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Pentose phosphate pathway
Prepared by
Maria Gul
The pentose phosphate pathway is also called as
• hexose monophosphate pathway
• 6-phosphogluconate pathway
• Hexose Monophosphate Shunt
• IRREVERSIBLE Oxidative Phase Generates NADPH
Dehydrogenation of glucose 6-phosphate to 6-
phosphogluconate occurs via the formation of 6-
phosphogluconolactone catalyzed by glucose 6-phosphate
dehydrogenase, an NADPdependent enzyme (The hydrolysis of
6-phosphogluconolactone is accomplished by the enzyme
gluconolactone hydrolase.
• A second oxidative step is catalyzed by 6-phosphogluconate
dehydrogenase, which also requires NADP+ as hydrogen
acceptor. Decarboxylation follows with the formation of the
ketopentose ribulose 5-phosphate.
1. glucose 6-phosphate dehydrogenase
2. gluconolactone hydrolase
• occurs in the cytosol of the cell. It includes two
irreversible oxidative reactions, followed by a series of
reversible sugar–phosphate interconversions.
• No ATP is directly consumed or produced in the cycle.
• ribose 5-phosphate, required for the biosynthesis of
nucleotides
• Glucose-6-phosphate Dehydrogenase catalyzes
oxidation at C1 of glucose-6-phosphate, to a carboxylic
acid, in ester linkage (lactone).
• NADP+ serves as electron acceptor
 The pentose phosphate pathway is regulated primarily
at the G6PD reaction. NADPH is a potent competitive
inhibitor of the enzyme and, under most metabolic
conditions, the ratio of NADPH/NADP+ is sufficiently
high to substantially inhibit enzyme activity.
 However, with increased demand for NADPH, the ratio
of NADPH/NADP+ decreases and flux through the
cycle increases in response to the enhanced activity of
G6PD.
B. Formation of ribulose 5-phosphate
6-phosphogluconate undergo oxidative
decarboxylation by 6-phosphogluconate
dehydrogenase. This irreversible reaction
produces a pentose sugar–phosphate
(ribulose 5-phosphate), CO2 (from carbon 1 of
glucose), and a second molecule of NADPH.
2. REVERSIBLE NONOXIDATIVE REACTIONS
The nonoxidative reactions of the pentose
phosphate pathway occur in all cell types
synthesizing nucleotides and nucleic acids.
These reactions catalyze the interconversion of
sugars containing three to seven carbons. These
reversible reactions permit ribulose 5-phosphate
(produced by the oxidative portion of the
pathway) to be converted either to ribose 5-
phosphate (needed for nucleotide synthesis or to
intermediates of glycolysis—fructose 6-
phosphate and glyceraldehyde 3-phosphate.
• For example, many cells that carry out reductive
biosynthetic reactions have a greater need for
NADPH than for ribose 5-phosphate. In this case,
transketolase and transaldolase convert the
ribulose 5-phosphate produced as an endproduct
of the oxidative reactions to glyceraldehyde 3-
phosphate and fructose 6-phosphate, which are
intermediates of glycolysis.
• the nonoxidative reactions can provide the
biosynthesis of ribose 5-phosphate from
glyceraldehyde 3-phosphate and fructose 6-
phosphate in the absence of the oxidative steps.
