Transcript 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: Lippincott’s 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 a 1-> 4
with branch points in the chain that are
a 1-> 6 and occur at an average
spacing of 8 to 12 a 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 3’5’-cyclic AMP which activates protein
kinase A.
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© 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