The Limits of Enzyme Specificity and the Evolution of Metabolism. Issue 12 (December 2018)

• Record Type: Journal Article
• Authors: Peracchi, Alessio
• Is Part Of: Trends in biochemical sciences. Volume 43:Issue 12(2018)
• Page Start: 984
• Page End: 996
• Publication Date: 2018-12
• Subjects: substrate specificity -- substrate promiscuity -- chemicophysical limits -- metabolite repair enzymes -- underground metabolism; Biochemistry -- Periodicals; 572
• DOI: 10.1016/j.tibs.2018.09.015
• Languages: English
• ISSNs: 0968-0004

Abstract

Abstract : The substrate specificity of enzymes is bound to be imperfect, because of unavoidable physicochemical limits. In extant metabolic enzymes, furthermore, such limits are seldom approached, suggesting that the degree of specificity of these enzymes, on average, is much lower than could be attained. During biological evolution, the activity of a single enzyme with available alternative substrates may be preserved to a significant or even substantial level for different reasons – for example when the alternative reaction contributes to fitness, or when its undesirable products are nevertheless dispatched by metabolite repair enzymes. In turn, the widespread occurrence of promiscuous reactions is a consistent source of metabolic 'messiness', from which both liabilities and opportunities ensue in the evolution of metabolic systems. Highlights: Substrate specificity cannot be absolute and is inherently limited. The maximum capacity to discriminate between alternative substrates can be relatively low, and in any case it is seldom approached owing to evolutionary constraints. In some enzymes of primary metabolism, substrate promiscuity is favored, although this may interfere with high flux and efficient regulation. In other cases, enzymes acting on alternative substrates generate toxic or useless products; however, these can be destroyed or recycled by repair enzymes. The limited substrate specificity of enzymes often results in the production of non-standard metabolites which contribute to the complexity of the metabolome. Substrate promiscuity helps to fuel an 'underground' network of reactions which may represent a basis for further evolution and diversification of metabolism.