‘Chiral compartmentation’ in metabolism: Enzyme stereo-specificity yielding evolutionary options

Abstract

We introduce the concept of ‘chiral compartmentation’ in metabolism that emerges from the stereo-specificity of enzymes for their substrate(s).The fully differentiated mammalian erythrocyte has no sub-cellular organelles and yet it displays compartmentation of lactic acid that is generated either by glycolysis or the glyoxalase pathway. A form of ‘operational compartmentation’ exists, based not on the chemistry of the reactive groups in the molecules but their stereoisomerism. This we call ‘chiral compartmentation’, and the rationale for its ‘natural selection’ in the erythrocyte (and presumably in the cytoplasm of other cells) is discussed.Increasing awareness of the presence of d-amino acids in proteins in the otherwise dominant ‘l-chiral biosphere’, and of the preferential use of one enantiomer of a metabolite versus the other is largely due to recent developments in rapidly-applicable, analytical–chemical methods. We confirmed that the glyoxalase pathway yields d-lactic acid by using nuclear magnetic resonance (NMR) spectroscopy of stretched chiral hydrogels.The activities of the two lactate-producing pathways have been described by numerical integration of simultaneous non-linear differential equations, based on enzyme models like that introduced by Michaelis and Menten in 1913.