VITAMINS, ANTIBIOTICS, AND GROWTH 347 



folic acid is dehydrogenated to dihydrofolic acid in the process. The 

 hydrogen is restored by TPNH to regenerate the tetrahydropteridine 

 ring. From these brief examples we can see that folic acid is essential to 

 the formation of adenine, guanine, and thymine, three of the four bases 

 of DNA. Hence the relation of folic acid to growth is evident. 



The existence of a co-factor for acetylation, "coenzyme A," was 

 first noted in experiments with acetylcholine ( Nachmansohn, 1946). 

 This coenzyme, formed from the vitamin pantothenic acid and func- 

 tioning through the terminal sulfhydryl group of thioethanolamine, was 

 shown to transfer acetic acid and other carboxylic acids into larger 

 molecules by means of intermediate thioester compounds which con- 

 vey the necessary reactivity to the acyl groups. Acyl coenzyme A com- 

 pounds are the building units for many biological compounds, includ- 

 ing fatty acids, components of the tricarboxylic acid cycle, sterols, ster- 

 oids, terpenes, carotenoids, porphyrins, and a number of amino acids. 

 These syntheses underlie the essential nature of pantothenic acid for 

 growth. 



It was suggested in 1943 by Burk and Winzler that biotin acts as 

 a coenzyme for transfer of carbon dioxide and a relation between biotin 

 and carboxylation was repeatedly demonstrated in the ensuing years. 

 In 1959, Lynen and co-workers succeeded in preparing the active mole- 

 cule of COo-biotin and in showing that the carboxyl group replaced 

 hydrogen on one of the imino groups of the ring of the biotin molecule. 

 A carboxylation reaction of biotin is shown in Figure 10. It appears 

 that reactions of this type take place in the carboxylation of acetyl CoA, 

 propionyl CoA, and beta-methylcrotonyl CoA to form malonyl CoA, 

 methyl malonyl CoA, and beta-methylglutaconyl CoA, respectively. 



The participation of biotin in the interconversion of pyruvic and 

 oxalacetic acids, propionic and succinic acids, ketoglutaric and oxalo- 

 succinic acids is evidently due to the "biotin C02-biotin" transfer. The 



CH3 , -QOC-N^ ^NH 



I + I I ^ 



COSCoA HC -CH ^=^ 



HaCv^ ^CH(CH2) COOH 



CHp-COO" . HN^ ^NH 

 I +1 I 



COS CoA HC CH 



Figure 10. Transfer of carboxyl group by "Coo-biotin.' 



