COENZYMES DERIVED FROM B VITAMINS 167 



Reactions of a-Ketoglutarate Catalyzed by Thiamine Pyrophosphate. 



ot-Ketoglutaric acid has been shown to be enzymatically decarboxylated 

 by three different mechanisms. 



(1) Simple decarboxylation 160 



O o o 



HO— C— CH 2 — CH«— C— C— OH — >■ HO— C— CH 2 — CH 2 — CH + C0 2 

 a-ketoglutaric acid succinylsemialdehyde 



(2) Aerobic oxidation requiring phosphate 151 



O 



HO— C— CH 2 — CH 2 — C— C— OH + H 3 P0 4 — > 

 a-ketoglutaric acid 



O O 



II II o 



HO— C— CH 2 -CH 2 — C— 0-P— OH + C0 2 + [2H] (/7apo - pro ^ n?) 



OH 

 succinyl phosphate 



(3) Aerobic oxidation independent of phosphate 150 







HO— C— CH 2 — CH 2 — C— C— OH + V 2 2 — > HO— C— CH 2 — CH 2 — C— OH + C O 

 a-ketoglutaric acid succinic acid 



Each of these reactions resembles a comparable one in which pyruvic 

 acid is the substrate; hence they need not be discussed in detail. The 

 apoenzymes for the two substrates have similar physical properties, but 

 they are not identical and cannot substitute for one another. The same 

 ions (Mg ++ or Mn ++ ) are required as cofactors. No demonstration has 

 been made of the existence of a phosphorylated succinyl compound 

 analogous to the phosphoryl-acetyl intermediate; hence succinyl phos- 

 phate is shown as the initial product of the phosphorylative oxidation. 



A phosphoroclastic cleavage, forming succinyl phosphate and formic 

 acid, has never been shown to occur in any organism. However, in 

 muscles perfused with pyruvic acid considerable amounts of succinic 

 and formic acids accumulate (p. 197). This suggests that there may be 

 enzymes present to handle the a-ketoglutaric acid (formed from pyruvic 

 acid) by such an anaerobic cleavage if the oxidative decarboxylation 

 system is overtaxed or not functioning. 



Relationship of the Structure of Thiamine to its Function. Attempts 

 have naturally been made to correlate the structure of thiamine with the 

 mechanism by which its coenzyme functions. The initial formation of a 



