Green - Pentose Phosphate Pathway

Question 1

Two Major Products of Pentose Phosphate Pathway?

Role of Glutathione?

Answer 1

1. Produces NADPH
   - Required for Fatty Acid Synthesis
   - Required for synthesis of cholesterol and steroid hormones
   - Regenerates reduced glutathione to counter damage from oxygen radicals
2. Produces Robose 5-Phosphate
   - Required for DNA, RNA, NADH, FADH₂ and CoA

Glutathione counters damage from oxygen radicals!

Question 2

Two Major Phases of P.P. Pathway?

Answer 2

Oxidative Phase ( making NADPH )

Non-Oxidative Phase ( not making NADPH )

Question 3

Key regulatory enzyme of Oxidative Phase of PP Pathway?

Regulation?

Answer 3

Glucose 6-Phosphate Dehydrogenase (G6PD)

Inhibit: High NADPH

Activate: Low NADPH

• Product based feedback

Question 4

Major enzymes for Non-Oxidative Phase

What type of cofactor do these require?

Answer 4

Epimerase, Transketolase, Transaldolase, Transketolase

EP, TK, TA, TK

TK’s require TPP (Thiamine or B₁) as cofactor

Question 5

Carbon counting in the Non-Oxidative phase?

Answer 5

Start: Six, 5-carbon sugar phosphates

End: Five, 6-carbon sugar phosphates

6,5 to 5,6

Question 6

Wenicke-Korsakoff Syndrome

Answer 6

Severe thiamine deficiency

• Memory loss, confusion, vision issues, paralysis
• Mutation can lower affinity of transketolase gene to TPP
• Pentose phosphate pathway shuts down

Question 7

What is the fate of Glyceraldehyde 3-Phosphate?

Answer 7

Can enter glycolytic or gluconeogenic pathways

Question 8

How is PP Pathway regulated?

Answer 8

A. Regulation Based on Cellular Demand (4 scenarios)

1. High Demand for Ribose
2. High Demand for Ribose + NADPH
3. High Demand for NADPH
4. High Demand for Energy + NADPH

B. Regulation Based on NADPH

- Negative Feedback at Glucose 6-Phosphate junction point

Question 9

Glutathione role in protection of cells

What does regeneration of reduced glutathione require?

Answer 9

Glutathione protects cells against reactive oxygen species

Sources of radicals: Mitochondrial respiration, ionizing radiation, sulfa drugs, herbicides, antimalarials, divicine

Regeneration of reduced glutathione requires NADPH

Question 10

Glucose 6-Phosphate Dehydrogenase (G6PD) Deficiency

Answer 10

• 400,000 worldwide, most common in Africa

1/10 African American males have defective gene

X Linked

Presentation:

• Stress from infection, certain drugs, herbicides, divicine from fava beans
• Results in inability to generate NADPH to be used in regeneration of reduced glutathione

- Hemolytic anemia

Question 11

Main goal of non-oxidative phase?

Answer 11

Convert six 5-carbon sugars to five 6-carbon sugars