b INTERMEDIARY METABOLISM AND GROWTH I 



Acetyl-CoA is a key intermediate of metabolism. The acetyl unit of the molecule 

 may either be converted to citrate (see section 5), or utilized for the synthesis of 

 fatty acids and sterols, or for the acetylation of certain amines or alcohols, such as 

 glucosamine or choline. 



-/. The fatty acid spiral 



Neutral fats are hydrolysed to fatty acids and glycerol prior to further catabolism. 

 The glycerol moiety of the molecule may be phosphorylated to a-glycerol phos- 

 phate, which can then undergo oxidation to dihydroxyacetone phosphate, a 

 glycolytic intermediate. 



The fatty acids are oxidized by way of the 'Tatty acid spiral" (Lynen, 1955). 

 Fatty acids must be activated to acyl-CoA-thioesters prior to oxidation. ATP is 

 required in the activation reaction which is catalyzed by thiokinase enzymes 



Fatty acids 



Phosphatides 

 -fats 



ATP 



CoA-SH 



-CH,-CHrCH,-CO-SCoA 



2H (FAD^^-FADHj) 



(Acyl -dehydrogenase) 



-CH-CO-S-CoA 



CH3-CO-SC0A 



(/3-Ketothiolase) 

 CoA-SH 



■CH2-CH = CH-CO-SCoA 

 H2O (Crotonase) 



CO-S-CoA 



Hydroxy -acyl -dehydrogenase) 

 + 2H (DPN+^-'DPNH+H*) 



-CH2-CO-CH2-COSC0A' 



Fig. 3. Fatty acid spiral. 



(Fig. 3). At least three kinds of thiokinases occur in liver (Kornberg and Pricer, 

 1953a; Mahler etal., 1953). The first is specific for tatty acids of chain length of 

 2, 3, or 4 carbon atoms, the second for fatty acids of intermediate chain length 

 (C4-CJ2), and the third for long chain fatty acids (Cj4-Cj8). 



The enzyme which activates fatty acids of chain length, C5-CJ2 is found 

 in the soluble portion of liver cytoplasm. Activity has also been demonstrated in 

 heart and kidney. On the other hand, the enzyme concerned with the activation 

 of higher fatty acids is found in the particulate portion of liver tissue. Mono-, di-, 

 or trienoic acids also serve as substrates for the latter thiokinase. 



The activated fatty acid is next oxidized by an acyl-dehydrogenase. Several 

 acyl-dehydrogenases have been noted. One of these, a copper containing flavo- 

 protein, oxidizes butyryl-CoA and fatty acid esters of CoA of chain length up to 

 eight carbons. Another, so called "Y," enzyme, contains iron as well as flavin and 

 oxidizes fatty acids of chain length C^-Q\^. A third iron containing flavoprotein, 

 the "Y2" enzyme, desaturates acyl esters of CoA of chain length of C14 or longer 



