MCBG Session 6 - Catabolic Pathways (Part 2)

Question 1

What is the pentose phosphate pathway & when does it occur?

Answer 1

• When intermediates of glycolysis are high (e.g.: G6P after 1st reaction) - they are diverted into different pathways - e.g.: pentose phosphate pathways.

Question 2

What are the 2 steps + products of the pentose phosphate pathway?

Answer 2

1) Oxidative phosphorylation - G6P to 5C sugar + CO2 (NADPH produced!)
2) 3 x 5C sugars into 2x fructose 6P & Glyceraldehyde 6P

Question 3

What are the main features of the PP pathway?

Answer 3

1) No ATP production
2) Loss of CO2, therefore irreversible
3) Controlled by NADP+/NADPH ratio at G6P DH

Question 4

What are the main functions of the PP pathway?

Answer 4

1) Produce NADPH in cytoplasm for biosynthetic reducing power & to maintain free SH groups on certain protein.
2) Produce 5C sugars needed for nucleic acid synthesis.

Question 5

What is the consequence of G6P deficiency?

Answer 5

• Reduced G6P levels = less pentose phosphate pathway can occur - therefore a reduction in NADPH –> disulphide bonds formed –> proteins aggregate –> heinz bodies –> haemolysis
• Ultimately causes functioning deficiencies in proteins, e.g.: RBC’s and lens of the eye.

Question 6

What is meant by allostery (allosteric regulation) and covalent modification ((de)phosphorylation)?

Answer 6

Allostery = binding of molecules to site other than active site (can be stimulatory or inhibitory)
Covalent modification = introduction of bulky negatively charged PO4^2- moiety which alters protein structure and activity

Question 7

Which steps in metabolic pathways are regulated?

Answer 7

• Irreversible steps

- Reverisble can be regulated to a point, i.e.: the equilibrium can be pushed to one side by adding more of one product.

Question 8

What is feedback/product inhibition?

Answer 8

When a product inhibits an earlier step in the metabolic pathway.

NB: Often allosteric inhibition occurs on the first enzyme in the pathway via feedback inhibition.

Question 9

What is meant by the committing step?

Answer 9

The step at which, if completed, the pathway must continue to completion (inhibition of this step allows substrate to be diverted into other pathways).

Question 10

What are catabolic pathways inhibited and activated by?

Answer 10

Inhibited by - High energy signals (ATP, NADH, FADH2)

Stimulated by - Low energy signals (ADP, AMP, NAD+)

Question 11

How does hormonal regulation of metabolic pathways work?

Answer 11

• Hormone binds to receptor
• Protein kinase (phosphorylation) or protein phosphatase (dephosphorylation) activated
• Alters protein conformation and activity depending on target enzyme

Question 12

What are the 3 enzymes in glycolysis that can be regulated? - Which one is the key regulatory enzyme?

Answer 12

• Hexokinase
• Phosphofructokinase-1 (PFK-1) - Key enzyme
• Pyruvate Kinase

Question 13

What are the 3 enzymes (including PFK-1) in glycolysis regulated by (both metabolic and hormonal)

Answer 13

Metabolic =

• high NADH (inhibits at step 6)
• high ATP inhibits PFK
• High AMP stimulates PFK

Hormonal =

• Insulin (stimulates PFK + pyruvate kinase via dephosphorylation of protein phosphatase 1)
• Glucagon (inhibits PFK + pyruvate kinase via phosphorylation of protein kinase A).