Pentose phosphate pathway

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Pentose phosphate pathway

• Pentose phosphate pathway has two phases

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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).

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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.

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PPP is highly active in fatty acid- and steroid-
synthesizing tissues
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The oxidative phase of PPP

• Products of this phase are ribose 5-phosphate and
  NADPH

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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.

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

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

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3. Oxidation and decarboxylation of
6-phosphogluconate

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

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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.

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The nonoxidative phase of PPP

• Nonoxidative phase of PPP is very important for
  tissues that only require NADPH but not ribose
  5-phosphate

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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.

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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.

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

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Transaldolase

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

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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.

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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.

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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.

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Decreased NADPH ? Favism
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