LIPIDE METABOLISM 455 



enzymes responsible lor the various steps in the oxidation process have 

 been isolated from liver mitochondria. 



Recent investigations show that fatty acids must be activated before 

 they are oxidized. Such activation involves the transformation of the 

 free fatty acids to the corresponding acyl CoA derivatives. It is be- 

 lieved that the bulk of fatty acid activation takes place in various 

 organs such as liver, heart, and kidney and is catalyzed by the thio- 

 kinases in the presence of ATP: 



tliiokinase 



RCOOH + HS • CoA + ATP , 



RCO • S • CoA + AMP + HP2O7" 



The ac)l derivatives are joined to the CoA through the thiol group 

 of the latter pyrophosphate. 



After activation, fatty acids are oxidized in four steps involving 

 reversible dehydrogenation, hydration, oxidation to ketone, and finally 

 cleavage to yield the next shorter acyl CoA and acetyl CoA. A sche- 

 matic summary of these reactions is shown below: 



RCH2CH2COSC0A + FAD dehydrogenase " RCH = CHCOSCoA + FADH2 



DPN"^ 



+ H2O 



enoyl 

 hydrase 



X |3-hydroxyacyl 

 RCCHoCOSCoA + DPNH + H ^======^ RCHCH2COSC0A 



■^ dehydrogenase I 



o 



' 



OH 



thiolase 



RCOSCoA + CH3COSC0A 



The metabolic importance and fate of acetyl CoA are discussed in 

 Chapters 7, 9, and 20. 



As shown above, the oxidation of a fatty acid containing an even 

 ninnber of carbons results in final degradation to acetyl Coy\. On the 

 other hand, the final oxidation residue of a fatty acid containing an 

 odd number of carbons is jMopionyl CoA. The major pathway of 

 propionyl CoA in the animal involves the conversion of this active 

 fragment first to methylmalonyl CoA through the fixation of carbon 

 dioxide and finally the isomerization of methylmalonyl CoA (isosuc- 

 cinyl CoA) to succinyl CoA by an isomerase which does not seem to 

 require any cof actors. These reactions may be summarized as follows; 



