LIPIDE METABOLISM 459 



The carbon dioxide addition serves to activate the methylene group, 

 but carbon dioxide is lost again during the condensation reaction. 

 The net reaction, assuming R = CH^, is the same as the first mecha- 

 nism proposed: 



O 



2CH3C— S— CoA + ATP + TPNH + H3O+ ^ 



O 



11 

 CH3CH— CH.C— SCoA + TPN+ + HP0O7" + AMP + CoASH + H.O 



I 

 OH 



Clearly either pathway can repeat itself with the addition of more 

 acetyl CoA to the butyryl CoA or reduction product. Thus, by repeti- 

 tive steps, carbon chains can be increased 2 carbons at a time, pro- 

 ducing longer-chain fatty acids at each turn. In order for the lipogenic 

 process to operate, sources of DPNH and TPNH are needed. DPNH 

 is produced by many dehydrogenations, but the majority of TPNH 

 is formed during the dehydrogenation reactions of the isocitrate in 

 the Krebs cycle and the phosphogluconic acid oxidative (pentose- 

 phosphate) pathway (Chapter 9). 



In the normal animal, the intermediate free fatty acids of varying 

 chain lengths do not accumulate in significant amounts. Similarly, 

 fatty acid chains are not increased 2 carbons at a time over an in- 

 definite period of time. Rather it has been found that the reaction 

 sequences described above are terminated by a reaction first described 

 by Kornberg and Pricer. This reaction is specific for a-glycerophos- 



2RCOC0A + CH2OH > CH2OOGR 



Acyl CoA I I 



CHOH GHOOGR + 2CoA 



1 I 



CH2OPO3H2 CH2OPO3H2 



a-glycerophosphoric a-phosphatidic 



acid acid 



phate and takes place preferentially with 16- and 18-carbon acid 

 derivatives. On hydrolysis of the phosphatidic acid by phosphatase, 

 a diglyceride is formed which will in turn react with another mole of 

 acyl CoA to form a triglyceride. 



Fatty Acid Conversions 



As pointed out in previous sections, an animal obtains fatty acids 

 from the lipides included in the diet and from the biosynthesis of 



