BMS2021 Lecture Notes - Lecture 4: Allopurinol, Malic Acid, Methotrexate

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Week 2. Glucose homeostasis and nitrogen
metabolism
MAINTENANCE OF GLUCOSE HOMEOSTASIS II
Achieved by regulating glycogen metabolism
o Liver: glycogen synthesis takes place in the fed state while glycogenolysis accelerates
during fasting
o Muscle: glycogenolysis occurs during exercise and glycogen synthesis begins when at
rest
Achieved at two levels:
o (1) Allosteric regulation of glycogen synthase and glycogen phosphorylase
o (2) Pathways of synthesis and breakdown are hormonally regulated
Glycogen granules may not be seen after sleep/fasting and during exercise in muscles
(~55,000 glucose units attached)
Glycogenolysis:
o Glucose residues are removed from glycogen by Glycogen Phosphorylase
-GP removed Glucose-1-phosphate (G-1-P)
-a’t at at ahig points, comes back when branch is hydrolysed
-when glucose levels return to normal, glucose enters liver cell and binds to allosteric
site on phosphorylase to inhibit the enzyme -> less glycogen breakdown
o G-6-P is dephosphorylated in the liver for transport out
-Glucose-6-phosphatase is seuesteed i edoplasi etiulu esues live does’t
use up glucose for its own needs)
o Control of glycogen breakdown: Glucagon/epinephrine signalling pathway
-starts phosphorylation cascade via cAMP -> causes phosphorylation of phosphorylase ->
breakdown of glycogen
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Glycogen synthesis:
o Glycogen is synthesised by Glycogen synthase (energy storage)
o Controlled by phosphorylation
o Also controlled by insulin-signalling pathway
-increases glucose import into muscle -> stimulates muscle hexokinase ->enables
activation of glucose
-activates glycogen synthase (phosphorylated = inactive)
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Regulation of glycogen synthesis and breakdown:
o Kinase and phosphatase are reversible
-can inhibit or activate
o Kinase phosphorylates = inactivated
o Phosphatase dephosphorylates = active
o Phosphorylase activated = breakdown
Coordination and control of carbohydrate metabolism
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Document Summary

(cid:272)a(cid:374)"t a(cid:272)t at (cid:271)(cid:396)a(cid:374)(cid:272)hi(cid:374)g points, comes back when branch is hydrolysed. When glucose levels return to normal, glucose enters liver cell and binds to allosteric site on phosphorylase to inhibit the enzyme -> less glycogen breakdown: g-6-p is dephosphorylated in the liver for transport out. Glucose-6-phosphatase is se(cid:395)ueste(cid:396)ed i(cid:374) e(cid:374)doplas(cid:373)i(cid:272) (cid:396)eti(cid:272)ulu(cid:373) (cid:894)e(cid:374)su(cid:396)es live(cid:396) does(cid:374)"t use up glucose for its own needs: control of glycogen breakdown: glucagon/epinephrine signalling pathway. Starts phosphorylation cascade via camp -> causes phosphorylation of phosphorylase -> breakdown of glycogen: glycogen synthesis, glycogen is synthesised by glycogen synthase (energy storage, controlled by phosphorylation, also controlled by insulin-signalling pathway. Increases glucose import into muscle -> stimulates muscle hexokinase ->enables activation of glucose. Activates glycogen synthase (phosphorylated = inactive: regulation of glycogen synthesis and breakdown, kinase and phosphatase are reversible. Can inhibit or activate: kinase phosphorylates = inactivated, phosphatase dephosphorylates = active, phosphorylase activated = breakdown, coordination and control of carbohydrate metabolism. Deamination: release of an amino group, glutamate dehydrogenase.

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