MCAT Biochemistry Review

Chapter 11: Lipid and Amino Acid Metabolism

11.4 Cholesterol Metabolism

Cholesterol is a ubiquitous component of all cells in the human body and plays a major role in the synthesis of cell membranes, steroid hormones, bile acids, and vitamin D.

SOURCES

Most cells derive their cholesterol from LDL or HDL, but some cholesterol may be synthesized de novoDe novo synthesis of cholesterol occurs in the liver and is driven by acetyl-CoA and ATP. The citrate shuttle carries mitochondrial acetyl-CoA into the cytoplasm, where synthesis occurs. NADPH (from the pentose phosphate pathway) supplies reducing equivalents. Synthesis of mevalonic acid in the smooth endoplasmic reticulum (SER) is the rate-limiting step in cholesterol biosynthesis and is catalyzed by 3-hydroxy-3-methylglutaryl (HMGCoA reductase. Cholesterol synthesis is regulated in several ways. First, increased levels of cholesterol can inhibit further synthesis by a feedback inhibition mechanism. Next, insulin promotes cholesterol synthesis. Control over de novo cholesterol synthesis is also dependent on regulation of HMG-CoA reductase gene expression in the cell.

SPECIFIC ENZYMES

Specialized enzymes involved in the transport of cholesterol include LCAT and CETP. Lecithin–cholesterol acyltransferase (LCAT) is an enzyme found in the bloodstream that is activated by HDL apoproteins. LCAT adds a fatty acid to cholesterol, which produces soluble cholesteryl esters such as those in HDL. HDL cholesteryl esters can be distributed to other lipoproteins like IDL, which becomes LDL by acquiring these cholesteryl esters. The cholesteryl ester transfer protein (CETP) facilitates this transfer process.

MCAT Concept Check 11.4:

Before you move on, assess your understanding of the material with these questions.

1.    Under what conditions is HMG-CoA reductase most active? In what cellular region does it exist?

2.    What proteins are specific to the transport and release of cholesterol, and what are their functions?