Glucose-6-phosphate dehydrogenase (G6PD) is a cytosolic enzyme Enzymes 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 significant rates. Since enzymes are selective for their in the pentose phosphate pathway The pentose phosphate pathway is a process that generates NADPH and pentoses (5-carbon 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. This pathway is an alternative to glycolysis. While it does involve oxidation (see image), a metabolic pathway In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function properly. Because of the many chemicals that may be involved, that supplies reducing energy to cells (such as erythrocytes Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen (O2) to the body tissues via the blood flow through the circulatory system. They take up oxygen in the lungs or gills and release it while squeezing through the body's capillaries) by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate Nicotinamide 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 nicotinamide (NADPH). The NADPH in turn maintains the level of glutathione Glutathione 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 Redox describes all chemical reactions in which atoms have their oxidation number (oxidation state) changed. This can be either a simple redox process, such as the oxidation of carbon to yield carbon dioxide (CO2) or the reduction of carbon by hydrogen to yield methane (CH4), or a complex process such as the oxidation of sugar(C6H12O6) in the 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 deficiency Glucose-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. Individuals with the disease may exhibit nonimmune hemolytic anemia which predisposes to non-immune haemolytic anaemia Hemolytic anemia is anemia due to hemolysis, the abnormal breakdown of red blood cells either in the blood vessels (intravascular hemolysis) or elsewhere in the body (extravascular). It has numerous possible causes, ranging from relatively harmless to life-threatening. The general classification of hemolytic anemia is either acquired or inherited.

Contents

Species distribution

G6PD is widely distributed in many species from bacteria The bacteria ( [bækˈtɪəriə] ; singular: bacterium)[α] are a large group of single-celled, prokaryote microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals. Bacteria are ubiquitous in every habitat on Earth, growing in soil, acidic hot springs, radioactive waste, to humans Humans, known taxonomically as Homo sapiens , are the only living species in the Homo genus of bipedal primates in Hominidae, the great ape family. However, in some cases "human" is used to refer to any member of the genus Homo. In higher plants, several isoforms A protein isoform is any of several different forms of the same protein. Different forms of a protein may be produced from related genes, or may arise from the same gene by alternative splicing. A large number of isoforms are caused by single-nucleotide polymorphisms or SNPs, small genetic differences between alleles of the same gene. These occur of G6PDH have been reported, which are localized in the cytosol The cytosol or intracellular fluid is the liquid found inside cells. In eukaryotes this liquid is separated by cell membranes from the contents of the organelles suspended in the cytosol, such as the mitochondrial matrix inside the mitochondrion. The entire contents of a eukaryotic cell within cell membrane, minus the contents of the cell nucleus,, the plastidic stroma, and peroxisomes Peroxisomes are organelles from the microbody family and are present in almost all eukaryotic cells. They participate in the metabolism of fatty acids and many other metabolites. Peroxisomes harbor enzymes that rid the cell of toxic peroxides. Peroxisomes are bound by a single membrane that separates their contents from the cytosol and contain.[1]

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-phosphate Glucose 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 mutations, have been described with wide ranging levels of enzyme activity Enzyme assays are laboratory methods for measuring enzymatic activity. They are vital for the study of enzyme kinetics and enzyme inhibition and associated clinical symptoms. Two transcript variants encoding different isoforms A protein isoform is any of several different forms of the same protein. Different forms of a protein may be produced from related genes, or may arise from the same gene by alternative splicing. A large number of isoforms are caused by single-nucleotide polymorphisms or SNPs, small genetic differences between alleles of the same gene. These occur have been found for this gene.[2]

Glucose-6-phosphate dehydrogenase deficiency Glucose-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. Individuals with the disease may exhibit nonimmune hemolytic anemia is very common worldwide, and causes acute hemolytic anemia Hemolytic anemia is anemia due to hemolysis, the abnormal breakdown of red blood cells either in the blood vessels (intravascular hemolysis) or elsewhere in the body (extravascular). It has numerous possible causes, ranging from relatively harmless to life-threatening. The general classification of hemolytic anemia is either inherited or acquired in the presence of simple infection, ingestion of fava beans, or reaction with certain medicines, AAA, antibiotics, antipyretics, and antimalarials.[3]

See also

References

  1. ^ Corpas FJ et al. (1998). "A dehydrogenase-mediated recycling system of NADPH in plant peroxisomes". Biochem. J.. 330 (7): 777–784.
  2. ^ "Entrez Gene: G6PD glucose-6-phosphate dehydrogenase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2539.
  3. ^ Cappellini MD, Fiorelli G (January 2008). "Glucose-6-phosphate dehydrogenase deficiency". Lancet 371 (9606): 64–74. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1016/S0140-6736(08)60073-2. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 18177777.

Further reading

External links

PDB Gallery
1qki: X-RAY STRUCTURE OF HUMAN GLUCOSE 6-PHOSPHATE DEHYDROGENASE (VARIANT CANTON R459L) COMPLEXED WITH STRUCTURAL NADP+
2bh9: X-RAY STRUCTURE OF A DELETION VARIANT OF HUMAN GLUCOSE 6-PHOSPHATE DEHYDROGENASE COMPLEXED WITH STRUCTURAL AND COENZYME NADP
2bhl: X-RAY STRUCTURE OF HUMAN GLUCOSE-6-PHOSPHATE DEHYDROGENASE (DELETION VARIANT) COMPLEXED WITH GLUCOSE-6-PHOSPHATE
Oxidoreductases In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule to another (the oxidant, also called the hydrogen or electron acceptor): alcohol oxidoreductases (EC The Enzyme Commission number is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. As a system of enzyme nomenclature, every EC number is associated with a recommended name for the respective enzyme 1.1)
1.1.1 This list contains a list of EC numbers for the first group, EC 1, oxidoreducatases, placed in numerical order as determined by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology: NAD Nicotinamide 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 nicotinamide/NADP Nicotinamide adenine dinucleotide phosphate is used in anabolic reactions, such as lipid and nucleic acid synthesis, which require NADPH as a reducing agent acceptor

