30 II. BIOSYNTHESIS 



c. The Chemical Nature of Coenzyme A. Lipmann and his colleagues ^"^ 

 first reported the presence of the component of the vitamin B complex, 

 pantothenic acid, in their partially purified preparation of CoA. In fact, 

 Kaplan and Lipmann^ ^ found that the pantothenic acid in the tissues be- 

 haved like CoA. In the investigation of the pantothenic acid content of a 

 partially purified CoA preparation, Hegsted and Lipmann^ ^^ showed that 

 a parallelism exists between pantothenic acid content and CoA activity. 

 It was later reported that the CoA concentration in the liver of ducks de- 

 creased quite rapidly to 40% of the normal activity when the fowl was 

 placed on a diet deficient in pantothenic acid. ^^'^ 



NovelU and co-workers"^ prepared pantothenic acid by treatment of 

 CoA with an intestinal phosphatase, followed by treatment with an ex- 

 tract of acetone-dried pigeon hver. This destroys the enzymic action of 

 CoA. In a later pubhcation of the Lipmann group, ^^ the presence of panto- 

 thenic acid in CoA was again confirmed. 



Adenyhc acid has likewise been identified as a component of the CoA 

 molecule.'*^ Another important group is the sulfur-containing amino 

 compound which is beheved to be mercaptoethylamine.^^-^^" Pantothenic 

 acid is linked to this sulfur-containing compound through the carboxyl 

 group of i3-alanine of pantothenic acid.^^-^^' Pantothenic acid is connected 

 with adenylic acid by a pyrophosphate bridge, ^-^ which probably involves 

 the 7-hydroxyl of pantothenic acid. ^23,124 ^ ^j^ij-d phosphate group occurs 

 on the ribose of the adenyhc acid as a monoester^-^ in position 2' or 3'. 

 The acetyl mercaptan group in acetyl-CoA was further identified by an 

 absorption maximum at 232^1, which is the absorption value previously re- 

 corded by Sjobergi^^ ^^^(^ ^y Stadtman;^" ^j^g latter author later followed 

 the acetylation of CoA spectrometrically by measuring the increase in 

 density at 240m due to the formation of the thioester hnkage.^^^ On the 



118 D. M. Hegsted and F. Lipmann, /. Biol. Chem., 174, 89-92 (1948). 

 1" R. E. Olson and N. O. Kaplan, /. Biol. Chem., 175, 515-529 (1949). 



118 G. D. NovelU, N. O. Kaplan, and F. Lipmann, /. Biol. Chem., 177, 97-107 (1949). 



119 W. H. DeVries, W. M. Govier, J. S. Evans, J. D. Gregory, G. D. Novelli, M. Soodak, 

 and F. Lipmann, /. Am. Chem. Soc, 72, 4838 (1950). 



120 E. E. SneU, G. M. Brown, V. J. Peters, J. A. Craig, E. L. Wittle, J. A. Moore, V. M. 

 McGlohon, and O. D. Bird, /. Am. Chem. Soc., 72, 5349-5350 (1950). 



121 G. M. Brown, J. A. Craig, and E. E. SneU, Arch. Biochem., 27, 473-475 (1950). 

 i"G. D. NovelU, N. O. Kaplan, and F. Lipmann, Federation Proc, 9, 209 (1950). 

 1" J. Baddiley and E. M. Thain, Chemistry & Industnj, 1951, No. 17, 337-338. 



12^ J. Baddiley and E. M. Thain, /. Chem. Soc, 1951, 2253-2258. 



126 J. Baddiley and E. M. Thain, /. Chem. Soc, 1951, 3421-3424. 

 i2« B. Sjoberg, Z. physik. Chem., B 52, 209-221 (1942). 



127 E. R. Stadtman, /. Biol. Chem., 203, 501-512 (1953). 



128 E. R. Stadtman, /. Cellular Comp. Physiol, 4I, suppl. 1, 89-107 (1953). 



