Enzyme Group Evaluation

Methods for evaluating the status of enzymes in the glycolytic cycle in red cell hemolysates have been described using simple fluorescence spot tests which allow detection of enzyme defects in a group of enzymes, with determination of the speciflc defect deferred until later and applied only to those individuals found to be abnormal by the screening methods employed (Yunis, 1973). 

While this does not constitute an exhaustive survey of the status of scanning for disease-associated and/or genetic defects, it is sufficient to show that some of the tools are at hand to allow the evaluation of many different possible indicator substances for inclusion in screening tests. 

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Rossi and Bernhard (1971) attempted to show the close relation between catalysis and the conformational variations of an enzyme molecule. Their study indicated that the rate of nucleophile-catalyzed hydrolysis of an acyl chymotrypsin (the o-/ -(3-indole)-acryloyl]-Ser 195-chymotrypsin), is the same as the rate of denaturation of the acyl enzyme when evaluated from the optical properties of the acyl group in the enzyme. Thus, Rossi and Bernhard (1971) concluded that a covalently modified acyl enzyme-nucleophile complex is an obligatory intermediate in both catalysis and denaturation of this acyl enzyme. 

Bartlett P A and C K Marlowe 1987. Evaluation of Intrinsic Binding Energy from a Hydrogen-bondi Group in an Enzyme Inhibitor. Science 235 569-571. 

These must be worthwhile objectives and the recent identification by a number of research groups (see Skovronsky and Lee 2000 for description and details) of P-secretase as the membrane-bound aspartyl protease (RACE), S-site APP cleaving enzyme, paves the way for developing possible chemical inhibitors of its activity for experimental and clinical evaluation, although that remains for the future. 

The study of both carbonyl and carbon acid participation in ester hydrolysis has been used by Bowden and Last (1971) to evaluate certain of the factors suggested for important roles in enzymic catalysis. A first model concerns a comparison of the three formyl esters and shows that the proximity of the formyl to the ester group and internal strain increase in passing along the series, 1,2-benzoate, 1,8-naphthoate and 4,5-phenanthroate. The very large rate enhancements result from the proximity of the internal nucleophile once formed and from internal strain. Strain is increased or induced by the primary... 

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