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- phosphoglucono-  -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 NADPH 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- phosphate 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 phosphates to pentose phosphates Nonoxidative phase of PPP is reversible and happens in cytosol. During photosynthetic assimilation of CO 2, 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