6 - Pentose Phosphate Pathway or Hexose Monophosphate Shunt

1 - What is the first step of the oxidative phase of PPP?

Glucose-6-phosphate is oxidized to 6-phosphoglucono-δ-lactone by glucose-6-phosphate dehydrogenase (G6PD), producing NADPH.

2 - What is the second step of the oxidative phase?

6-phosphoglucono-δ-lactone is hydrolyzed to 6-phosphogluconate by lactonase.

3 - What is the third step of the oxidative phase?

6-phosphogluconate is oxidatively decarboxylated by 6-phosphogluconate dehydrogenase to form ribulose-5-phosphate, releasing CO₂ and producing a second NADPH.

1 - What is the first reaction of the non-oxidative phase?

Ribulose-5-phosphate is isomerized to ribose-5-phosphate by phosphopentose isomerase.

2 - What is the function of ribose-5-phosphate in the PPP?

It is used for nucleotide and nucleic acid synthesis.

3 - What happens to excess ribose-5-phosphate in cells not actively synthesizing nucleotides?

It is converted into glycolytic intermediates (fructose-6-phosphate and glyceraldehyde-3-phosphate) via transketolase and transaldolase.

4 - What is the function of transketolase in the non-oxidative phase?

Transfers a 2-carbon unit from a ketose donor to an aldose acceptor, helping interconvert sugars.

5 - What coenzyme is required by transketolase?

Thiamine pyrophosphate (TPP).

6 -What is the function of transaldolase in the PPP?

Transfers a 3-carbon unit between sugar phosphates, allowing formation of fructose-6-phosphate and glyceraldehyde-3-phosphate.

Name the important products of the Pentose Phosphate Pathway.

1. NADPH

2. Ribose - 5 - phosphate

3. Glycolytic intermediates (from recovery phase)

For what purpose are these products produced?

• It oxidizes glucose-6-phosphate (glucose) to generate NADPH for reductive biosynthetic reactions

• It generates RIBOSE -5-PHOSPHATE for nucleotide biosynthesis

• It is used to convert (excess) PENTOSES into HEXOSES. These “new” hexoses can then enter the other pathways of carbohydrate metabolism

Why are these metabolic products important?

• Generate 12 NADPH from the complete oxidation of one glucose molecule by using the oxidative phase and the complete recovery phase. {6 glucose-6-phosphate → 5 glucose-6-phosphate + 6 CO

• Generate 2 NADPH and 1 ribose-5-phosphate from 1 glucose-6-phosphate by using the oxidative phase and part of the recovery phase.

• Convert excess pentoses into hexoses by utilizing the recovery phase.

• Generate ribose-5-phosphate by utilizing the recovery phase in reverse

Discuss the amount of products formed

1. 12 NADPH – used for biosynthetic reactions, antioxidant defense, immune function

2. 6 ribulose-5-phosphate – cancel out

3. 6 CO2

What is the importance of NADPH?

is essential for:

• Reductive biosynthesis (e.g., fatty acid and cholesterol synthesis)

• Maintaining reduced glutathione for protection against oxidative damage

What is the importance of Ribose-5-phosphate?

used for nucleotide and nucleic acid synthesis

Discuss the control points of the oxidative phase of the Pentose Pathway.

Glucose-6-phosphate dehydrogenase (G6PD) is the committed step!!

Describe the allosteric effectors and how they affect the enzymes.

Allosteric activation: NAD+ stimulates G6PD

Allosteric inhibition: NADPH inhibits G6PD

Discuss the importance of the recovery (regeneration) phase of the pathway.

Purpose is to convert unused ribose–phosphate back into glycosidic intermediates: fructose-6-phosphate and glyceraldehyde-3-phosphate (G3P)

What is the biochemical importance of the products?

• Reuse carbons for energy production (via glycolysis)

• Recycle them for gluconeogenesis

• Adjust the balance between NADPH production and nucleotide biosynthesis