This review has been limited to a consideration of those meta bolic inhibitors which exert their effects by virtue of their struc tural similarity to compounds playing a role in metabolism and growth. Previous reviews by Woolley, by Welch, and by Roblin (1 to 6) have shown the concept of competitive antagonism toward essential metabolites by compounds of similar structure to be so well established as to require little further justification.General considerations.-The high hopes held forth for the development of new chemotherapeutic agents based on a rational application of this principle [e.g. (7)] have not yet been realized. However, such metabolic antagonists have already begun to be of service in elucidating metabolic functions of certain metabolites, as well as the pathways· of certain biosyntheses.A technique termed "inhibition analysis" has been applied in a series of papers by Shive and his co-workers to the study of the effect of a number of antagonists on bacterial growth (8 to 16). The procedure is based on the assumption that, if a metabolic inhibitor blocks a particular reaction and thus limits bacterial growth, addition of the product of the blocked reaction should permit growth. At higher concentrations of the antagonist, a second reaction may be inhibited, whereupon the addition of the product of the second reaction then still further reduces the sen sitivitity of the organism to the inhibitor.· A number of agents other than the competing metabolite itself may reverse the inhibiting effect of a metabolic antagonist, each giving characteristic changes in the inhibition index and showing characteristic competitive or noncompetitive behavior (16).That too facile interpretation of the results of inhibition analysis is possible was pointed out by Hitchings et al. (17), when. it was observed that an entirely abnormal compound, S-bromouracil, was implicated as a metabolic product of a reaction in the growth of Escherichia coli inhibited by S-nitrouracil. Other difficulties m 1 Annu. Rev. Biochem. 1949.18:535-558. Downloaded from www.annualreviews.org Access provided by University of California -Davis on 02/03/15. For personal use only. Quick links to online content Further ANNUAL REVIEWS Annu. Rev. Biochem. 1949.18:535-558. Downloaded from www.annualreviews.org Access provided by University of California -Davis on 02/03/15. For personal use only. Annu. Rev. Biochem. 1949.18:535-558. Downloaded from www.annualreviews.org Access provided by University of California -Davis on 02/03/15. For personal use only.