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Glycogen metabolism and the pentose phosphate pathway (glycogen breakdown,…
Glycogen metabolism and the pentose phosphate pathway
glycogen breakdown
1 enzyme to degrade glycogen
glycogen phosphorylase
cleaves its substrate by the addition of Pi to yield glucose 1-phosphate from the non-reducing end
glucose 1-phosphate released from glycogen can be readily converted into glucose 6-phosphate by the enz. phosphoglutomutase
phosphorylase is regulated by allosteric interactions and reversible phosphorylation
2 enz. to remodel glycogen so that it remains a substrate for degradation
transferase
shifts a block of 3 glucosyl residues from one outer branch to another
alpha-1,6-glucosidase
"debranching enzyme" = hydrolyzes the alpha-1,6-glycosidic bond, resulting in the release of a free glucose molec.
1 enz. to convert the breakdown into a form suitable for further metabolism
phosphoglucomutase
a phosphoryl group is transferred from the enz. to the substrate, a different phosphoric group is transferred back to restore the enz. to its initial state
liver contains glucose 6-phosphatase, a hydrolytic enz. absent from muscle
the liver releases glucose into the blood during muscular activity and between meals
in contrast with unmodified glucose, however, the phosphorylated glucose is not transported out of cells
glycogen synthesis
utilize UDP-glucose pathway rather than glucose 1-phosphate as the activated glucose donor
UDP-glucose is synthesized from glucose 1-phosphate and UTP. the reaction is catalyzed by UDP-glucose pyrophosphorylase
3 enz.
glycogen synthase
catalyzes the transfer of glucose from UDP-glucose to a polysac. chain already containing more than 4 residues
key regulatory in glycogen synthesis
glycogenin
enz. that catalyzes the formation of alpha-1,4-glucose polymers of 10-20 units
branching enz.
catalyzes the transfer of typically 7 residues to a more interior site. the block of 7 or so residues must include non reducing terminus nad come from a chain at least 10 residues long
Pentsoe pathway
NADPH is key product of light reaction
it's the source of biosynthetic reducing power in all organism and use in a host of biochemical processes
2 phases
the oxidative generation of NADPH
non oxidative interconversions of glucose
requiring NADPH because of 2 reasons
synthesis
fatty acid biosynthesis, cholesterol biosynthesis, neurotransmitter biosynthesis, nucleotide biosynthesis
detoxification
reduction of oxidize glutathione cytochrome P540 monooxygenase
glycogen and PPP are coordinately controlled
glucose 6-phosphate is metabolized by both the glycolytic pathway and the pentose phosphate pathway
how importance
the rate of the PPP is controlled by the conc. of NADP+
the fate of G6P depends on the need ffor NADPH, ribose 5P and ATP
the need for ribose 5P is greater than the need for NADPH
the needs for NADPH and ribose 5P is balance
both NADPH and ATP are required
glucose 6P dehydrogenase lessens oxidative stress
G6P dehydrogenase deficiency causes a drug-induced hemolytic ane,ia
malaria medication : pamaquine, primaquine and vicine should not be given to individuals with G-6PD