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Also called the pentose phosphate pathway, or phosphogluconate pathway It consists of two irreversible oxidative reactions, followed by a series of reversible sugar-phosphate interconversions No ATP is directly consumed or produced in the cycle. Carbon 1 of glucose 6-phosphate is released as CO2, and two NADPH are produced for each glucose 6-phosphate entering the oxidative part of the pathway. The rate and direction of the reactions at any given time are determined by the supply of and demand for intermediates in the cycle. The HMP occurs in the cytosol of the cell. The pathway provides a major portion of the cell's NADPH, which functions as a biochemical reductant. Hexose Monophosphate Pathway

Also called the pentose phosphate pathway, or phosphogluconate pathway It consists of two irreversible oxidative reactions, followed by a series of

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Page 1: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

Also called the pentose phosphate pathway, or phosphogluconate

pathway

It consists of two irreversible oxidative reactions, followed by a series

of reversible sugar-phosphate interconversions

No ATP is directly consumed or produced in the cycle.

Carbon 1 of glucose 6-phosphate is released as CO2, and two NADPH

are produced for each glucose 6-phosphate entering the oxidative part

of the pathway.

The rate and direction of the reactions at any given time are

determined by the supply of and demand for intermediates in the cycle.

The HMP occurs in the cytosol of the cell.

The pathway provides a major portion of the cell's NADPH, which

functions as a biochemical reductant.

The HMP also produces ribose-phosphate, required for biosynthesis of

nucleotides,

Hexose Monophosphate Pathway

Page 2: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

Hexose Monophosphate Pathway

Page 3: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

The oxidative portion of the HMP leads to the formation of

ribulose 5-phosphate, CO2, and two molecules of NADPH

for each molecule of glucose 6-phosphate oxidized.

A. Dehydrogenation of glucose 6-phosphate

B. Hydrolysis of 6-phosphogluconolactone and formation of

ribulose 5-phosphate.

Oxidative Reactions

Reductive anabolic pathway

NADPH

NADP+

H+

NADPH

NADP+

G6PO46-Phospho

gluconate Ribulose-5-PO4 Xylulose5

phosphate 1 2

Oxidative Reaction Irreversible

Page 4: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

Glucose-6-phosphate Dehydrogenase catalyzes oxidation

of the aldehyde at C1 of glucose-6-phosphate, to a

carboxylic acid in ester linkage (lactone). NADP+ serves as electron acceptor. Lactone is hydrolyzed resulting in ring opening. The

product is 6-phosphogluconate.

Oxidative Reactions

Page 5: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

Phosphogluconate Dehydrogenase catalyzes oxidative

decarboxylation of 6-phosphogluconate, to yield the 5-C ketose

ribulose-5-phosphate. NADP+ again serves as oxidant (electron acceptor).Regulation: Glucose-6-phosphate Dehydrogenase is the

committed step of the Pentose Phosphate Pathway. This enzyme is

regulated by availability of the substrate NADP+. As NADPH is utilized

in reductive synthetic pathways, the increasing concentration of

NADP+ stimulates the Pentose Phosphate Pathway, to replenish

NADPH.

Oxidative Reactions

Structure of NADPHStructure of NADPH

Page 6: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

Hexose Monophosphate PathwayNonoxidative reaction

Transketolase (transfer 2-C unit) and Transaldolase (transfer 3-C unit)

Ribose-5-PO4Sedoheptulose

–7-PO4

Nucleic acid biosynthesis

Erythrose-4-PO4

Xylulose-5-PO4

Ribulose-5-PO4

Xylulose-5-phosphate

Glyceraldehyde-3-PO4

Fructose-6-PO4

Fructose-6-PO4 Glyceraldehydes

-3-PO4

Glycolic pathway

Page 7: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

Formation of ribose 5-

phosphate from

intermediates of

glycolysis Under conditions where

the demand for pentoses

for incorporation into

nucleotides and nucleic

acids is greater than the

need for NADPH, the

nonoxidative reactions can

provide the biosynthesis of

ribose 5-phosphate from

fructose 6-phosphate in

the absence of the

oxidative steps.

Nonoxidative reactions

Page 8: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

Uses of NADPH

Structure of NADPHStructure of NADPH

Reductive biosynthesis:

The electrons in NADPH are destined for use in reductive

biosynthesis rather than for transfer to oxygen as in the case

with NADH.

NADPH that can be used as source of electrons in biosynthesis of

fatty acids and steroids.

