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.
G 6-P
NADP
6-phospho- glucono-d-lactone
Glucose 6-phosphate dehydrogenase
NADPH
72. Conversion of 6-phosphoglucono-d-lactone to
6-phosphogluconate
6-phospho- glucono-d-lactone
- Lactonase hydrolyzes 6-phosphoglucono-d-lactone,
producing 6-phosphogluconate.
H2O
6-phospho- gluconate
lactonase
83. Oxidation and decarboxylation of
6-phosphogluconate
- Oxidation and decarboxylation of
6-phosphogluconate is catalyzed by
6-phosphogluconate dehydrogenase. This reaction
also produces NADPH.
6-phosphogluconate
NADP
D-ribulose 5-phosphate
6-phosphogluconate dehydrogenase
NADPH
CO2
94. Conversion of ribulose 5-phosphate to ribose
5-phosphate
D-ribulose 5-phosphate
- Ribulose 5-phosphate is converted to ribose
5-phosphate by phosphopentose isomerase. - In some tissues, the PPP ends at this point.
D-ribose 5-phosphate
Phosphopentose isomerase
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.
Ribose 5-phosphate epimerase
CH2OH
I
CO
I
H-
-OH
-H
OH -
C
I
H-C-OH
I
CH2OPO32-
Ribulose 5-phosphate
Xylulose 5-phosphate
13Transketolase and transaldolase rearrange the
carbon skeleton, producing 5 fructose 6-phosphate
from 6 ribose 5-phosphate
Sedoheptulose 7-phosphate
Fructose 6-phosphate
Ribose 5-phosphate
Ribose 5-phosphate
G 6-P
G 6-P
G 6-P
G 6-P
Phosphohexose isomerase
Phosphohexose isomerase
Erythrose 4-phosphate
Fructose 6-phosphate
Sedoheptulose 7-phosphate
Xylulose 5-phosphate
G 3-P
transaldolase
epimerase
transketolase
Erythrose 4-phosphate
F 6-P
F 6-P
Xylulose 5-phosphate
G 3-P
?FBPase-1 ?Aldolase ?Triose phosphate isomerase
F 6-P
G 3-P
transketolase
F 6-P
Xylulose 5-phosphate
G 3-P
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. - Both enzymes catalyze similar reaction.
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
Glucose
- NADP stimulate G6PD. When NADP is high
(meaning more NADPH is consumed), G6PD is
stimulated and G-6-P is flowing toward PPP.
G 6-P
G 6-P
glycolysis
ATP
G6PD
G6PD
NADPH
NADPH
6-phospho- gluconate
6-phospho- gluconate
NADPH
NADPH
Pentose phosphates
Pentose phosphates
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.
19O2
Mitochondrial respiration, ionizing radiation,
sulfa drugs, herbicides, antimalarials, divicine
?O2-
?O2-
Superoxide radical
2H
e-
H2O2
H2O2
H2O
Hydrogen peroxide
Glucose 6-phosphate dehydrogenase
NADPH
NADP
NADPH
6-phospho-glucono-d-lactone
G6P
20O2
Mitochondrial respiration, ionizing radiation,
sulfa drugs, herbicides, antimalarials, divicine
?O2-
?O2-
Superoxide radical
2H
e-
H2O2
H2O2
H2O2
H2O
H2O2
Hydrogen peroxide
H
e-
H2O
? OH
Hydroxyl free radical
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