454 ANIMAL BIOCHEMISTRY 



to the tissues. The liver also plays an important role in fat catabolism 

 when carbohydrate metabolism is subnormal. The catabolic reactions 

 taking place in the liver involve the hydrolysis of fats to glycerol and 

 fatty acids. Glycerol is converted to dihydroxyacetonephosphate (see 

 page 168) via formation of a-glycerophosphate and thus enters the 

 carbohydrate metabolic scheme. Fatty acids, on the other hand, are 

 degraded to several two-carbon units which either interact with 

 oxaloacetate and are converted to carbon dioxide (page 171) or react 

 with other two-carbon units to form acetoacetate which gives rise to 

 substances known as ketone bodies. These reactions are summarized 

 below. 



Fats ^=^ glycerol 



li 



glucose 



acetoacetate 



The degradation of fatty acids proceeds stepwise by a series of reac- 

 tions which removes two carbons at a time from the carboxyl end of 

 the carbon chain. This catabolic scheme is known as /3-oxidation. 



^-Oxidation 



In 1905, Knoop proposed a mechanism to explain the oxidation of 

 fatty acids in vivo. He conducted a series of experiments in which 

 oj-phenylaliphatic acids were fed to dogs, and the nature of the ex- 

 cretory products studied. He found that the aromatic nucleus resists 

 oxidation in the body while the side chain is shortened by an even 



number of carbons. For example, y8-phenylpropionic acid > benzoic 



acid, y-phenylbutyric acid > phenylacetic acid, while phenylacetic 



acid itself is not degraded further. Both benzoic acid and phenyl- 

 acetic acid are excreted in the urine in the form of their respective 

 glycine conjugates, hippuric acid (CgHr^CO-NH-CHoCOOH) and 

 phenylaceturic acid (CeHsCHoCONHCHoCOOH). 



On the basis of Knoop's conclusions and a wealth of experimental 

 evidence provided by many investigators since then, y8-oxidation has 

 become a firmly established metabolic pathway. Thus it is recognized 

 that fatty acid oxidation occurs as the result of a series of reactions 

 which effectively reduces the carbon chain two carbons at a time. The 



