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

54 views6 pages
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)
Phosphorolysis
releasing glucose 1-P
o (b)
Remodeling
of glycogen for further breakdown, and
o (c)
Changing
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 (
phosphorolysis
)
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
Unlock document

This preview shows pages 1-2 of the document.
Unlock all 6 pages and 3 million more documents.

Already have an account? Log in
! 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:
amino
and
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:
transferase
and
debranching (
α
–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
Unlock document

This preview shows pages 1-2 of the document.
Unlock all 6 pages and 3 million more documents.

Already have an account? Log in

Get OneClass Notes+

Unlimited access to class notes and textbook notes.

YearlyBest Value
75% OFF
$8 USD/m
Monthly
$30 USD/m
You will be charged $96 USD upfront and auto renewed at the end of each cycle. You may cancel anytime under Payment Settings. For more information, see our Terms and Privacy.
Payments are encrypted using 256-bit SSL. Powered by Stripe.