Wednesday 25 January 2017

Gluconeogenesis, the Pentose Phosphate Pathway and Glycogen Metabolism


GLYCOGEN METABOLISM
Glycogen stored in muscle and liver cells.
Important in maintaining blood glucose levels.
Glycogen structure: 1,4 glycosidic linkages with 1,6 branches.
Branches give multiple free ends for quicker breakdown or for more places to add additional
units.
Glycogen Degradation
Glucose residues of starch and glycogen released through enzymes called starch
phosphorylases and glycogen phosphorylases.
Catalyze phosphorolosis:
polysaccharide +Pi ---> polysaccharide(n-1) + glucose 1-phosphate
Pyridoxal phosphate (PLP) is prosthetic group in active site of enzyme; serves as a proton
donor in active site.
Allosterically inhibited by high [ATP] and high [glucose 6-phosphate].
Allosterically activated by high [AMP].
Sequentially removes glucose residues from nonreducing ends of glycogen, but stops 4
glucose residues from branch point --> leaves a limit dextran.
Limit dextran further degraded by glycogen-debranching enzyme (glucanotransferase
activity) which relocated the chain to a free hydroxyl end.
Amylo-1,6-glucosidase activity of debranching enzyme removes remaining residues of
chain.
This leaves substrate for glycogen phosphorylase.
Each glucose molecule released from glycogen by debranching enzyme will yield 3 ATPs in
glycolysis.
Each glucose molecule released by glycogen phosphorylase will yield 2 ATPs in glycolysis.
Why?
_ ATP not needed in first step because glucose 1-phosphate already
formed.
phosphoglucomutase
glucose 1-phosphate ----------------------> glucose 6-phosphate
1) In liver, kidney, pancreas, small intestine,
glucose 6-phosphatase
glucose 6-phosphate --------------------------> glucose + Pi
2
Glycogen Synthesis
Not reverse of glycogen degradation because different enzymes are used.
About 2/3 of glucose ingested during a meal is converted to glycogen.
First step is the first step of glycolysis:
hexokinase
glucose --------------> glucose 6-phosphate
There are three enzyme-catalyzed reactions:
phosphoglucomutase
glucose 6-phosphate ---------------------> glucose 1-phosphate
glucose 1-phosphate ---------------> UDP-glucose (activated form of glucose)
glycogen synthase
UDP-glucose ----------------------> glycogen
Glycogen synthase cannot initiate glycogen synthesis; requires preexisting primer of
glycogen consisting of 4-8 glucose residues with (1,4) linkage.
Protein called glycogenin serves as anchor; also adds 7-8 glucose residues.
Addition of branches by branching enzyme (amylo-(1,4 --> 1,6)-transglycosylase).
Takes terminal 6 glucose residues from nonreducing end and attaches it via (1,6) linkage
at least 4 glucose units away from nearest branch.

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