582 NEW AND UNIDENTIFIED GROWTH FACTORS 



soii,'''^ and Gunsalus.^^ The two former groups observed that the vesicant 

 arsenical Lewisite (CHC1=CH — ASCI2) was particularly effective against 

 the pyruvic oxidase system in pigeon brain, and that the attack was pri- 

 marily upon — SH groups in this system. Reversal of Lewisite oxide poison- 

 ing by BAL (2,3-dimercaptopropanol) was shared by other dithiols, but 

 not by monothiols. It was then shown^^ that Hpoic acid, hke BAL (but un- 

 like glutathione), was highly active in overcoming arsenate and arsenite 

 inhibition of apopyruvate dehydrogenase activity in S. faecalis. Whether 

 the lipoic acid functioned in the latter study as catalyst or substrate is not 

 clear; however, the high reversing power of lipoic acid is noteworthy (0.04 

 7 was somewhat less active than 100 7 of BAL). It is quite possible that 

 lipoic acid is one of the first compounds in the pyruvic oxidase system to be 

 inactivated by Lewisite.^^^ 



On the basis of the belief that lipoic acid possesses codehydrogenase func- 

 tions, Calvin and his associates'^ , 39 , 48 h^ye suggested the intriguing possi- 

 bility that this coenzyme may participate in the primary quantum con- 

 version act of photosynthesis. It was observed^^ that the incorporation of 

 C^'^Os into members of the citric acid cycle in green algae was strongly in- 

 hibited by light. This was at first interpreted as being due to the mainte- 

 nance (in light) of too low a concentration of a key intermediate required 

 for entry into the cycle, and, more recently, as a possible depletion of the 

 supply of oxidized lipoic acid available to oxidize pyruvate. The key reac- 

 tion is envisaged^^ as 



Chlorophyll (activated) + S -S — > Chlorophyll (ground state) -|- S S 



whereby lipoic acid is maintained as thijd-free radicals due to light-induced 



" L. A. Stocken and R. H. S. Thompson, Biochem. J. 40, 535 (1946). 



•"^ The postulated activity of lipoic acid in the dithiol form as an anti -arsenical 

 raises some questions as to the correctness of the proposed structures of LT and 

 LTPP,^^ if the latter are assumed to be the active forms of the comj^ound. Thus, 

 with a lipoic acid sulfur-protein link ruled out because of the low reversing power 

 of monothiols, only the pyrophosphate group remains for readj^ binding to the 

 apoenzyme. Such a linkage, however, would be expected to be weaker than that 

 known to exist between lipoic acid and protein.^- ^* Similar reservations apply to 

 the manner of attachment of LTPP to the apoenzyme during transport of the C2 

 unit to CoA. Other possibilities are: (a) rupture of the thiazole ring and attachment 

 to protein or thiamine through the S atom; (b) function of lipoic acid without thi- 

 amine in the arsenate reversing system; (c) an alternate structure of LT which 

 would i)ermit attachment through the carboxyl or amino groups. Further ex- 

 perimeiits are needed to determine the exact relationships of the various moieties 

 in lipoic acid systems. 



« M. Calvin and J. A. Barltrop, J. Am. Chem. Soc. 74, 6153 (1952). 



*^ A. A. Benson and M. Calvin, /. Expll. Bot. 1, 63 (1950). 



