Title: Pentose phosphate pathway
1Pentose phosphate pathway
- Pentose phosphate pathway has two phases
2The 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).
3What 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.
4PPP is highly active in fatty acid- and steroid-
synthesizing tissues
5The oxidative phase of PPP
- Products of this phase are ribose 5-phosphate and
NADPH
61. 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.
72. Conversion of 6-phosphoglucono-d-lactone to
6-phosphogluconate
- Lactonase hydrolyzes 6-phosphoglucono-d-lactone,
producing 6-phosphogluconate.
83. Oxidation and decarboxylation of
6-phosphogluconate
- Oxidation and decarboxylation of
6-phosphogluconate is catalyzed by
6-phosphogluconate dehydrogenase. This reaction
also produces NADPH.
94. 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.
10The nonoxidative phase of PPP
- Nonoxidative phase of PPP is very important for
tissues that only require NADPH but not ribose
5-phosphate
11Nonoxidative 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.
12Nonoxidative 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.
13Transketolase and transaldolase rearrange the
carbon skeleton, producing 5 fructose 6-phosphate
from 6 ribose 5-phosphate
14Transketolase
- 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.
15Transaldolase
- Transaldolase cleaves the ketose and transfer one
of the fragment to a aldose.
16Nonoxidative 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.
17Glucose 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.
18Favism 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.
19Decreased NADPH ? Favism
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