01:694:301 Lecture 21: Chapter 21 – ‘Glycogen Metabolism’ Revised

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Chapter 21‘Glycogen Metabolism’
Glucose is stored as a nonosmotically active polymer called glycogen
o Glycogen is
a readily mobilized storage form of glucose
o It is a large branched polymer of glucose residues that can be broken down to yield
glucose when energy is needed
! It is made of approx. 12 layers glucose molecules (as large as 40nm)
! Most of these residues are linked by α-1, 4–glycosidic linkages
! Branched at about every 10th residues α -1, 6–glycosidic linkages
o Doesn’t have as much energy as fatty acids; not as reduced
o Blood-glucose concentration maintained by glycogen " glucose
! Keeps brain fueled; which solely relies on glucose as fuel source
o This glucose is also provides energy during strenuous activities in absence O2
KNOW the structure of glycogen, and that it is found in the cyto of both liver/muscle cells.
o [] higher in liver but more is stored in muscle due to it’s greater mass
o Liver – maintain blood-glucose levels; meeting energy need entire cell
o Muscle regulated to meet energy need of muscle alone
KNOW that an average person has about 28 Cal of liver glycogen, 480 Cal of muscle glyc.
o One nutritional ‘Calorie’ equals one biochemical ‘kilocalorie’ (not in chapter)
o What do these numbers imply about the functions of glycogen in the body?
Glucose-6-phosphate is at a metabolic crossroad—KNOW the various ways that it can be
used (Fig. 21.4)
o G6P has three different fates: (1) Initial substrate for glycolysis; (2) Conversion into free
glucose for release bloodstream; (3) Processed by PPP " NADPH and ribose
The breakdown of glycogen involves the following:
o (a)
releasing glucose 1-P
o (b)
of glycogen for further breakdown, and
o (c)
glucose 1-P into glucose-6-P
Through allosteric responses, enzyme activity is adjusted to meet cell needs of cell
Regulation by hormones adjust glycogen metabolism to meet needs entire organism
Glycogen Phosphorylase is a complex and interesting enzyme which is discussed in chap.
o It is the key enzyme in breakdown of glycogen
o It cleaves its substrate by addition of Pi " glucose 1-P (
o Phosphorylase catalyzes removal glucosyl residues from non-reducing ends of glycogen
(free –OH group C-4 end)
o Orthophosphate (Pi) splits glycosidic linkage b/w C-1 of terminal residue and adjacent C-4
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! Note that α C-1 configuration retained
o Phosphorlysis proceeded toward glycogen breakdown due to ratio Pi : glucose 1-P > 100
o This cleavage is ‘energetically advantageous’ " released sugar is already phosphorylated
o Other advantage for muscle cells is that G-1P doesn’t have transporters; can’t leave cell
o Note: Hydrolytic cleavage would give glucose (which would need to be phosphorylated to
enter glycolytic pathway – cost of ATP)
o Phosphorolysis requires an enzyme with an active site that excludes water, otherwise
hydrolysis would occur instead
! Phosphorylase is dimer containing 2 subunits:
carboxyl terminal domains
Amino terminal contains glycogen binding site which located in deep crevice
! The mechanism used to exclude water includes the following:
Carbonium ion intermediate
which is formed from glucose residue
This enzyme also requires the coenzyme pyridoxal phosphate (PLP)
o PLP forms Schiff-base linkage with lys side chain of phosphorylase
o 5’ phosphate group of PLP acts w/ Pi by serving as H+ donor/acceptor
! Pi donates H+ O attached to C-4 of glycogen while simultaneously
getting H+ from PLP
o Carbonium ion is then attacked Pi " G-1P (H+ returned to PLP)
o Note: separation b/w binding and catalytic site allows enzyme to phosphorylate many
residues w/o having to dis/re-associate after catalysis "
processive enzyme’
The remodeling is done by a bifunctional enzyme (in eukaryotes)—transferase and
debranching enzymes (619-620)
o After the release of 6 gluc per branch, phosphorylase halts…other enzymes are needed to
cleave α–1, 6–glycosidic linkages:
debranching (
–1,6 glucosidase
! These enyzmes (remodel) glycogen convert branched structure to linear paving the
way for further cleavage by phosphorlyase
o Transferase shifts block of 3 glucosyl residues from outer branch to another branch
! After this transfer, exposed glucose residue is hydrolyzed by debranching enzyme
o Note that the free glucose released by debranching enzyme represents about 10% of the
glucose released from catabolism of normal glycogen
Phosphoglucomutase converts Glucose 1-P into G6P
o This ‘mutase’ enzyme exchanges P-group with the substrate
o The catalytic site of active mutase contains a phosphorylated serine residue
! The P-group from serine is transferred to C-6 hydroxyl group " G-1, 6 BP
! The P-group on C-1 of intermediate is then put on serine residue " G6P and
regenerates enzyme
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