Pentose phosphate pathway

Pentose phosphate pathway has two phases

The main product of PPP is ribose 5-phosphate and NADPH

• PPP oxidizes glucose 6-phosphate, producing ribose 5-phosphate (precursor for nucleotides) and NADPH (reducing agent for lipid biosynthesis).

What type of tissues require PPP?

• Rapid dividing cells (bone marrow, skin, intestinal mucosa….)

• Tissues that carry out extensive fatty acid synthesis (liver, adipose, lactating mammary gland) or very active synthesis of cholesterol and steroid hormones (liver, adrenal glands, gonads).

• Erythrocytes, lens and cornea cells.

PPP is highly active in fatty acid- and steroid- synthesizing tissues

The oxidative phase of PPP

Products of this phase are ribose 5-phosphate and NADPH

1. Glucose 6-phosphate dehydrogenase (G6PD) produces NADPH and 6-phosph

oglucono--lactone

• G6PD oxidize glucose 6-phosphate, producing NADPH and 6-phosphoglucono--lactone.

• Deficiency of G6PD causes favism.

2. Conversion of 6-phosphoglucono--lactone to 6-phosphogluconate

• Lactonase hydrolyzes 6-phosphoglucono--lactone, producing 6-phosphogluconate.

3. Oxidation and decarboxylation of 6-phosphogluconate

• Oxidation and decarboxylation of 6-phosphogluconate is catalyzed by 6-phosphogluconate dehydrogenase. This reaction also produces NADPH.

4. Conversion of ribulose 5-phosphate to ribose 5-phosphate

• Ribulose 5-phosphate is converted to ribose 5-phosphate by phosphopentose isomerase.

• In some tissues, the PPP ends at this point.

The nonoxidative phase of PPP

Nonoxidative phase of PPP is very important for tissues that only require N

ADPH but not ribose 5-phosphate

Nonoxidative phase is important for recycling ribose 5-phosphate

• For cells carrying out extensive fatty acid, cholesterol, or steroid hormone synthesis, only NADPH is required from PPP but not ribose 5-phosphate.

• In addition, erythrocytes, lens and cornea cells also do not need ribose 5-phosphate.

• In these tissues, ribose 5-phosphate produced by PPP must be recycled.

Nonoxidative phase starts with epimerization of ribulose 5-phosphate

• Ribulose 5-phosphate is epimerized to xylulose 5-phosphate by ribose 5-phosphate epimerase, which starts the nonoxidative phase of PPP.

Transketolase and transaldolase rearrange the carbon skeleton, producing 5 fructose 6-phosp

hate from 6 ribose 5-phosphate

Transketolase

• Transketolase catalyzes the transfer of a two-carbon fragment from a ketose donor to an aldose acceptor.

• Transketolase need the coenzyme TPP. A mutation resulting in 1/10 affinity for TPP causes genetic disorder Wernicke-Korsakoff syndrome (p. 554): severe memory loss, mental confusion, and partial paralysis.

Transaldolase

• Transaldolase cleaves the ketose and transfer one of the fragment to a aldose.

Nonoxidative phase of PPP provides a means of converting hexose phosp

hates to pentose phosphates

• Nonoxidative phase of PPP is reversible and happens in cytosol.

• During photosynthetic assimilation of CO2, nonoxidative phase of PPP is very important in converting hexose phosphates to pentose phosphates.

Glucose 6-phosphate is partitioned between glycolysis and PPP by

[NADP+]

• NADP+ stimulate G6PD. When [NADP+] is high (meaning more NADPH is consumed), G6PD is stimulated and G-6-P is flowing toward PPP.

Favism is a deficiency of G6PD

• Deficiency of G6PD block the first step of PPP.

• However, because cells have other pathway to synthesize ribose 5-phosphate, G6PD deficiency is generally nonfatal and asymptomatic.

Decreased [NADPH] Favism