III. BIOCHEMICAL SYSTEM 625 



pathway of carbohydrate oxidation through citric acid synthesis and 

 through its function in ketogkitarate and pyruvate oxidation. Through its 

 function in citrate and ketoglutarate metaboHsm, furthermore, it is in- 

 volved in the synthesis of various amino acids, like glutamic acid,i°^ proline, 

 and others from carbohydrate sources. Through succinyl transfer, it seems 

 to enter into synthesis of the pyrrole ring in the heme molecule. Its role in 

 acetoacetate synthesis and its well established role in fatty acid and choles- 

 terol synthesis illustrate the instrumental part of the coenzyme in fat and 

 steroid synthesis. 



The unequivocal identification of acetyl-CoA with "active acetate" 

 makes it appear legitimate to presume that any incoiporation of isotopically 

 marked acetate indicates the intermediacy of acetyl-CoA at some stage of 

 the process. In this manner, by aiming at a closer recognition of the role 

 of acetyl-CoA, an opening is found for an enzymatic understanding of 

 such complex reactions as steroid, rubber, carotenoid, and terpene bio- 

 synthesis where acetate incorporation has been shown to occur. It is pre- 

 sumed that such structures are built up from 2-carbon residues exclusively, 

 as was shown to be the case for cholesterol by Bloch's investigations.^"' 

 James Bonner's work on the synthesis of latex in certain plants^"' indicates 

 that the isoprene unit may be derived from 2-carbon residues. 



It is, however, obvious that an incorporation of acetate into a biological 

 structure has to be viewed judiciously because, for example, by milling 

 through the citric acid cycle, acetate incorporates into a large number of 

 molecular species, as amino acid, carbohydrates, and others. These, in 

 their turn, represent building stones and will spread acetate secondarily 

 into many compounds. Although initially acetyl-CoA participates in a 

 derivation of such building stones, eventual synthetic mechanisms may 

 easily not involve this coenzyme. 



A few concluding remarks on the role of pantothenic acid in CoA appear 

 in order. Comparing CoA structurally to the pyridine and flavin adenine 

 dinucleotide, one finds that pantothenic acid, through its terminal hydroxyl 

 on the one side and the carboxyl on the other, links the reactive base cyste- 

 amine through the pyrophosphate bridge to the adenyl moiety, the latter 

 a common feature in many coenzymes. The question as to why in the case 

 of CoA this "tie" molecule has to have such an unusual structure remains 

 open, and the essentiality of the "precious" vitamin in this coenzyme still 

 presents a challenge to our biochemical imagination. 



1" S. Shive, W. W. Ackermann, and J. E. Sutherland, /. Am. Chem. Soc. 69, 2567 



(1947). 

 '"2 K. Bloch, Recent. Pro(jr. Hormone Research 6, 111 (1951). 

 "» J. Bonner and B. Arreguin, Arch. Biochem. 21, 109 (1949). 



