KE7001 Biochemistry Lectures

Pentose phosphate pathway. Glycogen

Reading material: Stryer, Chapter 20.3-5, 21

Abstract:

The pentose phosphate pathway (PPP) consists of two phases: the oxidative degeneration of NADPH and the non oxidative interconversion of sugar. NADPH is generated when glucose 6-phosphate is oxidised to ribose 5-phosphate. This five carbon sugar and its derivatives are components of RNA and DNA and several other components. NADPH produced by the PPP is used as reducing substrate for reductive processes such as fatty acid synthesis and to regenerate reduced glutathione, for example in red blood cells. The pentose phosphate pathway is linked to glycolysis by transketolases and transaldolases.

Glycogen is the main storage polysaccharide of animal cells. Glycogen is a polymer of (alpha-1,4)-linked subunits of glucose, with (alpha-1,6)-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.

Links:
Stryer: Glycogen Phosphorylase (Structural insight, use Netscape/Chime)
Stryer: Chapter 21 Living figures (Use Netscape/Chime)

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