What is cholesterol?

Cholesterol: The Basics

 

Cholest-5-en-3β-ol (cholesterol) is a biomolecule essential to animals for membrane integrity and biosynthesis of steroid hormones, bile salts, and Vitamin D.  Structurally, cholesterol is a 17 carbon carbocylclic ring with an eight-member chain, branched at C 25 and C 20, attached at C 17 to the carbocyclic ring, a methyl group at C 10, a double bond at C5-C6, and one hydroxyl group attached at C 3.  The carbocyclic ring is a four ring structure that is a modified form of cyclopentenophenanthrene.    The modified cycolophenanthrene ring and hydrocarbon chain produce cholesterol’s highly hydrophobic nature.  The hydroxyl group at C3 is cholesterol’s lone source of hydrophilicy.  The hydrophobic carbocyclic ring portion of cholesterol facilitates cholesterol’s ability to insert into the hydrophobic portion of the cell membrane and stabilize it, as well as serving as the main structure in the synthesis of steroid hormones, bile salts, and Vitamin D.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Steroid Hormone Precursor

 

             A principal role of cholesterol is that of steroid hormone precursor.  The adrenal cortex and gonads (ovaries and testes) modify cholesterol to form the steroid hormones essential for metabolic function.  The hormones created from cholesterol control kidney function, inflammation, and puberty, for example.  To achieve different steroid hormone configurations of varying activities, the substituents attached to the ring structure are modified but not the ring structure.  For example, cleavage at C 22 and oxidation at C 20 to add a ketone group and create pregnenolone, a hormone that can be further modified to form many more steroid hormones by additional manipulation of its substituents attached to the ring structure.

 

Vitamin D Precursor

 

             The human body has the unique ability to utilize cholesterol for the synthesis of Vitamin D, in conjunction with ultra-violet light absorption through the skin.  After oxidation of cholesterol's  C7-C8 bond by 7-dehydrocholesterol reductase and NADP+ , ultra-violet light cleaves the C9-C10 bond to form a secosteroid structure, cholecalciferol (Vitamin D₃).  Cholecalciferol can be further modified to the circulating form, calcidiol, and the active form, calcitriol. Calcitriol increases calcium reabsorption in the kidney for bone formation, and it also increase calcium and phosphate absorption from the intestinal lumen.

 

Bile Acid Precursor

 

             Excretion of cholesterol occurs mainly in bile acid form.  Bile acids are cholesterol derivatives utilized in lipid digestion and excretion.   Cholesterol is modified in hepatocytes to form the primary bile acids cholic acid and chenodeoxycholylic acid.  Converting cholesterol into a bile acid is a four step process:

Epimerization of the 3β-hydroxyl group to 3α-hydroxyl group.

Reducing the C5-C6 double bond.

Addition of hydroxyl groups of C7 in chenodeoxycholic acid or at C7 and C12 in cholic acid.

Elimination of C25, C26, C27 and addition of a carboxylic acid at C24.

 

Taurine and glycine may be conjugated to the bile acids at C24 to form glycholic acid and Taurocholic acid, respectively.  Microorganisms convert primary bile acids into secondary bile acids in the intestine.

 

 

 

 

 

 

 

 

Where does cholesterol come from?

            

             Cholesterol sources include metabolic synthesis and dietary intake.  Dietary sources include eggs and animal fat.  Synthesis of cholesterol in the body occurs mainly in the liver, intestine, adrenal cortex, and gonads.  All 27 carbons of cholesterol are attained from acetate via acetyl CoA.  Acetyl CoA are created by β-oxidation of fatty acids, oxidation of ketogenic amino acids, and pyruvate dehydrogenase reactions.

             The route cholesterol travels through our body when we eat it is called the exogenous pathway. Cholesterol is transported by way of particles called  chylomicrons  from our intestine to our liver.  The pathway used by our body to transport  cholesterol  from the liver to other tissues is known as the endogenous pathway. 

             Cholesterol is synthesized  in our body in the cytosol and endoplasmic reticulum of cells.  The process requires energy.  One of the important enzymes needed in the process of forming cholesterol is called HMG-CoA reductase. This enzyme is the protein that regulates the rate of cholesterol formation.  When cholesterol levels are high HMG-Co reductase activity is decreased by a feedback inhibition reaction.  Many drugs that lower the amount of cholesterol in our body target this enzyme.