] 28 BIOCHEMICAL SYSTEMATICS 



Following this initial condensation, reduction occurs, and the 

 ketone group is eliminated. These reactions are accomplished in three 

 steps, two of which involve electron transfer from the pyridine 

 nucleotides (DPNH and TPNH). These steps are illustrated below. 



?" II 



(3) CHaCCHsC^S CoA p^'^" + "^ > CH3CHCH2CS CoA + DPN 



OHO O 



(4) CH3CHCS CoA — » CH3CH=CHCS CoA + H2O 



O O 



(5) CHaCH^CHCS CoA '^^''" ^ "^ > CH3CH2CH2CS CoA + TPN 



Degradation of fatty acids proceeds by the stepwise removal 

 of two-carbon units via a pathway which is essentially the reverse of 

 that described above. There are some differences however. For ex- 

 ample, the initial oxidative step, corresponding by analogy to step 

 5 above, in reverse, is mediated by the coenzyme flavine adenine 

 dinucleotide (FAD). A second point of difference is that it does not 

 appear that the temporary binding of CO2 to form the malonyl 

 derivative is involved. 



The significance of the mode of fatty acid synthesis described 

 above is that it represents an almost universal basic metabohc path- 

 way. Therefore, all of the various fatty acids are metabolically related, 

 and the variations in chain length, in degree of unsaturation, and even 

 those involving terminal cyclization, are secondary. 



A question of some theoretical importance is that of whether 

 a single enzyme of low specificity is involved in the condensation of 

 malonyl CoA with the preformed carbon chain or whether several 

 enzymes, each with affinities for a carbon of particular length, may 

 cooperate in the build up of a sixteen carbon fatty acid. In fact, it is 

 possible that a different, specific enzyme exists for coupling of 

 malonyl CoA to C2, C4, Ce . . . C„ residues. There is insufficient 

 evidence on this point, to the writers' knowledge, to provide a general 

 statement. Likewise, it is not yet known whether any specific coen- 

 zymes participate in the oxidation-reduction steps involving different 

 carbon chain lengths, or even whether similar coenzymes but different 

 apoenzymes participate. Crane et al. (1955) have shown that three 

 enzymes are active in the first oxidative step in the degradation of 

 fatty acids in pig hver, and their specificities differ for different car- 

 bon chain lengths. All three of these are fiavoproteins. As indicated in 

 Fig. 7-1, enzyme Yi is most active on C8-C12 fatty acids, Y2 on Cg- 



