580 



NEW AND UNIDENTIFIED GROWTH FACTORS 



2. When ferricyanide replaces oxygen as the final electron acceptor, CoA 

 and DPN may be by-passed, although the requirement for DPT and lipoic 

 acid remains. 



3. When no oxidation occurs, as in acyloin formation, CoA, DPN, and 

 lipoic acid may all be omitted; however, DPT is still required. 



From these observations it appears that in these organisms LTPP may 

 be involved in dehydrogenation at a very early stage in the breakdown of 

 pyruvate. This is in line with the report by Sanadi et al.^'' that pig heart a- 

 ketoglutaric oxidase contains up to 6 moles of lipoic acid and about 1 mole 

 of cocarboxylase per mole of enzyme, but no DPN or CoA. Schemes sug- 

 gesting possible sequences of reactions have been proposed, ^^' ^^''^^ which 

 may be summarized approximately as follows : 



CH3COCOO- 



DPT 



^4( 



o 



CH3— C:J DPT+ -t- CO2 

 (acetaldehyde — DPT complex) 



(1) 



This complex may then be oxidized by hpoic acid, presumably in the 

 disulfide form. Whether this step involves the lipoic moiety for the first 

 time, or whether LTPP is the actual acceptor in reaction 1, is speculative. 

 In either case the cyclic disulfide may react to produce an acyl lipoate: 



O 



II 

 [CH3-C:]- 



H2 

 I CH2 



S-C-CHR 



O 



CH3-C~S-CH2 ^^^ 



s- 



(2) 



CH3-C~S-CH 



OH- 



H2 



CoA-SH II /^\ 



* CH3-C~S-CoA + H2C ^CHR 



I I 



SH S- 



(3) 



UPN^ 



H, 



H.C^ XHR 



I + DPNH 



(7) 



According to this scheme, the acetyl CoA produced in reaction 3 is removed 



" D. R. Sanadi, J. W. Littlefield, and R. M. Bock, ./. Biol. Chem. 197, 851 (1952). 



38 M. Calvin and P. Massini, Experientia 8, 445 (1952). 



39 M. Calvin, Chem. Eng. News 31, 1735 (1953). 



^° L. J. Reed, Symposium on Metabolic Significance of Vitamins, American Insti- 

 tute of Nutrition, Federation Proc. 12, 558 (1953). 



