HENRY R. MAHLER 



designation of these enzymes. This brings us into the realms of 

 nomenclature, semantics, and philosophy and once again raises 

 the spectre of having to determine how and in what form enzymes 

 preexisted in the cell. For practical purposes the aim should be 

 to isolate these activities in a reproducible manner with constant 

 composition with respect to the characteristic chemical com- 

 ponents and tending toward homogeneity by physical, chemical, 

 and biological criteria. 



'&' 



Pyruvic and a-Ketoglutaric Dehydrogenases 



These were the first complex oxidative enzymes to be 

 isolated from animal tissues in a homogeneous form. The 

 reaction catalyzed by them, the nature of the prosthetic groups 

 and coenzymes involved, and other aspects of the catalytic 

 mechanism have been studied intensively (14,32) and will not 

 be covered here in extenso. The highly purified enzyme carries 

 out at least the following activities: (7) that of a carboxylase: 

 decarboxylation of the a-keto acid to a diphosphothiamin (or 

 diphosphothiamin-lipoic) -aldehyde complex, (2) oxidation to 

 an acetyl-lipoic complex (with the lipoic moiety reduced from 

 the disulfide to the ditliiol), {3) and {4) the reoxidation of 

 reduced lipoic acid by DPN, in conjunction with the transfer 

 of an acyl moiety from lipoic acid to CoA. Electron transport 

 from substrate to DPN is thus mediated by lipoic acid, and it is 

 at that level that alternate and bypath mechanisms might come 

 into play (e.g., the oxidation of pyruvate or a-ketoglutarate by 

 ferricyanide, dyes, or oxygen in the presence of the dehydro- 

 genase, but in the absence of either CoA or DPN) . 



Metallojiavoproteins 



A large group of flavoproteins has recently been shown to 

 contain metals in close association with their flavin prosthetic 

 groups and as an integral part of the electron transport mecha- 

 nism of these enzymes (29). Among the enzymes so classified 



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