BIOC/DENT/PHCY 230 LECTURE 9. Carbohydrate metabolism in the fasted state o the body needs to ensure...
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Transcript of BIOC/DENT/PHCY 230 LECTURE 9. Carbohydrate metabolism in the fasted state o the body needs to ensure...
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BIOC/DENT/PHCY 230
LECTURE 9
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Carbohydrate metabolism in the fasted state
the body needs to ensure there is a constant supply of glucose for tissues like the brain
this can be achieved by mobilising body stores of glucose (glycogenolysis) or synthesising glucose de novo (gluconeogenesis)
the stimulation for the mobilisation and/or synthesis of glucose can come from a number of sources
glucagon, adrenaline and cortisol can all increase the mobilisation of glucose
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Glycogen mobilisation
the two main stores of glycogen are muscle and liver
muscle glycogen is for local use
liver glycogen helps maintain plasma glucose levels
the branched nature of glycogen allows for the rapid mobilisation of glucose from these stores under the appropriate conditions
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What are the chemical requirements for glycogen
mobilisation? glycogen contains two types of bond:
-1,4 and -1,6 glycosidic bonds
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Glycogenolysis requires three different enzyme activities
1) an -1,4 glucosidase activity
2) an -1,6 glucosidase activity
3) an -1,4 -1,4 glucantransferase activity
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Glycogen phosphorylase catalyses the cleavage of the -1,4 glycosidic bonds
non-reducing end
glucose-1-phosphate
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Glycogen phosphorylase can not digest all of the glucose units in a branch GP can only cleave down to
4 or 5 residues from a branch point
to allow the process to continue a “debranching enzyme” is required
this enzyme has both-1,6 glucosidase activity and-1,4 -1,4 glucantransferase activity
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Glucose-1-phosphate must be converted to glucose-6-phosphate
before it can enter glycolysis
catalysed by phosphoglucomutase
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Regulation of glycogenolysis
glycogen phophorylase can be regulated both by covalent modification and allosteric interactions
glycogen phosphorylase is found in two “active forms”
phosphorylase a is relatively active
phosphorylase b is relatively inactive (but still active none the less)
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AMP
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Glucagon stimulates glycogen phosphorylase via a receptor mediated signalling pathway
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A closer look at the activation of adenylate cyclase
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phosphodiesterase
phosphatase
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Co-ordinate regulation of glycogenolysis and glycogen
synthesis both glycogenolysis and glycogen synthesis occur in the cytosol
both pathways have G-6-P and G-1-P as intermediates
need some mechanism to only have one pathway active at any one time
Those signals which activate glycogen phosphorylase inhibit glycogen synthase