA Amyloidosis
Phenylalanine* Ketogenic or glucogenic AA AA Amyloidosis
Tyrosine Ketogenic or glucogenic AA AA Amyloidosis
*Essential amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance that must be incorporated into the diet. Production of these amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance commonly occurs in prokaryotic Prokaryotic Prokaryotes are unicellular organisms that include 2 of the 3 domains of life: bacteria and archaea. Prokaryotic cells consist of a single cytoplasm-filled compartment enclosed by a cell membrane and cell wall. Cell Types: Eukaryotic versus Prokaryotic organisms and plants Plants Cell Types: Eukaryotic versus Prokaryotic.
AA AA Amyloidosis: amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids
Amino acid biosynthesis synthesis of nonessential amino acids

Amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids biosynthesis Biosynthesis The biosynthesis of peptides and proteins on ribosomes, directed by messenger RNA, via transfer RNA that is charged with standard proteinogenic amino acids. Virology overview
CoA: coenzyme A

Image by Lecturio. License: CC BY-NC-SA 4.0

α-Ketoglutarate Biosynthetic Family

Overview

  • Glutamate, glutamine, proline, and arginine Arginine An essential amino acid that is physiologically active in the l-form. Urea Cycle are synthesized from α-ketoacids, which are produced by the citric acid cycle Citric acid cycle The citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a cyclic set of reactions that occurs in the mitochondrial matrix. The TCA cycle is the continuation of any metabolic pathway that produces pyruvate, which is converted into its main substrate, acetyl-CoA. Citric Acid Cycle.
    • Transamination Transamination Transamination is the transfer of an amino group from an alpha-AA to an alpha-keto acid, which is an AA with an alpha-keto group (=O) instead of an alpha-amino group (NH2). Catabolism of Amino Acids is an essential reaction in the production of these amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance.
    • The enzyme involved in this reaction is an aminotransferase.
  • Glutamate serves as a precursor for the production of many amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance, such as glutamine, proline, and arginine Arginine An essential amino acid that is physiologically active in the l-form. Urea Cycle.
    • α-ketoacid + glutamate ⇄ amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids + α-ketoglutarate
    • Glutamate itself is formed by amination of α-ketoglutarate: α-ketoglutarate + NH4+ ⇄ glutamate

Glutamate synthesis Synthesis Polymerase Chain Reaction (PCR)

Glutamate is produced from α-ketoglutarate through the process of amination.

  • α-ketoglutarate + NH4+ ⇄ glutamate
  • Glutamate serves as the primary precursor for glutamine, proline, and arginine Arginine An essential amino acid that is physiologically active in the l-form. Urea Cycle.

Glutamine synthesis Synthesis Polymerase Chain Reaction (PCR)

Glutamate serves as the precursor for glutamine.

  • Glutamate is converted to glutamine by glutamine synthetase.
  • Glutamine synthetase uses:
    • ATP
    • NH4+: helps prevent ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance build-up
  • Glutamine synthetase inhibitors:
    • Amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance: glycine, alanine, serine, histidine, tryptophan
    • 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: AMP, cytidine triphosphate ( CTP CTP Purine and Pyrimidine Metabolism)
    • Other: carbamoyl phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes, glucosamine-6-phosphate
    • These inhibitors rely on glutamine for production, providing negative feedback Negative feedback Hypothalamic and Pituitary Hormones when glutamine levels are high.
  • Glutamine synthetase activation: 
    • Glutamine synthetase is active in the deadenylated form.
    • Adenylyl transferase is responsible for adenylation and deadenylation.
Glutamine synthesis

Glutamine synthesis Synthesis Polymerase Chain Reaction (PCR) is mediated by glutamine synthetase:
This reaction requires ATP.

Image by Lecturio. License: CC BY-NC-SA 4.0

Proline synthesis Synthesis Polymerase Chain Reaction (PCR)

Glutamate also serves as the precursor for proline. 

