Glucose-6-phosphate dehydrogenase (
G6PD) is a cytosolic
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
in the
pentose phosphate pathwayThe pentose phosphate pathway is a process that generates NADPH and pentoses sugars. There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis of 5-carbon sugars...
(see image), a
metabolic pathway-Cellular respiration:Several distinct but linked metabolic pathways are used by cells to transfer the energy released by breakdown of fuel molecules to ATP...
that supplies reducing energy to cells (such as erythrocytes) by maintaining the level of the co-enzyme
nicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide, abbreviated NAD
+, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups, with one nucleotide containing an adenine base and the other containing...
(NADPH). The NADPH in turn maintains the level of
glutathioneGlutathione is a tripeptide. It contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side chain. Glutathione, an antioxidant, helps protect cells from reactive oxygen species such as free radicals and peroxides...
in these cells that helps protect the red blood cells against oxidative damage. Of greater quantitative importance is the production of NADPH for tissues actively engaged in biosynthesis of fatty acids and/or isoprenoids, such as the liver, mammary glands, adipose tissue, and the adrenal glands.
It is notable in humans when there is a
genetic deficiencyGlucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of glucose-6-phosphate dehydrogenase , a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism...
which predisposes to non-immune haemolytic anaemia.
G6PD is widely distributed in many species from bacteria to man.
Glucose-6-phosphate dehydrogenase (
G6PD) is a cytosolic
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
in the
pentose phosphate pathwayThe pentose phosphate pathway is a process that generates NADPH and pentoses sugars. There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis of 5-carbon sugars...
(see image), a
metabolic pathway-Cellular respiration:Several distinct but linked metabolic pathways are used by cells to transfer the energy released by breakdown of fuel molecules to ATP...
that supplies reducing energy to cells (such as erythrocytes) by maintaining the level of the co-enzyme
nicotinamide adenine dinucleotide phosphateNicotinamide adenine dinucleotide, abbreviated NAD
+, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups, with one nucleotide containing an adenine base and the other containing...
(NADPH). The NADPH in turn maintains the level of
glutathioneGlutathione is a tripeptide. It contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side chain. Glutathione, an antioxidant, helps protect cells from reactive oxygen species such as free radicals and peroxides...
in these cells that helps protect the red blood cells against oxidative damage. Of greater quantitative importance is the production of NADPH for tissues actively engaged in biosynthesis of fatty acids and/or isoprenoids, such as the liver, mammary glands, adipose tissue, and the adrenal glands.
It is notable in humans when there is a
genetic deficiencyGlucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of glucose-6-phosphate dehydrogenase , a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism...
which predisposes to non-immune haemolytic anaemia.
Species distribution
G6PD is widely distributed in many species from bacteria to man. In higher plants, several isoforms of G6PDH have been reported, which are localized in the cytosol, the plastidic stroma, and peroxisomes.
Regulation
Glucose-6-phosphate dehydrogenase is stimulated by its substrate Glucose 6 Phosphate. The usual ratio of NADPH/NADP
+ in the cytosol of tissues engaged in biosyntheses is about 100/1. Increased utilization of NADPH for fatty acid biosynthesis will dramatically increase the level of NADP
+, thus stimulating
G6PD to produce more NADPH.
G6PD converts
glucose-6-phosphateGlucose 6-phosphate is glucose sugar phosphorylated on carbon 6. This compound is very common in cells as the vast majority of glucose entering a cell will become phosphorylated in this way....
into 6-phosphoglucono-δ-lactone and is the rate-limiting enzyme of the
pentose phosphate pathway.
Clinical significance
G6PD is remarkable for its genetic diversity. Many variants of G6PD, mostly produced from
missense mutationIn genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid. This can render the resulting protein nonfunctional...
s, have been described with wide ranging levels of enzyme activity and associated clinical symptoms. Two transcript variants encoding different isoforms have been found for this gene.
Glucose-6-phosphate dehydrogenase deficiencyGlucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of glucose-6-phosphate dehydrogenase , a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism...
is very common worldwide, and cause acute
hemolytic anemiaHemolytic anemia is anemia due to hemolysis, the abnormal breakdown of red blood cells either in the blood vessels or elsewhere in the body . It has numerous possible causes, ranging from relatively harmless to life-threatening. The general classification of hemolytic anemia is either acquired or...
in the presence of simple infection, ingestion of fava beans, or reaction with certain medicines, AAA, antibiotics, antipyretics, and antimalarials.
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