Cholesterol is an important lipid molecule that is used for many biologic functions. Cholesterol can either be synthesized from endogenous acetyl-CoA Acetyl-CoA Acetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent. Citric Acid Cycle or absorbed from food in the GI tract. Because cholesterol is lipophilic, it must be transported through the bloodstream via lipoproteins Lipoproteins Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of triglycerides and cholesterol esters surrounded by a layer of hydrophilic free cholesterol; phospholipids; and apolipoproteins. Lipoproteins are classified by their varying buoyant density and sizes. Lipid Metabolism, where it can be picked up by hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy or peripheral tissues. There, cholesterol can be stored, used in cellular membranes, or used as a precursor for steroid 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. The human body cannot degrade cholesterol’s ring structure, so the only mechanism for potential excretion is through the production of bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy 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.
Last updated: 3 Dec, 2021
Cholesterol’s synthesis Synthesis Polymerase Chain Reaction (PCR) pathway overlaps with the synthesis Synthesis Polymerase Chain Reaction (PCR) of ketone bodies Ketone bodies The metabolic substances acetone; 3-hydroxybutyric acid; and acetoacetic acid (acetoacetates). They are produced in the liver and kidney during fatty acids oxidation and used as a source of energy by the heart, muscle and brain. Ketone Body Metabolism. The steps of this process include:
The
synthesis
Synthesis
Polymerase Chain Reaction (PCR) of cholesterol by the mevalonate pathway:
The number of carbons within each chemical structure is noted to the left.
ER:
endoplasmic reticulum
Endoplasmic reticulum
A system of cisternae in the cytoplasm of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (cell membrane) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced; otherwise it is said to be smooth-surfaced.
The Cell: Organelles
HMG-CoA: 3-hydroxy-3-methyl-glutaryl-coenzyme A
PP: pyrophosphatase
Diagram showing the steps of the mevalonate pathway in the
synthesis
Synthesis
Polymerase Chain Reaction (PCR) of the isoprenoid precursors, which are the building blocks of cholesterol:
HMG-CoA: 3-hydroxy-3-methyl-glutaryl-CoA
Diagram showing the steps of the mevalonate pathway from the isoprenoid precursors to lanosterol
Image by Lecturio.Diagram numbering the rest of the steps needed for the
transformation
Transformation
Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome.
Bacteriology of lanosterol into cholesterol:
The image provides a good comparison between the 2 molecules. Note how the cyclical structures are maintained throughout the conversion process.
Cholesterol is a:
Lipoprotein | Cholesterol/ cholesterol ester Cholesterol Ester Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. Lipid Metabolism |
Triglyceride | Protein | Phospholipid |
---|---|---|---|---|
Chylomicrons | 1%/3% | 85% | 2% | 8% |
VLDL | 7%/10% | 55% | 9% | 20% |
IDL | 8%/30% | 26% | 11% | 22% |
LDL | 10%/35% | 10% | 20% | 20% |
HDL | 4%/12% | 5% | 45% | 25% |
Movement of cholesterol throughout the body:
Movement in the blood is highlighted in green.
FFA
FFA
Macular Degeneration: free fatty acid
Mechanism:
Regulation:
Cellular uptake of LDL and regulation:
Within a hepatocyte, LDL can
bind
BIND
Hyperbilirubinemia of the Newborn with LDL
receptors
Receptors
Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.
Receptors, allowing for
endocytosis
Endocytosis
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis.
The Cell: Cell Membrane. LDL is released from the
receptor
Receptor
Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.
Receptors, which returns to the cell surface. The LDL particle is broken down, releasing cholesterol. This cholesterol can down-regulate expression of LDL
receptors
Receptors
Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.
Receptors and inhibit further cholesterol
synthesis
Synthesis
Polymerase Chain Reaction (PCR) and can then either be stored or used (in this case, converted to
bile
Bile
An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.
Gallbladder and Biliary Tract: Anatomy
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).
ACAT: acyl cholesterol acyltransferase, which converts cholesterol to
cholesterol esters
Cholesterol esters
Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis.
Digestion and Absorption
HMG-CoA: 3-hydroxy-3-methyl-glutaryl-coenzyme A
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme secreted by the
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 into the bloodstream that binds to LDL
receptors
Receptors
Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.
Receptors (both inside and outside the hepatocyte) and subsequently promotes LDL
receptor
Receptor
Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.
Receptors
endocytosis
Endocytosis
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis.
The Cell: Cell Membrane for degradation.
LDL-R: LDL
receptor
Receptor
Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.
Receptors
Chemical structures of bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy 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
Image by Lecturio.Overview of the steroidogenesis pathways:
Cholesterol is initially converted to pregnenolone Pregnenolone A 21-carbon steroid, derived from cholesterol and found in steroid hormone-producing tissues. Pregnenolone is the precursor to gonadal steroid hormones and the adrenal corticosteroids. Gonadal Hormones and then to progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones. From there, the pathway diverges, with many potential end products, including 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, mineralocorticoids Mineralocorticoids Mineralocorticoids are a drug class within the corticosteroid family and fludrocortisone is the primary medication within this class. Fludrocortisone is a fluorinated analog of cortisone. The fluorine moiety protects the drug from isoenzyme inactivation in the kidney, allowing it to exert its mineralocorticoid effect. Mineralocorticoids, 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 estrogens.
Image by Lecturio.Diagram showing a simplified version of the synthesis Synthesis Polymerase Chain Reaction (PCR) pathways of steroid 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.
Synthesis
Synthesis
Polymerase Chain Reaction (PCR) location |
Class | Primary hormone | Functions |
---|---|---|---|
Adrenal glands Adrenal Glands The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. Adrenal Glands: Anatomy | 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 | Cortisone Cortisone A naturally occurring glucocorticoid that has been used in replacement therapy for adrenal insufficiency and as an anti-inflammatory agent. Cortisone itself is inactive; it is converted in the liver to the active metabolite hydrocortisone. Glucocorticoids |
|
Mineralocorticoids Mineralocorticoids Mineralocorticoids are a drug class within the corticosteroid family and fludrocortisone is the primary medication within this class. Fludrocortisone is a fluorinated analog of cortisone. The fluorine moiety protects the drug from isoenzyme inactivation in the kidney, allowing it to exert its mineralocorticoid effect. Mineralocorticoids | Aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia |
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Gonads Gonads The gamete-producing glands, ovary or testis. Hormones: Overview and Types | Progestins Progestins Compounds that interact with progesterone receptors in target tissues to bring about the effects similar to those of progesterone. Primary actions of progestins, including natural and synthetic steroids, are on the uterus and the mammary gland in preparation for and in maintenance of pregnancy. Hormonal Contraceptives | Progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones |
|
Estrogens | Estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins | Sexual development, differentiation, and maturation of primary and secondary sex characteristics Secondary sex characteristics Gonadal Hormones | |
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 | 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 |