III. BIOCHEMICAL SYSTEM 619 



COO- O 



C:0 ^ HCH2C + H2O 



\ 

 CH2 SCoA 



coo- 



i 



coo- 



HOC-CHoCOO- + HS-CoA + H+ 

 CH2 



COO- 

 Fig. 9. Citric acid synthesis from acetyl-CoA and oxalacetate. 



This reaction has now been fully clarified by the work of Lynen and his 

 group^'*", by parallel work in Green's laboratory"'' and by Stern and del 

 Campillo in Ochoa's laboratory."*^ The reaction is formulated as follows: 



CHs-CO-S-CoA + CH3-CO-S-CoA 



^ CHs-CO-CHo-CO-S-CoA + HS-CoA 



The equilibrium favors greatly the split of acetoacetyl-S-CoA + CoA-SH 

 to two moles of acetyl-S-CoA, the "thioclastic split" of Lynen."'^ In the 

 process of fatty acid synthesis the condensation is followed by DPN-linked 

 hydrogenation of acetoacetyl-CoA to /3-hydroxybutyryl-CoA. The /3-hy- 

 droxybutyryl-CoA, unlike the free Z-compound, belongs to the d-series."^ 

 It now is dehydrated to crotonyl-CoA, which then is hydrogenated by a 

 flavin enzyme to butyryl-CoA. The butyryl-CoA condenses further with a 

 new molecule of acetyl-CoA to the 6-carbon-j8-keto acyl-CoA and DPN- 

 linked hydration reduction; flavin-linked reduction and condensation con- 

 tinues until the 16- or 18-carbon chain is completed. Then stearyl or 

 palmityl-CoA condenses with glycerophosphate to form the phospholipids"-'' 

 and presumably with glycerol to yield neutral fat. 



'3° F. Lynen, Harvey Lectures, Ser. XLVIII, 210 (1954); F. Lynen, Federation Proc. 



12, 683 (1953). 

 "'^ H. Beinert, R. M. Bock, D. S. Goldman, D. E. Green, H. R. Mahler, S. Mil, P. G. 



Stansly, and S. J. Wakil, /. .4m. Chem. Soc. 75, 4111 (1953). 

 "<^ J. R. Stern and A. del Campillo, J. Am. Chem. Soc. 75, 2277 (1953). 

 ^3rf F. Lynen, Federation Proc. 12, 683 (1953). 



'3» A. L. Lehninger and G. D. Greville, ./. .4m. Chern. Soc. 75, 1515 (1953). 

 "/ A. Kornberg and W. E. Pricer, Jr., ./. Am. Chem. Soc. 74, 1617 (1952). 



