Gluconeogenesis function

Gluconeogenesis makes glucose from pyruvate to help maintain blood glucose levels. 

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U (No CaM) < O Q. CL Heart, kidney, Brain, liver, widespread Cardiac function, Ca2+-dependent regulation, hormonal regulation of gluconeogenesis, cell proliferation, coincidence detector for NO... 

Under certain circumstances, and very rarely, the inhibition of gluconeogenesis by metformin may suppress lactic acid metabolism and precipitate a potentially fatal lactic acidosis. Impairment of renal function, liver disease, alcoholism, conditions that give rise to increased lactate production (e.g. congestive heart failure, infections) are therefore contraindications for the application of metformin. 

In relatively recent years, it has become clear that under-nntrition of mother leads to low birth weight of the baby and this can increase the risk of development of degenerative disease in later life, e.g. hypertension, obesity, type 2 diabetes. One hypothesis is that the foetus adapts meta-bolically to deficiencies by increasing the number of cells in organs that perform specific functions that can overcome the deficiency, e.g. an increase in the number of liver cells that carry out gluconeogenesis, an increase in cells in the adrenal cortex to produce more of the chronic stress hormone, cortisol. These changes are carried over into adnlthood which can lead to an inadequate response of the liver to insulin so that insulin resistance develops. So far, however, it is unclear whether deficiencies in specific nntrients or undemutrition per se are responsible for snch changes (Chapter 15). 

Fructose 2,6-bisphosphate (Fru-2,6-bP) plays an important part in carbohydrate metabolism. This metabolite is formed in small quantities from fructose 6-phosphate and has purely regulatory functions. It stimulates glycolysis by allosteric activation of phosphofructokinase and inhibits gluconeogenesis by inhibition of fructose 1,6-bisphosphatase. 

Metformin Obscure Reduced hepatic and renal gluconeogenesis Decreased endogenous glucose production Type 2 diabetes Oral maximal plasma concentration in 2-3 h Toxicity Gastrointestinal symptoms, lactic acidosis (rare) cannot use if impaired renal/hepatic function congestive heart failure (CHF), hypoxic/acidotic states, alcoholism... 

In this chapter we describe the individual reactions of glycolysis, gluconeogenesis, and the pentose phosphate pathway and the functional significance of each pathway. We also describe the various fates of the pyruvate produced by glycolysis they include the fermentations that are used by many organisms in anaerobic niches to produce ATP and that are exploited industrially as sources of ethanol, lactic acid, and other... 

The standard free-energy change for this reaction is quite high, but under physiological conditions (including a very low concentration of oxaloacetate) AG 0 and the reaction is readily reversible. Mitochondrial malate dehydrogenase functions in both gluconeogenesis and the citric acid cycle, but the overall flow of metabolites in the two processes is in opposite directions. 

Pllkls, S.J. Claus, T.H. (1991) Hepatic gluconeogenesis/ glycolysis regulation and structure/function relationships of substrate cycle enzymes. Annu. Rev. Nutr. 11, 465-515. 

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