3 steps to produce proline from glutamate:

  1. 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
    • Catalyzed by glutamate-5-kinase and glutamate-5-semialdehyde dehydrogenase 
    • Requires ATP and nicotinamide adenine Adenine A purine base and a fundamental unit of adenine nucleotides. Nucleic Acids dinucleotide (NADH)
    • Produces glutamate-5-semialdehyde
  2. Oxidation and dephosphorylation: 
    • Spontaneous cyclization reaction
    • Produces 1-pyrroline-5-carboxylic acid
  3. Reduction: 
    • Catalyzed by pyrroline-5-carboxylate reductase
    • Requires NADH
    • Generates proline
Reactions contributing to proline synthesis

Cyclization and reduction reactions contributing to proline synthesis Synthesis Polymerase Chain Reaction (PCR):
These steps require ATP, NADH, and a cyclization intermediate.

Image by Lecturio. License: CC BY-NC-SA 4.0

Arginine Arginine An essential amino acid that is physiologically active in the l-form. Urea Cycle synthesis Synthesis Polymerase Chain Reaction (PCR)

Arginine Arginine An essential amino acid that is physiologically active in the l-form. Urea Cycle is also derived from glutamate.

4 pathways to make arginine Arginine An essential amino acid that is physiologically active in the l-form. Urea Cycle:

  1. Reversible 2-step reaction
    • From citrulline Citrulline Urea Cycle, aspartate, and ATP
    • Argininosuccinate Argininosuccinate This amino acid is formed during the urea cycle from citrulline, aspartate and ATP. This reaction is catalyzed by argininosuccinic acid synthetase. Urea Cycle serves as an intermediate compound.
  2. Reversible demethylation from asymmetric dimethylarginine (ADMA)
  3. Reversible reaction from ornithine Ornithine An amino acid produced in the urea cycle by the splitting off of urea from arginine. Urea Cycle and urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle
  4. Reversible reaction from citrulline Citrulline Urea Cycle, nitric oxide Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from arginine by nitric oxide synthase. Nitric oxide is one of the endothelium-dependent relaxing factors released by the vascular endothelium and mediates vasodilation. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic gmp. Pulmonary Hypertension Drugs, and nicotinamide adenine Adenine A purine base and a fundamental unit of adenine nucleotides. Nucleic Acids dinucleotide (NADP+)
The 4 ways to produce arginine

The 4 ways to produce arginine Arginine An essential amino acid that is physiologically active in the l-form. Urea Cycle
ADMA: asymmetric dimethylarginine
NADPH NADPH Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5′-phosphate (nmn) coupled by pyrophosphate linkage to the 5′-phosphate adenosine 2. Pentose Phosphate Pathway and NADP+: nicotinamide adenine Adenine A purine base and a fundamental unit of adenine nucleotides. Nucleic Acids dinucleotide
Pi: inorganic phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes

Image by Lecturio. License: CC BY-NC-SA 4.0

3-Phosphoglycerate Biosynthetic Family

Serine, glycine, and cysteine are amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance included in the 3-phosphoglycerate 3-phosphoglycerate Glycolysis (3-PG) biosynthetic family. Serine is the first amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids produced in this group, and it subsequently contributes to the production of glycine and cysteine.

Serine

Produced by a 3-step pathway:

  1. Oxidation of 3-phosphoglycerate 3-phosphoglycerate Glycolysis 
    • Catalyzed by phosphoglycerate dehydrogenase
    • Produces 3-phosphohydroxypyruvate
    • Inhibited by high concentrations of serine
  2. Transamination Transamination Transamination is the transfer of an amino group from an alpha-AA to an alpha-keto acid, which is an AA with an alpha-keto group (=O) instead of an alpha-amino group (NH2). Catabolism of Amino Acids of 3-phosphohydroxypyruvate
    • Catalyzed by phosphoserine transaminase Transaminase A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Catabolism of Amino Acids
    • Produces O-phosphoserine
  3. Hydrolysis Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water. Proteins and Peptides of O-phosphoserine
    • Catalyzed by phosphoserine phosphatase
    • Produces serine
Serine is made via 3 reactions

Serine is made via 3 reactions, beginning with 3-phosphoglycerate 3-phosphoglycerate Glycolysis (PG) and nicotinamide adenine Adenine A purine base and a fundamental unit of adenine nucleotides. Nucleic Acids dinucleotide ( NAD NAD A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway+)

Image by Lecturio. License: CC BY-NC-SA 4.0

Glycine

Glycine is produced from serine with the removal of a hydroxymethyl group.

