Research progresses on how vitamins work Fast-paced discovery in nutritional chemistry has already translated into mass applications changing the food industry and consumer patterns. Further links in the still-hazy bio chemistry of vitamins and other nu trients, promising still more attention from regulators and users, came to light in many sessions at the annual meeting of the Federation of American Societies for Experimental Biology, in Atlantic City earlier this month. The wide variety of work on vitamin biochemistry presented at the meeting included reports on the effect of vitamin A on cholesterol in rats, on vitamin B12 transport in a bacteria cell system, and on the role of vitamin Ε and selenium in preventing a serious disease in chickens. The work on vitamin A as a de pressing agent on diet-induced highserum cholesterol in rats was carried out by John W. Erdman, Jr., and Dr. Paul A. Lachance at Rutgers University's department of food science. This work sought to distinguish whether specific vitamin A activity or a related carotenoid structure is responsible for lowering blood cholesterol. The general effect of vitamin A in lowering blood cholesterol in rats had emerged from several pre vious research projects. The Rutgers scientists examined serum, liver, and intestinal cholesterol concentrations of rats fed various levels of lycopene, a carotenoid without vita min A activity, in a 1% cholesterol diet deficient in vitamin A. Comparing the results to cholesterol levels in rats fed a control diet deficient in vitamin A, .the investigators found that all lycopene levels except one actually increased serum cholesterol concentrations in the rats. Similar results appeared in liver cholesterol levels, and no significant changes appeared in intestinal choles terol levels. In contrast, a diet strong in vitamin A, or precursor β-carotene, signifi cantly reduced serum cholesterol in rats on the 1% cholesterol diet. The Rutgers scientists conclude that they have further evidence that it is a vitamin A activity itself and not a related chemi cal structure that appears to stop the buildup of cholesterol in the serum and liver of rats fed a high-cholesterol diet. The Rutgers laboratory is now studying the mechanisms that may be involved in the cholesterol depression by vitamin A. The study presented at the FASEB meeting on vitamin B12 transport in a cell system of the bacteria, Escherichia coli, shows the vitamin competing with cell-destroying Ε colicins for the same receptor site on the cell's outer mem brane. This work was disclosed by Donna R. Di Masi, John C. White, and Dr. Clive Bradbeer of the University of Virginia's school of medicine. 18
C&EN April 30, 1973
Vitamin B12 is the only known nu trient, the scientists say, that enters the E. coli cells by using a binding pro tein tightly bound to the outer mem brane of the cell envelope. The 200 or so of these Bi 2 receptors per cell also appear to act as receptors for destructive protein antibiotics called Ε colicins, the data from this research show. As a result of the competition between the
antibiotics and the vitamin to occupy the receptor site, saturating concentra tions of B12 can protect the cells against these colicins. Hence, the receptor sites have the paradoxical functions of affording both the nutrition and the destruction of the cell. The scientists suggest, "The asso ciation of these disparate functions within a single structural element offers
Institute studies coenzyme Q and hormones Success in research these days requires competence in both science and management. So says Dr. Karl Folkers, Ashbel Smith Professor and director of the Institute for Bio medical Research at the University of Texas, Austin, and winner of the first International Robert A. Welch Award in Chemistry, a prize that includes $75,000. In conveying his views on re search to students, Dr. Folkers hopes to develop scientists, espe cially those who can do multidisciplinary work in a broad field of pioneering research in treatment of diseases. The research aims at finding treatments, when feasi ble, where none exists. The insti tute's efforts include many clinical studies, for as Dr. Folkers explains, the final exam comes when the stu dents learn if a treatment aids pa tients. Currently, Dr. Folkers directs the institute's work in just two fields —vitamin treatment of diseases and research on hypothalamic hor mones. He believes in a policy of concerted efforts rather than one with several diversified goals. In studying the use of a vitamin, coenzyme Q, for potential therapy in treatment of several diseases, Dr. Folkers' work includes clinical tests of dystrophic patients. Co enzyme Q was chemically elucidated before its use in medicine was se riously pursued, Dr. Folkers says. To bridge this gap, a group of sci entists at the institute designed coenzyme-Q-enzymology for human blood and other tissues which allows them to determine deficiencies of the vitamin in humans. Following several years' work with genetically dystrophic mice during which treatment using coenzyme Q was successful in prolonging the mice's lives, a strong shift to human disease was made. Early results of seven years' clinical studies were erratic, probably because patients tested had very advanced and irre versible muscular dystrophy. Many variables affected the tests. As a result, Dr. Folkers now in sists on treating boys in very early stages of the disease. Preclinical dystrophic boys and infants can appear rather normal, Dr. Folkers
says, but their blood shows highly abnormal biochemistry. The tests have had periods of con trols, treatment, and placebo. Since monitoring such therapy takes years, microtechniques are used to analyze a few drops of blood for the most critical enzyme, creatine phosphokinase. Two young boys, particularly, have benefited in clinical trials, Dr. Folkers says, with both showing a reduction of creatine phosphokinase, indicating that they have biochem ically benefited from coenzyme Q. Coenzyme Q work is now broad ened to cardiology, dentistry, and other disease areas. Ryo Nakamura, with doctorates in dentistry and biochemistry, joined the institute to work with Dr. Folkers on coen zyme Q in periodontal disease. Beginnings of this work came from recognition that coenzyme Q is in nearly all tissues of the body. Even the tissues surrounding teeth involve the biochemistry of coenzyme Q. The group has found deficiencies of coenzyme Q in the gingiva of some patients having periodontal disease. It seems reasonable that this disease can be a problem of both biochemistry and bacterial plaque, depending on the patient, Dr. Folkers says. It also seems clear, he says, that control of bacte rial plaque by good oral hygiene can not correct deficient biochemistry, and improved biochemistry will not cause the plaque to vanish. The other major area of work at the institute involves research on hypothalamic hormones. During the past three years, the chemical struc tures of two of these have been found through work at several lab oratories with some contributions from the institute. These hormones are little peptides, Dr. Folkers says, with incredible physiological potency and importance. One is the thyrotropin-releasing hormone and the other the luteinizing hormone-releasing hormone. They are expected to be especially useful in clinical diagnosis of the pituitary and in diseases in volving problems of fertility and reproduction. Use of these hypo thalamic hormones and new ones whose structures are yet unknown will usher in a new era of medicine, he adds.
