chemical vignette/ A Pac-Man for Cholesterol Since the 1960's we've known that high levels of cholesterol correlate with heart ailments. the maior cause of death in the United States. What we need is a Pic- an to chomp up the cholesterol in the blood and reduce "hardening" of the arteries that carry hlood from the heart (atherosclerosis). Now a lowly fungus-not unlike the famous mold, penicillium-may have shown us one. A normally functioning human cell uses a dual system for meeting its cholesterol needs. First, the cell has i t own factory to manufacture cholesterol. In addition, the cell's exterior has a number of lipoprotein receptors that can grab onto cholesterol-containing lipoproteins as they pass by in the bloodstream and null them inside. The cell fixes the number of these Pac-M&-like receptors so that just the right amount of i m ~ o r t e dcholesterol is added to the factorv-made product. 1f thk inner cell cholesteral level falls too low, more receptors are added to extract more from the hlood stream. here's an idea! If the cell's cholesterol factory could he slowed down, would the cell produce more receptors to make up the difference from the hlood stream supply? A chance to test this scenario came when a biochemist discovered that certain fungi produced something that inhibited cholesterol synthesis. Chemists joined in the plot, purified the effective com~ound.determined its structure. and named i t COM- - - PACTIN. this structure, chemists were able to svnthesize close relatives of comnactin that are even more potent. Chemical tests with these new chemicals indicate that the scheme works as planned. The inhibitor slows down
nowin in^
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the cellular cholesterol factory, the cell produces more lipoprotein receptors, and the hlood cholesterol level drops. The importance of this is shown by the fact that the average person with double the normal hlood level of cholesterol can expect to live only 45 to 50 years. For the few unlucky people with triple the normal amount, life expectancy drops to 30 or 35 years. T o complicate matters, 1in 500 Americans has the genetic disease familla1 hypercholesterolemio (FH). Victims of FH don't produce enough receptors a t their cell surfaces, so lipoproteins accumulate in the blood and eventnaly cause heart attacks. Thus clinical researchers are excited to find that the new cholesterol-inhibitors work with FH patients, bringing the hlood levels of cholesterol all the way down to the normal level. Much research remains, but these moldy chemicals offer immediate hope to FH sufferers and, in the future, to all people with abnormally high blood cholesterol. These short vignenes are taken from "Opportunities in Chemistry". copyright 1985 by the National Academy of Sciences and reprcduced with its permission. This compehensive report on future direetions and goals for chemical research contains much information bath on chemistry and manpower and education that is of use to the teacher; these visnenes are beino because of lheir obvi- reDroduced . ous wide utility in the classroom. The full report can be purchased far $28.50 ciothbaund and 518.50 paperbound from: National Academy Press, 2101 Constitutian Avenue. NW. Washington. DC 20418 A quantitydiscountof 15% far 5-24 copies and 25% f a 25-499 copies is availbe; all orders must be prepaid.
Volume 63
Number 11 November 1986
969
