MULTIPLE ENZYME SYSTEMS 



malonic acid derivatives to test in this system based on the knowl- 

 edge that purines could be synthesized this way chemically (26) 

 and guessing that the ribose residue was introduced later. 

 Buchanan and his co-workers (1) made similar excursions. 



But synthesis of intermediates can be fruitful. Thus the 

 use of tetrahydrofolate as a one-carbon acceptor was based on 

 the observation that citrovorum factor (N^-formyltetrahydro- 

 folate) after activation with ATP transferred a one-carbon unit 

 to a purine precursor (13). On the basis of balance studies 

 5-phosphoribosylamine was synthesized and found to enter into 

 purine nucleotide biosynthesis. On the basis of a number of 

 objective findings Shemin and Russell (27) synthesized amino- 

 levulinic acid and showed it to be an effective precursor of the 

 pyrrole rings and to be synthesized in vitro. 



MODEL SYSTEMS 



The organic chemist traditionally studies a complicated 

 mechanism with some model reaction or compound with which 

 he is familiar. This procedure has become increasingly important 

 to the biochemist and is especially useful in the study of multi- 

 enzyme systems. It may allow him to get at the nature of an 

 intermediate when other approaches have proved more difficult. 

 Acetate is not, per se, an intermediate in metabolism. How- 

 ever, there can be no doubt that the study of the activation of 

 acetate by Lipmann and by Lynen and their co-workers (20, 

 21) represented a powerful wedge into the problem of pyruvate 

 and fatty acid oxidation. By using .S'-acyl drivatives of A^- 

 acetyl thioethanolamine as model substrates Lynen (21) was able 

 to conduct a brilliant series of studies on the mechanism of fatty 

 acid synthesis and degradation. Since coenzyme A, the neces- 

 sary acyl acceptor, was not readily available, he used this model 

 to purify the individual enzyme steps. Williams and Buchanan 

 (30) studied the reaction of hypoxanthine with a ribose derivative 

 to form inosinate to gain information on the nature of the ribose 

 compound ultimately involved in the de novo synthesis of purine 

 ribotides. We have studied the activation of formate, which 



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