Regulable enzymes kinetic properties

We begin with descriptions of the properties of enzymes and the principles underlying their catalytic power, then introduce enzyme kinetics, a discipline that provides much of the framework for any discussion of enzymes. Specific examples of enzyme mechanisms are then provided, illustrating principles introduced earlier in the chapter. We end with a discussion of how enzyme activity is regulated. 

In order to understand the regulation of the TCA cycle, it is necessary to look at the AG values for the various reactions and the kinetic properties of the enzymes. Values for the non-equilibrium reactions are tabulated below as Table 9.4 ... 

The human body is composed of a number of different cell types that perform specific functions unique to that cell type and synthesize only the proteins consistent with their functions. Because regulation matches function, regulatory enzymes of pathways usually exist as tissue-specific isozymes with somewhat different regulatory properties unique to their function in different cell types. For example, hexokinase and glucokinase are tissue-specific isozymes with different kinetic properties. 

Regulation in tumor cells appears to allow more efficient conversion of IMP to AMP. The level of the synthetase is increased from 1.6- to 3.7-fold in a number of tumors irrespective of growth rate (23). The kinetic properties of the acidic isozymes from Walker 10) and Novikoff 45) tumors indicate decreased inhibition by AMP. The Km for IMP is decreased for the Novikoff enzyme while the Km for aspartate is increased 45). These changes would favor AMP synthesis as compared to nonneoplastic cells. 

An intricate system of interrelated control mechanisms regulate biochemical reaction sequences. Metabolic pathways are controlled not only by specific activity and inherent kinetic properties of enzymes in the pathway but also by the intracellular concentration of certain essential substrates, activators or inhibitors. PP-ri-bose-P is an essential substrate of purine, pyrimidine and pyridine biosynthesis. The intracellular concentration of PP-ribose-P represents a balance between its synthesis by PP-ribose-P synthetase and its utilization which is catalyzed by several different phosphori-bosyltransferase (PRT) enzymes as well as non-specific phosphatases. Alterations in the rate of synthesis or degradation of PP-ribose-P, whether drug induced or secondary to an inborn error, could potentially change the intracellular concentration of this compound. 

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