1.2.1 Origins of Cholesterol (Animation)

-How is cholesterol derived from circulating lipoproteins (the preferred source)?
-How is cholesterol derived from preformed cholesterol esters in lipid storage
 vacuoles?
-How is cholesterol synthesized de novo from acetyl coenzyme A?
-How is cholesterol synthesis regulated in steroid-producing cells?

 

Cholesterol is an important component of both high density lipoprotein (HDL) and low density lipoprotein (LDL), which are plasma proteins. LDL particles containing cholesterol bind to LDL receptors in the plasma membrane of steroid synthesizing cells, areinternalized by endocytosis and are degraded to yield free cholesterol. Luteinizing hormone (LH) increases LDL uptake in ovarian cells and adreno-corticotropic hormone (ACTH) increases LDL uptake in adrenocortical cells by increasing the number of LDL receptors.

Circulating lipoprotein is the preferred source of cholesterol for steroidogenesis.

Free cholesterol is either used or esterified via the enzyme cholesterol ester synthase, also known as acyl CoA: cholesterol acyl transferase or ACAT, and stored in lipid storage vacuoles in the cell. If a steroidogenic cell requires more cholesterol than is immediately available from uptake of LDL, stored cholesterol esters are de-esterified by the enzyme cholesterol esterase, also known as sterol ester hydrolase. LH stimulates cholesterol esterase in ovarian cells and ACTH stimulates the enzyme in adrenocortical cells.

Cholesterol also can be synthesized in the cell from acetyl CoA formed in the mitochondria. A rate-limiting step in the synthesis of cholesterol is the conversion of 3-hydroxy-3-methylglutaryl CoA to mevalonate by the enzyme HMG CoA reductase. This enzyme is stimulated by LH in theca cells of the ovarian follicle and the corpus luteum.