5_glycogen fatty acid synthesis
DESCRIPTION
HKU science lecture notesTRANSCRIPT
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Key metabolic events in fed & fasted states
Fed state:
Control glycemia – prime importance
Replenish liver glycogen
Generate reducing equivalents for ATP production via ETC
Convert extra CHO to fatty acids & transfer for storage
Clear dietary lipids into various organs
Deaminate amino acids and produce urea
Fasted state:
Main blood glucose level
Increase hepatic glucose output
Use more muscle amino acids for glucose production
Mobilize fatty acids from storage
Increase ketone bodies provision during prolong fasting
2
ATP & NADH
are modulators
of carbon flow
Glycogen – •depot for glucose storage
•glycogenesis occurs in the cytosol
Branched structure of glycogen showing
different glycosidic bonds
Lippincott’s Illustrated Reviews: Biochemistry, 2011
3
Non-reducing ends
α (16) linkage
Advantages of branching in glycogen for it as a storage form of glucose:
1) it is more soluble than the unbranched form.
2) the exposure of more C4 (nonreducing) ends means that glycogen
can be both synthesized and degraded more quickly than a single
starch chain with the same number of residues.
Reducing sugars
Has an open-chain form with an aldehyde group or a free hemiacetal
group. These part of a molecule containing the free anomeric carbon
is called the reducing end.
A non-reducing sugar, therefore, has its anomeric carbon locked in a
ring conformation; the -OH on its end cannot therefore form a ketone
or aldehyde to allow the sugar to act as a reducing agent.
Equilibrium between cyclic and open-chain form in one ring of maltose
Examples: glucose, fructose, galactose, lactose and maltose
4
Glycogen synthase Glycogen phosphorylase
Interconversion of G 6-P and
G 1-P by phosphoglucomutase
Glucose 1-phosphate is attached to uridine diphosphate
(UDP) by UDP-glucose pyrophosphorylase.
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(an enzyme, autoglucosylation)
Glycogen synthesis - Glycogenin is an enzyme which is an acceptor of UDP-
glucose and starts glycogenesis when there is no glycogen fragment (autoglucosylation).
With a few glucose, it becomes a primer and could further elongate by glycogen synthase.
Opposing effects of insulin and
glucagon in glycogen metabolism
Allosteric regulation of glycogen synthesis in liver
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PNAS 100:5578-80, 2003
Alternate flow
of carbon after
a meal
Carbon flow
into mitochondria
for TCA after eating
Glucose
Pyruvate
*
*
*
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Pyruvate dehydrogenase: bridging glycolysis to TCA cycle
www.bmb.leeds.ac.uk/.../metabol/2120lec3.htm
PDH
ADP (+)
NADH & AcCoA (-)
Regulation of pyruvate dehydrogenase complex
Lippincott’s Illustrated Reviews: Biochemistry, 2011
8
Regulatory sites of TCA cycle: isocitrate dehydrogenase
α-ketoglutarate dehydrogenase complex
Metabolic control of the TCA cycle
Direction of
equilibrium
Production of reduced coenzymes,
ATP and CO2 in the TCA cycle
Inhibitors and activators of the TCA cycle
**
9
Carbon flow from glucose into fatty acid
via de novo fatty acid synthesis
Production of cytosolic acetyl CoA Allosteric regulation of malonyl CoA
synthesis by acetyl CoA carboxylase
(allosteric)
Covalent regulation (phosphorylation) of Acetyl CoA carboxylase
by AMP-dependent kinase (AMPK), which itself is regulated both
covalently and allosterically.
Another short-term
regulation of activity
via reversible
phosphorylation
cAMP-dependent
mechanism
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Interrelationship between glucose metabolism and palmitate synthesis
De novo synthesis of
palmitate (16:0) by
fatty acid
synthase complex