Alcohol dehydrogenase Alcohol dehydrogenases (EC 1.1.1.1) are a group of seven dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of NAD+ to NADH. In humans and many other animals, they serve to break down alcohols which could otherwise be toxic; in yeast, plants and many · Aldo-keto reductase (1A1, 1B1 Aldo-keto reductase family 1, member B1 , also known as AR, is an enzyme that in humans is encoded by the AKR1B1 gene, 1B10, 1C1, 1C3, 1C4, 7A2) · Aldose reductase · Carbohydrate dehydrogenases · Carnitine dehydrogenase · DXP reductoisomerase · Glucose-6-phosphate dehydrogenase · Glycerol-3-phosphate dehydrogenase Glycerol-3-phosphate dehydrogenase is an enzyme that catalyzes the reduction of dihydroxyacetone phosphate (aka glycerone phosphate, outdated) to sn-glycerol 3-phosphate · HMG-CoA reductase HMG-CoA reductase is the rate controlling enzyme (EC 1.1.1.88) of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids. This enzyme is the target of the widely available cholesterol lowering drugs known collectively as the statins. HMG-CoA reductase is anchored in the membrane of the endoplasmic reticulum, · 3-Hydroxyacyl CoA dehydrogenase · Beta-hydroxybutyryl-CoA dehydrogenase · Isocitrate dehydrogenase · IMP dehydrogenase · Β-Ketoacyl ACP reductase · Lactate dehydrogenase Lactate dehydrogenase is an enzyme (EC 1.1.1.27) present in a wide variety of organisms, including plants and animals · Malate dehydrogenase · Phosphogluconate dehydrogenase · L-threonine dehydrogenase · L-xylulose reductase · Sorbitol dehydrogenase

Hydroxysteroid dehydrogenase: 3 Beta (3-beta-HSD, NSDHL) · 11 Beta (HSD11B1, HSD11B2) · 17 Beta
1.1.2 This list contains a list of EC numbers for the first group, EC 1, oxidoreducatases, placed in numerical order as determined by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology: cytochrome Cytochromes are, in general, membrane-bound hemoproteins that contain heme groups and carry out electron transport acceptor D-lactate dehydrogenase (cytochrome) · D-lactate dehydrogenase (cytochrome c-553) · Mannitol dehydrogenase (cytochrome)
1.1.3 This list contains a list of EC numbers for the first group, EC 1, oxidoreducatases, placed in numerical order as determined by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology: oxygen Oxygen (pronounced /ˈɒksɨdʒɨn/, OK-si-jin, from the Greek roots ὀξύς (acid, literally "sharp", from the taste of acids) and -γενής (-genēs) (producer, literally begetter), is the element with atomic number 8 and represented by the symbol O. It is a member of the chalcogen group on the periodic table, and is a highly acceptor Glucose oxidase · L-gulonolactone oxidase · Xanthine oxidase Xanthine oxidase (XO , a form of xanthine oxidoreductase that generates reactive oxygen species) is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid. This enzyme plays an important role in the catabolism of purines in some species, including humans
1.1.4 This list contains a list of EC numbers for the first group, EC 1, oxidoreducatases, placed in numerical order as determined by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology: disulfide In chemistry, a disulfide usually refers to the structural unit composed of a linked pair of sulfur atoms. Disulfide usually refer to a chemical compound that contains a disulfide bond, such as diphenyl disulfide, C6H5S-SC6H5 as acceptor Vitamin K epoxide reductase Vitamin K epoxide reductase is an enzyme (EC 1.1.4.1) that reduces vitamin K after it has been oxidised in the carboxylation of glutamic acid. Its C1 subunit (VKORC1) is the target of anticoagulant warfarin · Vitamin-K-epoxide reductase (warfarin-insensitive)
1.1.5 This list contains a list of EC numbers for the first group, EC 1, oxidoreducatases, placed in numerical order as determined by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology: quinone A quinone is a class of organic compounds that are formally derived from aromatic compounds by exchanging an even number of –CH= groups by –C(=O)– groups, with any necessary rearrangement of double bonds, resulting in a fully conjugated cyclic dione structure. The class includes derivatives of heterocyclic aromatic compounds/similar acceptor Quinoprotein glucose dehydrogenase
1.1.99 This list contains a list of EC numbers for the first group, EC 1, oxidoreducatases, placed in numerical order as determined by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology: other acceptors Choline dehydrogenase · L2HGDH
Metabolism Metabolism is the set of chemical reactions that happen in living organisms to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism breaks down organic matter, for example to harvest energy in cellular: carbohydrate metabolism Carbohydrate metabolism denotes the various biochemical processes responsible for the formation, breakdown and interconversion of carbohydrates in living organisms - pentose phosphate pathway The pentose phosphate pathway is a process that generates NADPH and pentoses (5-carbon 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. This pathway is an alternative to glycolysis. While it does involve oxidation enzymes
oxidative Glucose-6-phosphate dehydrogenase - 6-phosphogluconolactonase - Phosphogluconate dehydrogenase
nonoxidative Phosphopentose isomerase - Phosphopentose epimerase - Transketolase - Transaldolase
see also ,
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