Glycine is produced from serine

Glycine is produced from serine:
This 1-step reaction depends on the removal of a hydroxymethyl group.

Image by Lecturio. License: CC BY-NC-SA 4.0

Cysteine

Cysteine is produced from serine and homocysteine through a 2-step pathway:

  1. Homocysteine and serine combine to form cystathionine
    • Catalyzed by cystathionine beta-synthase
    • Homocysteine contributes sulfur group
  2. Cystathionine converted to cysteine
    • Catalyzed by cystathionine gamma-lyase
    • Also produces α-ketobutyrate
Formation of cysteine from serine and homocysteine

The formation of cysteine from serine and homocysteine

Image: “Cysteine biosynthesis Biosynthesis The biosynthesis of peptides and proteins on ribosomes, directed by messenger RNA, via transfer RNA that is charged with standard proteinogenic amino acids. Virology” by David E. License: Public Domain

Oxaloacetate Biosynthetic Family

Overview

Aspartate, lysine, threonine, asparagine, methionine, and isoleucine are amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance that have oxaloacetate Oxaloacetate Derivatives of oxaloacetic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include a 2-keto-1, 4-carboxy aliphatic structure. Citric Acid Cycle as a common precursor.

  • Aspartate and asparagine are the only nonessential amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance in this family.
  • Oxaloacetate Oxaloacetate Derivatives of oxaloacetic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include a 2-keto-1, 4-carboxy aliphatic structure. Citric Acid Cycle is first converted to aspartate.
  • Aspartate is then converted to asparagine.

Aspartate

Aspartate is produced by a transamination Transamination Transamination is the transfer of an amino group from an alpha-AA to an alpha-keto acid, which is an AA with an alpha-keto group (=O) instead of an alpha-amino group (NH2). Catabolism of Amino Acids reaction.

  • Catalyzed by an aminotransferase: transfers an amine group from another amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids
  • Produces aspartate from oxaloacetate Oxaloacetate Derivatives of oxaloacetic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include a 2-keto-1, 4-carboxy aliphatic structure. Citric Acid Cycle

Asparagine

Asparagine is also produced by a transamination Transamination Transamination is the transfer of an amino group from an alpha-AA to an alpha-keto acid, which is an AA with an alpha-keto group (=O) instead of an alpha-amino group (NH2). Catabolism of Amino Acids reaction.

  • Catalyzed by asparagine synthetase 
  • Produces asparagine from aspartate

Pyruvate Biosynthetic Family

Overview

Alanine, valine, and leucine share pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis as a common precursor. Alanine is the only amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids in the pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis biosynthetic family that can be produced by humans.

  • Pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis is an end product Product A molecule created by the enzymatic reaction. Basics of Enzymes of glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis.
  • Feedback inhibition is provided by the final product Product A molecule created by the enzymatic reaction. Basics of Enzymes (e.g., alanine).

Alanine

Alanine is produced through a 2-step reaction. 

  1. α-ketoglutarate is converted to glutamate:
    • Catalyzed by glutamate dehydrogenase
    • Requires ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance and NADH
  2. Glutamate transfers an amino group to pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis to form alanine:
    • Catalyzed by an aminotransferase enzyme Aminotransferase enzyme A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Catabolism of Amino Acids
    • Requires preformed pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis from glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis

Phosphoenolpyruvate Biosynthetic Family

Overview

The aromatic amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance phenylalanine, tryptophan, and tyrosine are included in the phosphoenolpyruvate Phosphoenolpyruvate A monocarboxylic acid anion derived from selective deprotonation of the carboxy group of phosphoenolpyruvic acid. It is a metabolic intermediate in glycolysis; gluconeogenesis; and other pathways. Glycolysis family. Phenylalanine and tryptophan are essential amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance; tyrosine is a nonessential amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids.

