Gluconeogenesis regulatory mechanisms

Uptake of Ca2+ into cells, or release of this ion from intracellular stores, is a major regulatory mechanism in many if not all cells (see Section E). Mn2+ activates phosphoenolpyruvate carboxykinase (Eq. 13-46) and maybe a regulator of gluconeogenesis.142 Iron controls the synthesis of ferritin and of transferrin receptors137 (Chapter 16). The specific metal ions present in many biological macromolecules are likely to participate in additional regulatory processes. 

The expected alteration of the flux through these pathways in response to alteration in nutrient and hormone supply and the redox state of the liver provides us with a useful new probe of the regulatory mechanisms of gluconeogenesis and the health of the liver. Shown in Table II are the relative fluxes of label... 

Other reciprocal regulators of glycolysis and gluconeogenesis are fructose-2,6-bisphosphate and acetyl-CoA. See Figure 16.7 for additional details about the reciprocal regulatory mechanisms of action of fructose-2,6-bisphophate. 

The metabolic network in a cell is a complex and nonlinear system that has evolved for specific functions. This network generally includes central carbon metabolism, energy conversion, secondary metabolite production, transport reactions, regulatory mechanisms, etc. The metabolic networks for many important cell types are well understood and available in the literature [6], However, sometimes a cell or organ system has extensive metabolic capabilities, but only a subset of these functions is active under different conditions. For example, a hepatocyte is capable of both gluconeogenesis and glycolysis, but only one of these metabolic pathways is dominant at any given time. Therefore, the metabolic network is often tailored to best reflect the expected network behavior. 

It may appear peculiar that build-up and breakdown proceed largely via the same route merely a few key reactions differ. These key reactions are probably the targets of the cell s regulatory mechanism, which must determine the direction that the processes are to take. Gluconeogenesis from amino acids (i.e. ultimately out of proteins), for example, is strongly stimulated by the hormone cortisol (cf. Chapt. XX-2). Such regulation is of decisive importance for the organism s over-all metabolism. 

D-Fructose 1,6-diphosphatase is a regulatory enzyme playing a key role in the control of gluconeogenesis. A number of mechanisms have been proposed for the regulation of D-fructose 1,6-diphosphatase activity, including allosteric control by AMP,396 inhibition by D-fructose 1,6-bisphosphate, ADP, or ATP, and modification of the sulfhydryl groups of the enzyme.397,398... 

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