I. LII'OIC ACID 581 



as "acetate" via such reactions as 4, 5, or G. CoA-Sll is simultaneously re- 

 j>;eneralc(l lor use in I'eaction 3, whereas the oxidized functional form of 

 lipoate reappears in reaction 7 for use in reaction 2. Through the use of 

 flavoproteins and oxygen, or lactic dehydrogenase, DPX+ is made available 

 for re-use in reaction 7. When ferricyanide is the electron acceptor, an alde- 

 hyde-LTPP complex may be supposed to react according to efjuation 8: 



() 



II 

 CH,— C: 



+ 2Fe (CN)6 



LTPP 







T 



J + LTPP+ 



CH3— C J + LTPP+ + 2Fe (CN)6" (8) 



iOH- 

 CH3COOH 



Alternately, an aldehyde-DPT complex may combine with a second mole- 

 cule of aldehyde to produce acetoin. 



The foregoing reactions explain fairly well most of the observed require- 

 ments for lipoic acid, DPT, CoA, and DPX in the oxidation of pyruvate 

 (but not free acetaldehyde or ethanol^O by E. coli. and S. faecalis. However, 

 the need for LTPP when oxidation proceeds, in contrast to DPT when acy- 

 loins are formed, is not clearly explained. It is possible that the same apoen- 

 zyme might bind either co-factor. This has indeed been suggested,^" and an 

 experimental verification of this concept would permit a simpler presenta- 

 tion of reactions 1 and 2 above. 



These studies thus suggest that lipoic acid possesses at least three im- 

 portant functions in E. coli: first, as a primary (co)dehydrogenase in the 

 oxidation of a-keto acids; second, as an acyl transferase; and third, in the 

 transfer of energy through the formation of a "high-energj^" S-acyl bond, 

 which can be transferred to CoA and utilized in various biosynthetic reac- 

 tions. This full complement of activities may be restricted to certain orga- 

 nisms, however, since it has been reported^^, 4.3 ^|,^^ j,^ Telrahymena p3'ru^'ic 

 dehydrogenase activity was unaffected by the remo\'al of lipoic acid from 

 the system; only the acylation process was impaired by this treatment. It 

 would appear that lipoic acid is not the primary electron acceptor from 

 pyruvate in this organism. A role, as j^et undescribed, for lipoic acid in 

 animal systems is suggested bj^ its presence in a-ketoglutaric" and pyruvic 

 oxidases,''^ although dietary requirements for the factor have not been es- 

 tablished.^^ An active function in animal pyruvic dehj-'drogenase systems 

 is further hinted through the work of Peters et al.,*^ Stocken and Thomp- 



« H. D. Earner and D. J. O'Kane, J. Bacteriol. 64, 381 (1952). 



« G. R. Seaman, Proc. Soc. Exptl. Biol. Med. 80, 308 (1952). 



« G. R. Seaman, Proc. Soc. Exptl. Biol. Med. 82, 184 (1953). 



** D. E. Green, Science 115, 661 (1952). 



" E. L. R. Stok-stad, II. P. Broquist, and E. L. Patterson, Federation Proc. 12, 4-30 



(19.53). 

 " R. A. Peter.s, H. M. Sinclair, and R. H. S. Thompson, Biochem. J . 40, 516 (1946). 



