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Michael Brown and Joseph Goldstein: The Cholesterol Doctors
| Article
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15894 |
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Section : |
NATURAL SCIENCE
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| Issue
Date : |
1 / 1989 |
3,260 Words |
| Author
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Robert G. Fenley
Robert G. Fenley is a veteran science writer and former
director of medical information at the University of Texas
Southwestern Medial Center at Dallas. |
Atherosclerosis contributes heavily to cardiovascular disease, which accounts for about half of all deaths in the western industrialized world. In this disease, cholesterol accumulates in arterial walls, forming plaques that restrict blood flow, and the obstruction of an artery can eventually lead to heart attack or stroke: This much has been known for a long time. But it is the work of two Texas doctors--Michael S. Brown and Joseph L. Goldstein--that has delved into the how and why of life-threatening plaque formation.
Cholesterol has intrigued scientists ever since 1784, when it was extracted from gallstones. All cells incorporate cholesterol into surface membranes. The adrenal gland and ovaries convert cholesterol into the steroid hormones cortisol and estradiol. Another major use of cholesterol is the manufacture of bile acids, which are secreted into the upper intestine to emulsify dietary fats. But cholesterol's tendency to help clog arteries also makes it a deadly molecule.
By the 1960s, doctors knew a lot about cholesterol and its two-faced character, but no one knew exactly how the body regulated the substance--how the normal person managed to utilize an adequate amount without having too much in the bloodstream.
One type of cholesterol, low-density lipoprotein or LDL cholesterol, has especially been linked with plaque formation. In striving to understand the mechanisms that regulate the levels of LDL cholesterol in the bloodstream, Brown and Goldstein discovered the central role that an intriguing cellular mechanism called the LDL receptor has in removing LDL cholesterol from the body's circulatory system. Not only did their research open up new vistas of science, it laid the groundwork for understanding the broader problems of cardiovascular disease. It also afforded them the ultimate recognition of the 1985 Novel Prize in Medicine or Physiology.
The Receptor and FH
The central role of the LDL receptor in arteriosclerosis was first appreciated when Brown and Goldstein showed that its absence is responsible for a genetic disease called familial hypercholesterolemia, or FH. This is caused by mutations in a single gene responsible for creating LDL receptors.
There are two forms of this disease. FH heterozygous individuals have inherited a single mutant LDL receptor gene from their parents. These individuals have a
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