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Pentose phosphate pathway

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).

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Pentose phosphate pathway

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  1. Pentose phosphate pathway Pentose phosphate pathway has two phases

  2. 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).

  3. 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.

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

  5. The oxidative phase of PPP Products of this phase are ribose 5-phosphate and NADPH

  6. 1. Glucose 6-phosphate dehydrogenase (G6PD) produces NADPH and 6-phosphoglucono-d-lactone • G6PD oxidize glucose 6-phosphate, producing NADPH and 6-phosphoglucono-d-lactone. • Deficiency of G6PD causes favism.

  7. 2. Conversion of 6-phosphoglucono-d-lactone to 6-phosphogluconate • Lactonase hydrolyzes 6-phosphoglucono-d-lactone, producing 6-phosphogluconate.

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

  9. 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.

  10. The nonoxidative phase of PPP Nonoxidative phase of PPP is very important for tissues that only require NADPH but not ribose 5-phosphate

  11. 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.

  12. 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.

  13. Transketolase and transaldolase rearrange the carbon skeleton, producing 5 fructose 6-phosphate from 6 ribose 5-phosphate

  14. 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.

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

  16. Nonoxidative phase of PPP provides a means of converting hexose phosphates 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.

  17. 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.

  18. 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.

  19. Decreased [NADPH]  Favism

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