Importance
• Ribose 5 phosphate
• NADPH required in different cycles
• g6pd
Importance of HMP shunt
In red blood cells the pentose phosphate pathway provides NADPH for the
reduction of oxidized glutathione catalyzed
by glutathione reductase, a flavoprotein containing FAD. Reduced
Reduced glutathione removes H2O2 in a reaction catalyzed by glutathione
peroxidase, an enzyme that contains the selenium analogue of cysteine
(selenocysteine) at the active site (Figure 21–3). The reaction is important,
since accumulation of H2O2 may decrease the life span of the erythrocyte by
causing oxidative damage to the cell membrane, leading to hemolysis
Lec 57
Lec 57

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Lec 57

  • 2. The pentose phosphate pathway is also called as • hexose monophosphate pathway • 6-phosphogluconate pathway • Hexose Monophosphate Shunt • IRREVERSIBLE Oxidative Phase Generates NADPH Dehydrogenation of glucose 6-phosphate to 6- phosphogluconate occurs via the formation of 6- phosphogluconolactone catalyzed by glucose 6-phosphate dehydrogenase, an NADPdependent enzyme (The hydrolysis of 6-phosphogluconolactone is accomplished by the enzyme gluconolactone hydrolase. • A second oxidative step is catalyzed by 6-phosphogluconate dehydrogenase, which also requires NADP+ as hydrogen acceptor. Decarboxylation follows with the formation of the ketopentose ribulose 5-phosphate.
  • 3. 1. glucose 6-phosphate dehydrogenase 2. gluconolactone hydrolase
  • 4. • occurs in the cytosol of the cell. It includes two irreversible oxidative reactions, followed by a series of reversible sugar–phosphate interconversions. • No ATP is directly consumed or produced in the cycle. • ribose 5-phosphate, required for the biosynthesis of nucleotides • Glucose-6-phosphate Dehydrogenase catalyzes oxidation at C1 of glucose-6-phosphate, to a carboxylic acid, in ester linkage (lactone). • NADP+ serves as electron acceptor
  • 5.  The pentose phosphate pathway is regulated primarily at the G6PD reaction. NADPH is a potent competitive inhibitor of the enzyme and, under most metabolic conditions, the ratio of NADPH/NADP+ is sufficiently high to substantially inhibit enzyme activity.  However, with increased demand for NADPH, the ratio of NADPH/NADP+ decreases and flux through the cycle increases in response to the enhanced activity of G6PD.
  • 6. B. Formation of ribulose 5-phosphate 6-phosphogluconate undergo oxidative decarboxylation by 6-phosphogluconate dehydrogenase. This irreversible reaction produces a pentose sugar–phosphate (ribulose 5-phosphate), CO2 (from carbon 1 of glucose), and a second molecule of NADPH.
  • 7. 2. REVERSIBLE NONOXIDATIVE REACTIONS The nonoxidative reactions of the pentose phosphate pathway occur in all cell types synthesizing nucleotides and nucleic acids. These reactions catalyze the interconversion of sugars containing three to seven carbons. These reversible reactions permit ribulose 5-phosphate (produced by the oxidative portion of the pathway) to be converted either to ribose 5- phosphate (needed for nucleotide synthesis or to intermediates of glycolysis—fructose 6- phosphate and glyceraldehyde 3-phosphate.
  • 8. • For example, many cells that carry out reductive biosynthetic reactions have a greater need for NADPH than for ribose 5-phosphate. In this case, transketolase and transaldolase convert the ribulose 5-phosphate produced as an endproduct of the oxidative reactions to glyceraldehyde 3- phosphate and fructose 6-phosphate, which are intermediates of glycolysis. • the nonoxidative reactions can provide the biosynthesis of ribose 5-phosphate from glyceraldehyde 3-phosphate and fructose 6- phosphate in the absence of the oxidative steps.
  • 9.
  • 10.
  • 11. Importance • Ribose 5 phosphate • NADPH required in different cycles • g6pd
  • 12. Importance of HMP shunt In red blood cells the pentose phosphate pathway provides NADPH for the reduction of oxidized glutathione catalyzed by glutathione reductase, a flavoprotein containing FAD. Reduced Reduced glutathione removes H2O2 in a reaction catalyzed by glutathione peroxidase, an enzyme that contains the selenium analogue of cysteine (selenocysteine) at the active site (Figure 21–3). The reaction is important, since accumulation of H2O2 may decrease the life span of the erythrocyte by causing oxidative damage to the cell membrane, leading to hemolysis