THE BIOLOGY BOOK

Cholesterol Metabolism

Adolf Windaus (1876–1959), Feodor Lynen (1911–1979), Konrad Emil Block (1912–2000), Robert B. Woodward (1917–1979), Joseph L. Goldstein (b. 1940), Michael S. Brown (b. 1941)

1974

When cholesterol comes to mind, it is reflexly associated with atherosclerosis, heart attack, and stroke. However, this solid steroid alcohol is essential for building and maintaining animal cell membranes as well as their permeability and fluidity, which allows proteins and other compounds to move within the membrane’s two layers. It is the starting molecule for the biosynthesis of such steroid compounds as bile, which plays a role in the digestion and absorption of fats, and for the synthesis of vitamins A, D, E, and K, the adrenal gland hormones cortisol and aldosterone, and the male and female sex hormones. Cholesterol is also a key component in the myelin sheath that surrounds and insulates the axon, which facilitates conduction of nerve impulses.

Cholesterol was first found in the bile and gallstones in 1769 and in the blood in 1833. Later research focused on its chemistry and metabolism, and the health risks associated with elevated levels. In 1903, Adolf Windaus determined its chemical structure. In 1951, the preeminent organic chemist Robert Woodward synthesized it.

During the 1950s, Konrad Emil Block and Feodor Lynen, working independently, determined the biosynthesis of cholesterol. Block traced its synthesis from a 2-carbon acetate to the 27-carbon, four-ring structure of cholesterol, involving twenty-six enzymes. Biosynthesis of cholesterol is regulated by the existing body levels of cholesterol via a negative feedback system; a higher dietary intake leads to decreased biosynthesis and vice versa. In 1974, Michael S. Brown and Joseph L. Goldstein at the University of Texas Southwestern Medical School identified a series of molecules that regulate cholesterol metabolism. Statins, inhibitors of cholesterol synthesis at its rate-limiting step (slowest step in reaction), are among the world’s most widely used drugs.

To date, thirteen Nobel Prizes have been awarded to researchers who have studied cholesterol, and it has been said, perhaps without hyperbole, that it is “the most highly decorated small molecule in history.” These Nobel laureates include Windaus (1928), Woodward (1951), Block and Lynen (1964), and Brown and Goldstein (1976).

SEE ALSO: Metabolism (1614), Negative Feedback (1885), Progesterone (1929), Stress (1936).

Blocked arteries caused by a buildup of cholesterol—a disease called atherosclerosis—are a major cause of death in Western countries. As the blood flow becomes blocked, blood clots develop within the artery. When the clots break off, they can block blood flow to the arteries in the heart and brain, resulting in a heart attack and stroke, respectively.