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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). - PowerPoint PPT Presentation
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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.
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.
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.