KE7001 Biochemistry Lectures

Glycolysis and gluconeogenesis

Reading material: Stryer, Chapter 16

Abstract:

Glycolysis is a universal metabolic pathway for the catabolic conversion of glucose to pyruvate accompanied by the formation of ATP. The process is catalysed by ten cytosolic enzymes, and all of the intermediates are phosphorylated compounds. There is a net gain of two ATP and two NADH per oxidised glucose. Under aerobic conditions, electrons pass from NADH to O₂ through the respiratory chain. The NADH formed in glycolysis must be recycled to regenerate NAD⁺, which is required as electron acceptor. Under anaerobic conditions, many organisms regenerate NAD⁺ by transferring electrons from NADH to pyruvate to form lactate. A variety of hexsoses, including fructose and galactose can be funnelled into glycolysis.

Phosphofructokinase is the most important enzyme for control of glycolysis. The most important factor in the regulation of glycolysis is the concentration of ATP.

Gluconeogenesis is the formation of carbohydrate from noncarbohydrate precursors, the most important of which are pyruvate, lactate, and alanine. In vertebrates, gluconeogenisis in the liver and kidney provide glucose for use by the brain, muscle and erythrocytes.

Three irreversible steps in the glycolytic pathway cannot be used in gluconeogenisis in the cell, and these are bypassed by reactions catalysed by non-glycolytic enzymes. Conversion of pyruvate to phosphoenolpyruvate involves several enzymes. Dephosphorylation of fructose-1,6-phosphate is catalysed by fructose-1,6-bisphosphatase, and dephosphorylation of glucose 6-phosphate by glucose-6-phosphatase. Formation of one molecule glucose from pyruvate requires four molecules of ATP and two of GTP.

Gluconeogenesis and glycolysis are reciprocally regulated. Glycolysis is stimulated and gluconeogenesis is inhibited by high levels of AMP and fructos-2,6-bisphosphate. Citrate, on the other hand, stimulates gluconeogenesis and inhibits glycolysis. Another key control is the allosteric regulation of pyruvate kinase, and the carboxylation of pyruvate.

Links:
Stryer: Energetics of Glucose metabolism (Conceptual insight)
Stryer: Chapter 16 Living figures (Use Netscape/Chime)

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