Glycogen Metabolism

C483 Spring 2013

1. Why does glycolysis produce more energy (more ATP) from glucose units released by glycogen degradation than from free glucose?A) Limit dextrin contains additional molecules.B) The debranching enzyme releases free glucose.C) The glucose is already phosphorylated after glycogen phosphorylase action.D) The glucose from glycogen degradation bypasses glycolysis.E) All of the above.

2. What is the driving force for the reaction catalyzed by UDP-glucose pyrophosphorylase that converts glucose 1-phosphate to UDP-glucose?A) The subsequent hydrolysis of pyrophosphate.B) The formation of an energy-rich product.C) Its large negative free energy change. D) The change in concentration of UTP.

3. Glycogen phosphorylase is ________ (more, less) active when not phosphorylated, and it is ________ (activated, inhibited) by glucose 6-phosphate. A) more; activated B) less; activated C) more; inhibited D) less; inhibited

Glucose Metabolism Overview

• Keep the main pathway purposes distinct

• But learn details of chemistry and regulation based on similarities

OHO

HO

OH (P)

OH

OH

DHAP

Pyruvate

Gluconeogenesis

Lactate

Amino Acids

Glycerol(Triacylglycerides)

Glycogen

Glycogen Degradation

Glycogen

Glycogen Synthesis

Ribose,NADPH

ATP

DHAP

Pyruvate

Pentose Phosphate Pathway

Energy Production

Starch

Diet

Glycogen

• Storage molecule• Primer necessary• Very large!• Multiple ends allow

for quick synthesis and degradation

Chemistry of Synthesis

• Step 1

• Near equilibrium• The link to glucose-6-phophate, our central

molecule

O

H

HO

H

HO

H

OH

OHHH

OP

O

H

HO

H

HO

H

O

OHHH

OH

PO3-2Glucose-6-phosphate glucose-1-phophate

Chemistry of Synthesis• Step 2

• Count high energy bonds• Pyrophosphatase• UDP-glucose: activated for incorporation

OHO

HO

O

OH

OH

NH

O

ONO

OHOH

OPOO

OPO

OOP

O

OO

P

O

O O

OHPO

OOP

O

OO 2 Pi

OHO

HO

O

OH

OH

NH

O

ONO

OHOH

OPOO

OPO

O

Chemistry of Synthesis• Step 3

• Growing end is non-reducing• UDP released

Energetics of Synthesis

• Total cost: one ATP equivalent

OHO

HO

O

OH

OH

P

O

O O

OHO

HO

O

OH

OH

P-P-Uridine

OHO

OH

OH

OH

O

O

OH

HO

O

HO

Glucose-6-PUDP

UTP

2 Pi

Chemistry of Degradation

• Inorganic phosphate as a nucleophile

Overall Energetics

OHO

HO

O

OH

OH

P

O

O O

OHO

HO

O

OH

OH

P-P-Uridine

OHO

OH

OH

OH

O

O

OH

HO

O

HO

Glucose-6-PUDP

UTP

2 Pi

Pi

Key Enzymes

OHO

HO

O

OH

OH

P

O

O O

OHO

HO

O

OH

OH

P-P-Uridine

OHO

OH

OH

OH

O

O

OH

HO

O

HO

Glucose-6-PUDP

UTP

2 Pi

Pi

Glycogen Synthase

Glycogen Phosphorylase

Regulation of Glycogen Phosphorylase b

• Prototype of Allosteric regulation

• Happens in muscle exertion

Hormone Regulation

• Glucagon• Signal Transduction• Covalent Modification• Glycogen phosphorylase b becomes glycogen

phosphorylase a

Regulation of Glycogen Phosphorylase a

• Relaxed state now favored

• No allosteric effects except glucose deactivation in the liver

Glucagon and Insulin

• Act Reciprocally on Glycogen synthase and Glycogen phosphorylase

Maintenance of Blood Sugar

Answers

1. C2. A3. D