also called the pentose phosphate pathway, or phosphogluconate pathway it consists of two...
Post on 02-Jan-2016
222 Views
Preview:
TRANSCRIPT
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
Hexose Monophosphate Pathway
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
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
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
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
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
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.
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.
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+
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
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.
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).
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.
The end
top related