Statistical Time Events in Enzymes: A Physical Assessmen

Abstract

Enzyme action is the result of a large number\nof discrete steps involving a great variety of\nprocesses such as cooperative conformational\nchanges, acid-base catalysis, nucleophylic and/or\nelectrophylic attack from properly positioned\ngroups, etc.; it is widely recognized that in order\nto be useful for catalysis, the various elementary\nprocesses must be space- and time-controlled\nduring enzyme function. In the past decade great\nprogresses have been made in understanding the\nchemistry and the stereochemistry of enzyme\naction, with particular emphasis on the role of the\nspatial effects. Obviously, an analysis of the\ntemporal aspects of enzyme action is equally\nimportant. The ultimate goal is the description of\nthe concomitance and/or sequence of individual\nelementary steps in the catalytic act. This ambitious\nbut difficult goal can be approached by\nfocusing the attention on the time constants of the\nvarious elementary processes and assessing their\nmicroscopic mechanism by comparative studies on\nrepresentative model systems. This approach was introduced in enzymology with the development\nof fast relaxation methods and will be followed in\nthis paper, with the understanding that it suffers\nfrom the same intrinsic limitations as an analysis\nof a musical piece restricted to a list of the sound\nfrequencies occurring in it but devoid of any\ninformation about their temporal sequence and\nrelative intensity.\nOur aims are:\nl. To review time events detected in\nenzymes using a proper physical framework, i.e.,\nthe theory of the random processes.\n2. To identify these events at a molecular\nlevel by comparison with processes occurring in\nappropriate model systems.\n3. To discuss the statistical significance of\nthe detected events.\nWe shall start with the simpler model systems\nand shall then proceed to analyze situations of\nincreasing complexity and eventually consider\nenzyme-substrate complexes. For each class of\nevents some data will be critically reviewed and\ntheir relevance to enzyme catalysis stressed. All data will then be comparatively discussed according\nto their time scale and some mechanistic\nconclusions will be derived.\nThe representative enzymes considered in this\nreview were chosen among those which can work\nas separate entities in an aqueous medium because\nthey are simpler and better known.