Regulation of Pathways

It is very seldom that only a single substrate is present. It is therefore important to examine how the regulation of degradative pathways may be affected and, in particular, whether the simultaneous presence of other contaminants has an adverse effect. In addition, some of the components of a contaminant may directly inhibit degradation by toxification of the relevant organism. The example of azaarenes in groundwater at a wood preservation site that inhibit PAH degradation (Lantz et al. 1997) is noted in Chapter 14. 

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Wang W, WyckofF JB, Goswami S et ai. Coordinated regulation of pathways for enhanced cell motility and chemotaxis is conserved in rat and mouse mammary tumors. Cancer Res 2007 67(8) 3505-3511. 

Enzymes nomenclature, kinetics and inhibitors Enzymes and regulation of pathways 69... 

Regulation of enzyme activity Enzymes and regulation of pathways 71... 

Regulation of glycolysis and Krebs cycle Enzymes and regulation of pathways 73... 

Oxidation of fatty acids to produce ATP in muscle and ketone bodies in liver Enzymes and regulation of pathways 75... 

Regulation of lipolysis, p-oxidation, ketogenesis and gluconeogenesis Enzymes and regulation of pathways 77... 

S.K. Wadman, P.K. de Bree, A.H. van Gennip, J.W. Stoop, B.J.M. Zegers and G.E.J. Staal, Urinary purines in a patient with a severely defective T cell immunity and a purine nucleoside phos-phorylase deficiency, "Purine Metabolism in Man-II regulation of pathways and enzyme defects", M.M. Muller, E. Kaiser and J.E. Seegmiller, Plenum Publishing Corporation, New York (1977) pp 471-477. 

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. 

Interestingly, anabolism and catabolism occur simultaneously in the cell. The conflicting demands of concomitant catabolism and anabolism are managed by cells in two ways. First, the cell maintains tight and separate regulation of both catabolism and anabolism, so that metabolic needs are served in an immediate and orderly fashion. Second, competing metabolic pathways are often... 

We turn now to the biosynthesis of lipid structures. We begin with a discussion of the biosynthesis of fatty acids, stressing the basic pathways, additional means of elongation, mechanisms for the introduction of double bonds, and regulation of fatty acid synthesis. Sections then follow on the biosynthesis of glyc-erophospholipids, sphingolipids, eicosanoids, and cholesterol. The transport of lipids through the body in lipoprotein complexes is described, and the chapter closes with discussions of the biosynthesis of bile salts and steroid hormones. 

Interestingly, Gassman and co-workers have demonstrated that the regulation of the induction of AHR by indolo[3,2-/)]carbazole (4) was reduced by prior activation of the hypoxia-inducible expression. As the hypoxia pathways are dependent on ARNT, prior activation may deplete the cell of available ARNT for AHR heterodimerization (97MI3). 

As described in the previous section, bile acids have evolved over the last years from regulators of bile acid homeostasis to general metabolic integrators. It is therefore not too surprizing that a number of bile acid-activated signaling pathways have become attractive targets for the treatment of gallstones and other metabolic diseases, such as obesity, type 2 diabetes, hyperlipidemia, and atherosclerosis. 

Vasopressin (antidiuretic hormone [ADH]) secretion increases in response to decreased blood volume and/or reductions in effective blood volume via a decrease in inhibitory tone from both low-pressure and high-pressure baroreceptors to the hypothalamus. The neuronal pathways that mediate hemodynamic regulation of... 

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