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1 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
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5_Glycogen Fatty Acid Synthesis

Feb 03, 2016

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Chui Wei

HKU science lecture notes
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Page 1: 5_Glycogen Fatty Acid Synthesis

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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

Page 2: 5_Glycogen Fatty Acid Synthesis

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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

Page 3: 5_Glycogen Fatty Acid Synthesis

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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

Page 4: 5_Glycogen Fatty Acid Synthesis

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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.

Page 5: 5_Glycogen Fatty Acid Synthesis

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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

Page 6: 5_Glycogen Fatty Acid Synthesis

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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

*

*

*

Page 7: 5_Glycogen Fatty Acid Synthesis

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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

Page 8: 5_Glycogen Fatty Acid Synthesis

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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

**

Page 9: 5_Glycogen Fatty Acid Synthesis

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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

Page 10: 5_Glycogen Fatty Acid Synthesis

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Interrelationship between glucose metabolism and palmitate synthesis

De novo synthesis of

palmitate (16:0) by

fatty acid

synthase complex