136 Essays in Biochemistry- 



explain most of the phenomena that have been observed. Chaikoff 

 and Brown 16 as well as Green 10 have written extensive reviews of this 

 subject. 



With the, by now, conclusive evidence that acetyl CoA represents 

 the major if not the sole product of this oxidative cycle, the physiolog- 

 ical disposition of this central intermediate becomes of profound sig- 

 nificance. It has already been pointed out that it may condense with 

 oxalacetate to form citrate presumably for oxidation to C0 2 by way 



Fat 



w 



/RCO-CoA 



/ ~,, Ac -CoA 

 Glucose v ' 



/ 



II 



Fragments i ' Deacylase 



ueacyiase 

 I CH 3 COCH 2 CO - CoA »► CH 3 COCH 2 COO " 



\ 1 \ 



CH3COCOOH ^ CH 3 CO -CoA L_^ CH 2 CO -CoA 



I 

 I 

 I 

 I +co 2 



COCOOH 



I + 



' •- CH.,COOH 



Acetylations 

 Citrate 



CH3-C-OH 



CH 2 COO" 



\ 



Cholesterol 



I 



C0 2 + H 2 



Fig. 2. Metabolic pathways of acetyl CoA. 



of the tricarboxylic acid cycle. Its self-condensation to form aceto- 

 acetate has also been mentioned. In addition to its function as an 

 acetylating agent, it may also be utilized for the biosynthesis of fatty 

 acids and cholesterol. 



It has, of course, been known for a long time that labeled acetate 

 is incorporated into fat by rat-liver slices. Similar experiments have 

 more recently provided evidence that short-chain fatty acids are to 

 a considerable degree cleaved to "active acetate" prior to their in- 

 corporation. With homogenates and now aqueous extracts of rat 

 liver 17 it has been possible to demonstrate the incorporation of pyru- 

 vate or acetyl CoA into fatty acids. In view of the conclusive evidence 

 that pyruvate is converted in large measure to acetyl CoA by means 

 of pyruvic oxidase, it now becomes clear that glucose must be converted 

 to fat primarily by way of pyruvate and acetyl CoA. The first major 

 metabolic process in the transformation of carbohydrate to fat is 

 therefore glycolysis. This is probably true for most tissues; among 



