224 THE BIOCHEMISTRY OF B VITAMINS 



the activated acetate is believed to undergo first a condensation with 

 oxalacetic acid to form as-aconitic acid; then, by a series of dehydro- 

 genations, hydrations and dehydrations, and decarboxylations the cis- 

 aconitic acid is degraded to oxalacetic acid, which can then react with 

 another activated acetate and "carry" it through the same cycle.* 



Pantothenic acid is necessary for the initial condensation of the acti- 

 vated acetate (p. 195) ; thiamine is required for one step in the cycle, the 

 oxidative decarboxylation of a-ketoglutaric acid; nicotinic acid is neces- 

 sary for the dehydrogenation of the hydroxy acids, isocitric and malic; 

 a riboflavin enzyme may be the hydrogen acceptor in the conversion of 

 succinic acid to fumaric acid (p. 151). It is interesting to note that thia- 

 mine, riboflavin, nicotinic acid, and pantothenic acid are the vitamins 

 required for both the aerobic oxidation of carbohydrates and for the 

 anaerobic processes in which the carbohydrates are converted to fats. 



There are a number of compounds of general biological occurrence 

 and importance which are related chemically to the carbohydrates and 

 which are undoubtedly produced from them. These include the pentoses, 

 desoxypentoses, amino sugars, ascorbic acid, inositol, and the hexonic 

 and hexuronic acids. Nicotinic acid-containing coenzymes have been 

 shown to catalyze the dehydrogenation of glucose 13 or its phosphate 

 ester 14 to the corresponding acid, but the involvement of vitamin-con- 

 taining coenzymes in the biosynthesis of other sugar derivatives has not 

 yet been established. 



The mechanism by which the pentoses and desoxypentoses are generally 

 formed has not yet been definitely established. This subject is under 

 active investigation due to the present interest in nucleic acid metabolism. 

 When the mechanisms for the formation of these compounds, as well as 

 the other carbohydrate-like substances, are worked out, the vitamin 

 requirements will probably be obvious; or, conversely, if certain vitamins 

 are shown to be directly involved in the biosynthesis of any of these 

 substances, it will give some insight into the mechanisms and the inter- 

 mediates in their biosyntheses. If, for example, pantothenic acid were 

 shown to be essential for the synthesis of desoxyribose, a reasonable 



* In the past, on the basis of certain tracer experiments, citric acid has been 

 assigned the role of a metabolic by-product of the tricarboxylic acid cycle rather 

 than that of a necessary intermediate. In a more critical analysis of these tracer 

 studies it was pointed out that such an interpretation need not be made, and 

 subsequent to the preparation of this diagram it was shown experimentally that 

 citrate, rather than cts-aconitate, is the initial compound formed by the condensation 

 of the reactive acetyl unit with oxalacetate. (See Stern, J. R., and Ochoa, S., J. Biol. 

 Chem., 179, 491 (1949) and Potter, V. R., and Heidelberger, C, Nature, 164, 180 

 (1949)). 



