Bke2 Biochemistry Lectures

Lecture 18: Glucose metabolism
Reading material: Horton, chapter 14

Abstract:
Glycogen
Glycogen is the main storage polysaccharide of animal cells. Glycogen is a polymer of ( a-1- 4) -linked subunits of glucose, with (a1 - 6) linked branches. Glycogen is especially abundant in liver and skeletal muscle.

Glycogen breakdown and synthesis are reciprocally regulated by several hormones. Insulin, for example, induces the synthesis of glycogen. Glucagon and epinephrine, in contrast, trigger the breakdown of glycogen. The hormones controlling glycogen breakdown and synthesis act through similar mechanisms involving protein kinases and phosphatases. Glucagon, for example, binds to a receptor in the plasma membrane which activates adenylate cyclase. Adenylate cyclase then catalyses the formation of cAMP which in turn activates a protein kinase (protein kinase A). (Remember that kinases add phosphate groups to proteins whereas phosphorylases dephosphorylate them).

The protein kinase phosphorylates the phosphorylases involved in the breakdown of glycogen thereby activating them. The same protein kinase also phosphorylates the glycogen synthase, which incativates it, thereby further assuring that glycogen is not being synthesised while it is being degraded.

The changes in enzymatic activity produced by protein kinases are reversed by protein phosphatases. Insulin stimulates the synthesis of glycogen by activating the enzyme protein phosphatase which dephosphorylates glycogen synthase (which makes the enzyme active). Glycogen breakdown is simultaneously inhibited since dephosphorylation makes the enzymes involved in glycogen breakdown inactivated.

Gluconeogenesis
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 erythrochytes.

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.

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