Tyrosine

Phenylalanine serves as the precursor for tyrosine

  • The reaction is catalyzed by biopterin-dependent phenylalanine hydroxylase.
  • Phenylalanine hydroxylase deficiency results in phenylketonuria.
  • Tyrosine is the precursor for important neurotransmitters:
    • Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS
    • Noradrenaline
    • Adrenaline
The conversion of l-phenylalanine into l-tyrosine

The conversion of L-phenylalanine into L-tyrosine is the 1st step in the upper left.
Tyrosine and phenylalanine are precursors to a number of crucial neurotransmitters and 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.

Image by Lecturio. License: CC BY-NC-SA 4.0

Clinical Relevance

  • Phenylketonuria (PKU): defect of phenylalanine hydroxylase that results in impairment of the conversion of phenylalanine to tyrosine and subsequent accumulation of phenylalanine. Individuals will present with psychomotor delay and seizures, and their sweat will classically have a “mousy” odor. It is critical for these individuals to avoid ingestion of phenylalanine.
  • Maple syrup urine disease Maple syrup urine disease An autosomal recessive inherited disorder with multiple forms of phenotypic expression, caused by a defect in the oxidative decarboxylation of branched-chain amino acids. These metabolites accumulate in body fluids and render a ‘maple syrup’ odor. The disease is divided into classic, intermediate, intermittent, and thiamine responsive subtypes. The classic form presents in the first week of life with ketoacidosis, hypoglycemia, emesis, neonatal seizures, and hypertonia. The intermediate and intermittent forms present in childhood or later with acute episodes of ataxia and vomiting. Disorders of Amino Acid Metabolism: defect in the branched-chain α-ketoacid dehydrogenase complex that results in the accumulation of branched-chain amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance. Individuals present with cognitive disabilities, sweet-smelling urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat, and dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia. The primary treatment is avoidance of branched-chain amino acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance. Severe cases may require a liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy transplant.
  • Homocystinuria: defect in the enzyme cystathionine β-synthase, which leads to an accumulation of homocysteine. Individuals present with flushing, developmental delay, downward lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy dislocation, vascular disease, and osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis. It is recommended that these individuals maintain a diet low in sulfur.
  • Alkaptonuria: deficiency of homogentisic acid dioxygenase, which impairs the normal degradation of tyrosine to fumarate Fumarate Citric Acid Cycle. Individuals present with a bluish-black discoloration of connective tissues, arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis, and calcifications of various tissues. There is currently no treatment for alkaptonuria, but the life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids remains normal in these individuals.

References

  1. Reitzer, L. (2009). Amino acid synthesis. In: Encyclopedia of Microbiology, 3rd ed. Academic Press, pp. 1–17. https://doi.org/10.1016/B978-012373944-5.00063-8.
  2. Rose A. J. (2019). Amino acid nutrition and metabolism in health and disease. Nutrients 11:2623. https://doi.org/10.3390/nu11112623.
  3. Young V.R. (2000). Protein and amino acids. In: Gershwin M.E., German J.B., Keen C.L. (Eds.), Nutrition and Immunology. Totowa, NJ: Humana Press. https://doi.org/10.1007/978-1-59259-709-3_5.
  4. Hou, Y., Wu, G. (2018). Nutritionally essential amino acids. Advances in Nutrition 9:849–851. https://doi.org/10.1093/advances/nmy054

USMLE™ is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). MCAT is a registered trademark of the Association of American Medical Colleges (AAMC). NCLEX®, NCLEX-RN®, and NCLEX-PN® are registered trademarks of the National Council of State Boards of Nursing, Inc (NCSBN®). None of the trademark holders are endorsed by nor affiliated with Lecturio.

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

User Reviews

¡Hola!

Esta página está disponible en Español.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.

Details