312 F. LYNEN, S. OCHOA VOL. 12 (1953) 



protein can be precipitated from these solutions with ammonium sulfate at pK 3.6 as 

 in the method of Warburg and Christian'^ for the resolution of the flavoprotein D- 

 amino acid oxidase. The activity of the protein can be restored by the addition of 

 flavin adenine dinucleotide which has been found to be the prosthetic group of the 

 enzyme. Thus, like fumarate reductase, ethylene reductase appears to be a flavoprotein. 

 DPNH or TPNH cannot substitute for the leucodye. 



In line with the above observations Green and co-workers^*'* have recently reported 

 on the isolation of flavoproteins from ox liver catalyzing the oxidation of butyryl-S-CoA 

 and some higher acyl-S-CoA derivatives in the presence of triphenyltetrazolium as 

 hydrogen acceptor. The prosthetic group appears also to be FAD. 



There is thus little doubt that the enzymes of the ethylene reductase class are 

 flavoproteins. The nature of the electron transport system in the cell mediating the 

 transfer of hydrogen from the reduced flavoprotein to molecular oxygen is still unknown. 

 During fatty acid synthesis, hydrogens made available through oxidation of carbo- 

 hydrate as reduced pyridine nucleotides must be transferred to the ethylene reductase 

 flavoproteins to effect the reduction of the a,/3-unsaturated S-acyl-CoA fatty acid 

 derivatives. How such interaction takes place is also unknown. 



SUMMARY 



The intermediates in the biological breakdown and synthesis of fatty acids are S-acyl derivatives 

 of coenzyme A. 



Fatty acid synthesis is accomplished through repetition of a cycle of four consecutive reactions: 



a. Condensation of two molecules of acetyl CoA to form acetoacetyl CoA and coenzyme A (CoA-SH) ; 



b. reduction of acetoacetyl CoA to /3-hydroxybutyryl CoA; c. dehydration of /?-hydroxybutyryl CoA 

 to crotonyl CoA, and d. reduction of crotonyl CoA to butyryl CoA. A new cycle is started by the 

 reaction of butyryl CoA with another molecule of acetyl CoA, to form ^-keto-caproyl CoA -f CoA-SH, 

 and so forth. The cycle is repeated eight times until stearyl CoA is formed. 



All four reactions of the fatty acid cycle are reversible and fatty acid oxidation, once the fatty 

 acid is activated through conversion to the corresponding S-acyl CoA derivative, proceeds by a 

 reversal of the above sequence. 



There are two main mechanisms for activation of fatty acids: (a) By a reaction with ATP and 

 CoA to form S-acyl CoA, adenosine monophosphate and pyrophosphate, and (b) by transfer of CoA 

 from certain acyl CoA compounds such as acetyl CoA or succinyl CoA. 



The isolation and identification of some of the key enzymes of fatty acid metabolism is outlined 

 and their mechanism of action discussed. 



RfiSUMfi 



Les intermediaires dans la degradation et la synthese biologique des acides gras sont des derives 

 S-acyles du coenzyme A. 



La .synthese des acides gras est le resultat de la repetition d'un cycle de 4 reactions cons^cutives : 

 (a) condensation de deux molecules d 'acetyl CoA conduisant a I'acetoacetyl Co.\ et au coenzyme .A 

 (CoA-SH), (b) reduction de I'acetoacetyl CoA en ^-hydroxybutyryl CoA, (c) deshydratation du 

 /3-hydroxybutyryl CoA en crotonyl CoA, et (d) reduction du crotonyl CoA en butyryl CoA. Un 

 nouveau cycle recommence par la reaction du butyryl Co.\ avec une autre molecule d'acetyl Co.\, 

 qui donne le /9-cetocaproyl CoA + CoA-SH, et ainsi de suite. Le cycle sc repete huit fois jusqu'a 

 la formation du stearyl CoA. 



Les quatre reactions du cycle des acides gras sont reversibles et I'oxydation d'un acide gras, 

 apres son activation par transformation en derive S-acyle du Co.\, suit le chemin inverse de la 

 synthese. 



II y a deux m^canismes principaux d'activation des acides gras: (a) par une reaction avec ATP 

 et Co.\ qui donne du S-acyl CoA, dc I'adenosine monophosphate et du pyrophosphate et (b) par 

 transfert du CoA de certains acyl Co.\, tcls que I'acctyl Co.A et le succinyl Co.V. 



L'isolement et I'identification de quelques-uns des enzymes essentiels au metabolismc des acides 

 gras sont esquisses et leur mecanisme d'action discute. 



References p. 313J314. 



