330 ANIMAL BIOCHEMISTRY 



OH 



I! II 



^ CH3 CHoCHaOPOPO^ 



3. ^- .i^n._^ 



CHo — Ni /S 



.0 



thiamine pyrophosphate (cocarboxylase) 



This cofactor is required in several enzymatic processes for the addi- 

 tion or removal of carboxyl groups. One of the principal reactions 

 known to require this coenzyme is the decarboxylation of pyruvate 

 with pyruvic dehydrogenase to form carbon dioxide and acetyl co- 

 enzyme A. This process is shown on page 171 as the connecting link 

 between glycolysis and the tricarboxylic acid cycle. Reactions catalyzed 

 by either transketolase or transaldolase also require thiamine py- 

 rophosphate. For example, see pages 213 and 216. 



The exact mechanism by which this coenzyme functions has not 

 been conclusively demonstrated. The most prevalent opinion holds 

 that it forms a complex with both the enzyme and the substrate. It is 

 known that the hydrogen attached to the carbon atom between the 

 nitrogen and the sulfur is very labile. As a result it has been sug- 

 gested that the carbonyl group of a-keto acids attacks this position and 

 imdergoes decarboxylation. The next step postulated involves transfer 

 of the acyl group to lipoic acid and finally, using the enzyme thiol 

 transacetylase, to coenzyme A. 



CH..CH.,CH(CH..)4COOH 



I 1 



SH SH 



lipoic (thioctif) iicid 



It is obvious that increased knowledge of metabolism is likely to 

 bring out additional roles played by thiamine or its derivatives. As a 

 matter of fact one special derivative has been reported in the bac- 

 terium Escherichia coli, where thiamine pyrophosphate was thought 

 to be coupled to lipoic acid. The resulting complex was then active in 

 the enzymatic decarboxylation of pyruvate. Other workers feel that 

 the thiamine pyrophosphate and lipoic acid are indeed both essential 

 but that the postulated amide bond between them does not exist. 

 Thus a complete mechanism of this key reaction is not available. 



Requirements 



All animals except the ruminants require a regular supply of thia- 

 mine in their diets. Ruminants need thiamine too, but the bacterial 

 flora of their rumens synthesize and liberate enough of the vitamin to 



