423 Thiophenes, Imidazoles, Thiazoles, Isoxazoles 



By selective synthetic substitutions with blocking groups 

 at various positions in the two heterocycles, the active site 

 of the molecule has been located as the 2-position of the 

 thiazole ring.'^' '" It is here that pyruvic acid, for ex- 

 ample, is decarboxylated to form (still in combination 

 with thiamine pyrophosphate) "active acetaldehyde" and 

 a-ketoglutaric acid to form "active succinate." The active 

 acetaldehyde intermediate was shown in Section 2. It is 

 claimed that this intermediate has been isolated from 

 Escherichia coli.'^'^'' 



A thorough review of thiamine is available.^" 

 For more than 20 years biotin has been recognized as 

 a dietary requirement in higher animals and yeasts. It 

 was formerly called vitamin H, and animal deficiencies 

 could be induced by feeding raw egg-white. This contains 

 a protein, avidin, which complexes tightly enough with 

 biotin to cause avitaminosis. 



The biochemical function and mode of action of biotin 

 long remained obscure. It is now known to be a cocar- 

 boxylase or coenzyme component for the transfer of car- 

 bon dioxide. Some of the reactions which it catalyzes 

 are: 



CH3— C— COOH ^ HOOC— CHo— C— COOH is, 19, 20, 21 

 Pyruvic Acid Oxaloacetic Acid 



HOOC— CH— CHo— CH2—CH2—NH2 



I 

 NHo 



Ornithine 



HOOC— CH—CH2—CH2— CHo— NH—C—NH2 22, 23 



NH2 



Citrulline 



"Ronald Breslow, /. Am. Chem. Soc. 79 1762 (1957); 80 3719 

 (1958). 



^•^ Ronald Breslow and Edward McNeils, ibid. 81 3080 (1959). 



i«" Gerald L. Carlson and Gene M. Brown, /. Biol. Chem. 235 PC3 

 (1960). 



^' Paul D. Boyer, Henry Lardy and Karl Myrback (Eds.), "The 

 Enzymes" Academic Press, New York, 1960 Vol. II, David E. Metzler, 

 Thiamine coenzymes, pp. 295-337. 



^* Henry A. Lardy, Richard L. Potter and C. A. Elvehjem, J. Biol. 

 Chem. 169 541 (1947). 