Reduction of hydrogen peroxide:

• Hydrogen peroxide and other reactive oxygen intermediates are

highly reactive and can cause serious damages, eact with double

bonds in fatty acid moieties of membrane lipids, making

membranes leaky. •The cell has several protective mechanisms that

serve to minimize the toxic potential f these

compounds.

enzymes that catalyze antioxidant reactions:

Reduced glutathione can chemically detoxify

hydrogen peroxide. Regeneration of glutathione

reductase from the oxidizes form utilizes NADPH as

source of electrons.

Page 9: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

The cell has several protective mechanisms that serve to minimize the toxic

potential f these compounds.

I) Enzymes that catalyze antioxidant reactions:Glutathione is a tripeptide that includes cysteine. Its functional group is the cysteine thiol.Glutathione has a role in degradation of hydroperoxides that arise

spontaneously in the oxygen-rich environment within red blood cells.Reduced glutathione can chemically detoxify hydrogen peroxide . this

reaction catalyzed by glutathione peroxidase forms oxidized glutathione.The cell regenerate reduced glutathione in a reaction catalyzed by

electrons thus NADPH indirectly provides electrons for the reduction of

hydrogen peroxide.

Page 10: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

Reduced glutathione can chemically detoxify hydrogen peroxide . This reaction is catalyzed by glutathione peroxidase. The cell regenerate reduced glutathione in a reaction catalyzed by

Glutathione Reductase NADPH indirectly provides electrons for the reduction of hydrogen

peroxide. 2 GSH + ROOH GSSG + ROH + H2O

GSSG + NADPH + H+ 2 GSH + NADP+

Page 11: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

II) Antioxidant chemicals:

A number of intracellular reducing agents, such as ascorbate, vitamin E and

-carotene are able to reduce and thus detoxify oxygen intermediates in cells

III) Cytochrome p-450 system:

NADPH is critical for the liver microsomal cytochrome P-450

monooxygenase system.

This is the major pathway for hydroxylation of aromatic and aliphatic

compounds, such as steroids, alcohols and many drugs.

These oxidations also serve to detoxify drugs and foreign compounds by

converting them into soluble forms more readily excreted through the kidney

Page 12: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

IV) Phagocytosis by white blood cells:

Neutrophils and monocytes have oxygen-

dependent and oxygen-independent mechanisms

for killing bacteria.

The oxygen-dependent mechanism include

the myeloperoxidase (MPO) system and

another system that involves the generation of

oxygen –derived free radicals.

Oxygen-independent systems utilize pH

changes in the phagolysosomes and lysosomal

enzymes to destroy pathogens.

After phagocytosis has occurred, NADPH oxidase,

converts molecular oxygen into superoxide. (the

respiratory burst). Next superoxide is converted

into hydrogen peroxide by superoxide dismutase

(SOD). In the presence of MPO, peroxide plus

chloride ions are converted into hypochlorous acid

that kills the bacteria.

Page 13: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

Glucose 6 phosphate dehydrogenase deficiency:

Glucose 6 phosphate dehydrogenase(G6PD) deficiency is an inherited

disease (X-linked disorder) characterized by hemolytic anemia caused by the

inability to detoxify oxidizing agents.

G6PD deficiency is the most common disease producing enzyme

abnormality in humans.

The life span of many individuals with G6PD deficiency is shortened as a

result of complications arising from chronic hemolysis.

It is most common in the Mediterranean, the Middle East, South East Asia

and West Africa. It is rare among Caucasians

Role of G6PD in red blood cells:

Diminished G6PD activity impairs the ability to form NADPH that is

essential in the detoxification of free radicals and peroxides formed within

the cell.

All cells of the affected individual have enzyme deficiency. But it is most

sever in erythrocytes where the HMP provides the only means of generating

NADPH.

Other tissues have other NADPH sources as NADP+ - dependent malate

dehydrogenase).

Page 14: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

Precipitating factors in G6PD deficiency:

Some factors precipitate the hemolytic anemia in G6PD deficiency patents:

1. Oxidant drugs: like antibiotics e.g; sulfamethoxazole, Antimalarials e.g;

premaquine

2. Favism: The hemolytic effect of ingesting fava beans is observed in

patients with favism (G6PD deficiency).

3. Infection: The inflammatory response to infection results in the generation

of free radicals in macrophages, which can diffuse into the red blood cells

and cause oxidative damage.

4. Neonatal jaundice:

Individuals with G6PD

deficiency may

experience neonatal

jaundice, which may

result from impaired

hepatic catabolism or

increased production

of bilirubin.

Page 15: Also called the pentose phosphate pathway, or phosphogluconate pathway  It consists of two irreversible oxidative reactions, followed by a series of

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