54 CONTROL MECHANISMS IN CELLULAR PROCESSES 



and Magasanik, I960; Magasanik, 1960). By virtue of this kind of 

 inhibition, the antimetaboHte can slow the production of histidine 

 (which, in contrast to the antimetabohte, has repressor activity) and 

 hence can ]:)ring about derepression of the synthesis of enzymes in 

 the histidine pathwav. Yates and Pardee ( 1957 ) have obtained de- 

 repression in t]ie pyrimidine path of E. coli with 6-azauracil which, 

 presumably as nucleotide ( Handschumacher and Welcli, 1960), 

 acts as a false feedback inhibitor. 



A derepression effect in the tryptophan pathway in E. coli has 

 been demonstrated by Lester and Yanofsky ( 1960 ) through the use 

 of 3-methylanthranilic acid. This compound seems to function not 

 as an analogue of the end product, tryptophan, but rather as an 

 analogue of a tryptophan precursor. 3-Methylanthranilic acid can 

 curtail the synthesis of (the repressive) tryptophan, apparently by 

 inhibition of the conversion of anthranilic deoxyribulotide to in- 

 doleglycerol phosphate, and can thereby bring about derepressed 

 tryptophan synthetase formation. 



Although false feedback inhibitors, such as 2-thiazolealanine, are 

 not repressive, cases of "false repressor" action have been reported. 

 Thus, the guanine analogue 8-azaguanine strongly interferes with 

 the formation of inosinicase and of inosine 5'-phosphate dehydro- 

 genase, both of which are repressible by guanine. This interference 

 by 8-azaguanine is specific for these two enzymes and, under the 

 conditions used, does not extend to the formation of enzymes in 

 pathways other than those of purine synthesis ( Levin and Magasa- 

 nik, 1959; Magasanik, 1960). Recently, Tonomura and Novelli 

 (1960) showed that the repressive action of uracil on the production 

 of dihydroorotic acid dehydrogenase of £. coli can be mimicked, 

 with a measure of specificity, by cysteine, although the latter com- 

 pound does not seem to have an obvious structural similarity to 

 uracil; cysteine apparently can have the usual type of repressive 

 effect on enzymes of its own path of synthesis (Bourgeois et al., 

 1960). 



An instructive example of cooperative action of feedback inhibi- 

 tion and repression in the control of cellular function occurs in the 

 glyoxylate cycle of Micrococcus denitrificans. Kornberg et al. (1960) 

 have studied the change from autotrophy to heterotrophy (acetate 

 utilization) in this organism and found that this change is accom- 

 panied by a metabolic shift from the Calvin cycle to the glyoxylate 

 cycle; the operation of tlie latter cycle was concluded to be gov- 



