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PERSPECTIVES IN BIOLOGY AND MEDICINE Volume 13 · Number 1 · Autumn 1969 THE BIOCHEMICAL FUNCTION OF B VITAMINS FRITZ UPMANN* Doctors like to prescribe vitamins and millions ofpeople take them, but it requires a good deal of biochemical sophistication to understand why they are needed and how the organism uses them. At the turn of the century, it was clearly recognized that a number ofdiseases were caused by nutritional deficiencies, and accessory food factors were found to be responsible . They had to be present in very small amounts and were named vitamins. They turned out to be strange chemical creatures with unexpected metabolic functions, in the exploration ofwhich I became strongly involved. Since they were needed only in small quantities, they were obviously not food in the ordinary sense. The diseases caused by lack of a vitamin were endemic in certain regions, and at first were often considered infectious, until it was discovered that they were due to a mysterious peculiarity of the food eaten in that particular region. As an example, I shall expand on beriberi, a destructive disease which was rampant in the Philippines andJapan, countries that subsistlargely on a rice diet. Since beriberi occurred almost exclusively in regions where the ricewaspolished, itwas suspected thatremoval ofthe germ and outerlayer from the brown rice might be responsible. Eijkman [1] was the first to show that beriberi could be cured by adding rice shavings to the diet. Casimir Funk imaginatively recognized the importance ofthese food accessories , and was among the first to purify the beriberi-curing substance from rice shavings and yeast. He characterized it as a nitrogenous base and therefore called it Vitamin [2], the name that has remained with us, even though not all vitamins are nitrogenous bases. * The Rockefeller University, New York 10021. Publication costs were kindly contributed to Perspectives by Miles Laboratories, Inc. After the beriberi-curing vitamin was chemically identified, it was renamed thiamine, meaning the sulfur-containin,g vitamin. However, it is still frequently called vitamin B1 since it was the first of the watersoluble B vitamins to be characterized. The letter A had been assigned to a fat-soluble vitamin that cures night blindness. Vitamin B1 is also called the antineuritic vitamin because the deficiency symptoms are predominantly neurological. The numbering of the B group has continued; the latest is B12, the cobalt-containing vitamin which cures pernicious anemia. B Vitamins as Part ofCoenzymes The curative amounts of the B vitamins were much too small to have any possiblenutritive value. Thus there arose the puzzling question: What good are they, and why do higher organisms or many strains ofmicroorganisms need these tiny food complements? After they were chemically identified, their structure often showed a complexity not found in other foodstuffs. Then, in the middle thirties, efforts were begun by Otto Warburg to characterize chemically compounds known as coenzymes, which are heat-stable cofactors in enzymatic reactions. Two coenzymes active in the oxidation or glucose 6-phosphate in red blood cells were the first to be chemically characterized in the Warburg laboratory. This oxidation required synergism of two enzymes, a glucose 6-phosphate dehydrogenase and a yellow-colored enzyme which reacted with oxygen. Both enzymes contained heat-stable coenzymes; the one in the dehydrogenase was easily removed from the protein. However, the colored substance in the yellow enzyme required treatment with strongly acid ammonium sulfate in order to be separated [3]. The greenish yellow fluorescent dye turned out to be the monophosphate ofriboflavin (first known as lactoflavin), which is a growth factor for rats. It was isolated from egg white shortly after its discovery in a coenzyme [4]. In 1935, the heat-stable factor in the dehydrogenase was identified by Warburg, Christian, and Griese [5] as a nicotinic acid derivative, a rather complex structure which Warburg named triphosphopyridine nucleotide (TPN). Its close relative, diphosphopyridine nucleotide (DPN), a heat-stable cofactor in cell-freealcoholic fermentation (fig. 1), was isolated in thesame laboratory and identified with cozymase, the first coenzyme, discovered by Arthur Harden [6] in 1909. The medical importance of nicotinic acid was not realized until two Fritz Lipmatm · Biochemical Function ofB Vitamins Perspectives in Biology and Medicine · Autumn 1969 years after Warburg's discovery of...

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Additional Information

ISSN
1529-8795
Print ISSN
0031-5982
Pages
pp. 1-9
Launched on MUSE
2015-01-07
Open Access
No
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