Pentose Phosphate Pathway and Fructose Metabolism

Pentose Phosphate Pathway and Fructose Metabolism

DENTAL BIOCHEMISTRY 2015 Lecture 11 PENTOSE PHOSPHATE PATHWAY AND GLYCOGEN METABOLISM Michael Lea LECTURE OUTLINE Functions of the pentose phosphate pathway

Oxidative reactions leading from glucose 6phosphate to ribose 5-phosphate Non-oxidative reactions leading to the formation of intermediates of glycolysis Glycogen structure and function Glycogen synthesis and breakdown Suggested reading: Lippincotts Biochemistry, 6th edition, pages 125-135, 145-155, glycogen

glucose glucose 6-phosphate glycolysis pentose

phosphate pathway FUNCTIONS OF THE PENTOSE PHOSPHATE PATHWAY Provide reduced NADP for synthetic reactions, e.g. fatty acid synthesis and reduction of glutathione

Provide pentose phosphate for nucleic acid synthesis GLYCOGEN FUNCTION AND LOCATION Glycogen serves as a storage form of carbohydrate In a well fed individual the concentration per gram tissue is highest in liver but the glycogen in liver can be depleted by a 24 hour fast.

Glycogen is less readily depleted in muscle and there is more total glycogen in muscle than in any other tissue of the body. Brain has a very low glycogen concentration. The brain is largely dependent upon circulating glucose for the carbohydrate that it requires. GLYCOGEN STRUCTURE Glycogen is a polysaccharide in which

glucosyl residues are joined by glycosidic links. The major linkage between glucosyl residues are 1-> 4 with branch points in the chain that are 1-> 6 and occur at an average spacing of 8 to 12 1 -> 4 links. UDP

glycogen UDP-glucose phosphate glucose 1-phosphate glucose

glucose 6-phosphate glycolysis pentose phosphate pathway

GLYCOGEN SYNTHESIS Glucose 6-phosphate is converted to glucose 1-phosphate in a reversible reaction catalyzed by phosphoglucomutase Glucose 1-phosphate + UTP -> UDP-glucose + pyrophosphate catalyzed by UDP-glucose pyrophosphorylase Glycogen synthase catalyzes the transfer of

glucose from UDP-glucose to glycogen with the formation of an alpha 1-> 4 link. Branch points are formed by glycogen branching enzyme (amylo 1-4 -> 1-6 transglucosylase). GLYCOGEN BREAKDOWN Alpha 1-> 4 links in glycogen are broken by a phosphorolytic cleavage that requires

inorganic phosphate and produces glucose 1phosphate. The reaction is catalyzed by the enzyme glycogen phosphorylase. Branch points are cleaved by a hydrolytic reaction that produces free glucose and is catalyzed by glycogen debranching enzyme. This enzyme also has a transferase activity that can transfer a small oligosaccharide near a branch point to a longer alpha 1-> 4 linked chain.

REGULATION OF GLYCOGEN METABOLISM Glycogen metabolism is regulated by the activities of glycogen synthase and glycogen phosphorylase. Phosphorylation by protein kinases activates glycogen phosphorylase and inactivates glycogen synthase. The phosphorylation is reversed by phosphoprotein phosphatase activity.

Glucagon and epinephrine increase glycogen breakdown by activating adenylate cyclase. This produces 35-cyclic AMP which activates protein kinase A. Downloaded from: StudentConsult (on 4 December 2011 07:14 PM) 2005 Elsevier LECTURE OBJECTIVES

After studying this lecture material you should be able to Describe the functions of the pentose phosphate pathway Distinguish the oxidative and non-oxidative parts of the pentose phosphate pathway Describe glycogen structure and function Distinguish the reactions in glycogen synthesis and breakdown

Describe how regulation of glycogen metabolism involves the phosphorylation status of glycogen synthase and glycogen phosphorylase

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