Protein control: (leyland) carb metabolism 3

Question 1

What is the purpose of the pentose-phosphate pathway (PPP) and what are the main locations where this occurs?

Answer 1

1) Oxidation of G6P to eventually form Ribose 5-phosphate (5C sugars)
2) Formation of NADPH

High PPP activity in:
Liver
Red blood cells
Adipose tissue

Question 2

Key stage/enzyme of regulation in PPP?

Answer 2

Glucose 6-phosphate dehydrogenase

Converts G6P to 6-Phosphogluconate , NADP+ to NADPH

Question 3

What does G6PDH (G6P dehydrogenase) deficiency cause and why?

Answer 3

Causes haemolytic anaemia

Reactive oxygen species damage membranes

Low levels of glutathione -> cannot reduce disulphide bonds, leads to:

• Cross-linking of Hb
• formation of Heinz bodies
• Lysing of red blood cells

Question 4

Describe glycogen molecule

Answer 4

Polysaccharide of glucose molecules

• alpha-1,4 linkages
• alpha-1,6 linkages form branch points

Question 5

Key enzymes involved in glycogenesis and glycogenolysis

Answer 5

Synthesis: Glycogen synthase

Degradation: Glycogen phosphorylase

Question 6

Which molecule links glycogen synthesis/degradation pathway to G6P? How is it formed?

Answer 6

Glucose 1P

G6P coverted to G1P (by phosphoglucomutase)

Question 7

Which tissues are the main storages of glycogen?

Answer 7

liver: maintain blood glucose conc.

skeletal muscle: G6P production to allow ATP synthesis for energy in muscle contraction

Question 8

How is glycogen phosphorylation (degradation) regulated?

Answer 8

G-protein coupled receptors (glucagon in liver, adrenaline in muscle) -> PKA

PKA phosphorylates intermediate which then phosphorylates glycogen phosphorylase

Phosphorylation of glycogen phosphorylase (intermediate) converts it from low activity to high activity form (phosphorylase b -> phosphorylase a)

Question 9

Different allosteric regulators in skeletal muscle and liver tissue?

Answer 9

Allosteric modulators different due to different isozymes in muscle + liver

Liver
- - Glucose

Muscle
++ AMP, Ca2+
- - ATP, G6P

Question 10

How is glycogen synthase reciprocally inhibited by an increase in glycogenolysis activity?

Answer 10

Same signalling mechanism which increases glycogenphosphatase also reciprocally inhibits glycogen synthase

GPCR -> cAMP -> PKA

PKA converts glycogen synthase a (high activity form) to glycogen synthase b (low activity form)

Question 11

Function of glycogen synthase kinase-3? How is it inhibited?

Answer 11

Phosphorylates and deactivates glycogen synthase

inhibited when phosphorylated (by PKB)

Question 12

2 ways PKA inhibits phosphatase activity in the cell during fasted state / glycogenolysis

Answer 12

1) PKA phosphorylates glycogen targeting protein -> prevents PP1 from associating with glycogen, meaning it is not physically close to reactions -> reduced activity
2) PKA phosphorylates and activates PP1-inhibitor molecule -> binds tightly to PP1 and inactivates it

Question 13

Describe insulin induced pathway of stimulated glycogen synthesis

Answer 13

Insulin binds to TK receptor

• activates Protein Kinase B (PKB)
• leads to phosphorylation + DEactivation of glycogen synthase kinase-3 (GSK3)
• > GSK3 inactive so cannot phosphorylate and deactive glycogen synthase a
• > increased GS activity and glycogen synthesis

Question 14

How does PP1 become more active in the fed state? What does this result in?

Answer 14

Glucose binds to to Glycogen Phosphorylase (GP) -> exposes phosphoserines

Insulin-stimulated activation of PP1 causes dephosphorylation of GP

-> T state form now stabilised -> lower activity

PP1 dephosphorylates Glycogen synthase (GS) -> higher activity

Question 15

General process which increases enzyme activity in glycogenesis

Answer 15

Dephosphorylation

Question 16

General process which increases enzyme activity in glycogenolysis

Answer 16

Phosphorylation