Metabolism enzyme regulation

Nebert, D. W. Proposed role of drug-metabolizing enzymes regulation of steady state levels of the ligands that effect growth, homeostasis, differentiation, and neuroendocrine functions. Mol. Endocrinol. 1991, 5(9), 1203-1214. 

Sharkawy, A. M., Abdcl-Rahman, S. Z Hasttan, A. A., Gabr. M. H., el-Zoghby, S. M., and El-Sewedy, S. M. (1994). Biochemical effects of some insecticides on the metabolic enzymes regulating glutathione metabolism. Bull. Environ. Contain. Toxicol. 52, 505-510. 

Hundreds of metabohc reac tions take place simultaneously in cells. There are branched and parallel pathways, and a single biochemical may participate in sever distinct reactions. Through mass action, concentration changes caused by one reac tion may effect the kinetics and equilibrium concentrations of another. In order to prevent accumulation of too much of a biochemical, the product or an intermediate in the pathway may slow the production of an enzyme or may inhibit the ac tivation of enzymes regulating the pathway. This is termed feedback control and is shown in Fig. 24-1. More complicated examples are known where two biochemicals ac t in concert to inhibit an enzyme. As accumulation of excessive amounts of a certain biochemical may be the key to economic success, creating mutant cultures with defective metabolic controls has great value to the produc tion of a given produc t. 

Regulation of enzyme activity is achieved in a variety of ways, ranging from controls over the amount of enzyme protein produced by the cell to more rapid, reversible interactions of the enzyme with metabolic inhibitors and activators. Chapter 15 is devoted to discussions of enzyme regulation. Because most enzymes are proteins, we can anticipate that the functional attributes of enzymes are due to the remarkable versatility found in protein structures. 

Thomas S, Fell DA. The role of multiple enzyme activation in metabolic flux control. Advan Enzyme Regul 1998 38 65-85. 

Don t get the impression that proteins need to be as stable as possible and that the unfavorable interactions are necessarily bad. Proteins shouldn t live forever. A good bit of metabolism is regulated by increasing and decreasing the amount of a specific enzyme or protein that is available to catalyze a specific reaction. If a protein were too stable, it might not be possible to get rid of it when necessary. 

The regulation of drug-metabolizing enzymes by PXR is involved in clinical drug-drug interactions, in which one drug accelerates the metabolism of a second medicine and may change or cause adverse results. Because CYP enzymes can... 

The human placenta expresses a number of nutrient and efflux transporters, as well as metabolic enzymes. Information about the placental function and regulation of these systems, and how they interact with the administered drug, can help to target them appropriately so as to limit fetal exposure to harmful substances. 

It should be noted that HATs and HDACs are not only limited to histones, but rather various nonhistone proteins can be acetylated/deacetylated as well [2, 4]. Many regulators of DNA repair, recombination and replication, viral proteins, classic metabolic enzymes (e.g. bacterial and mammalian acetyl-CoA synthases) and... 

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