NADH peroxidase | |||||||||
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Identifiers | |||||||||
EC no. | 1.11.1.1 | ||||||||
CAS no. | 9032-24-0 | ||||||||
Databases | |||||||||
IntEnz | IntEnz view | ||||||||
BRENDA | BRENDA entry | ||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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In enzymology, a NADH peroxidase (EC 1.11.1.1) is an enzyme that catalyzes the chemical reaction
The presumed function of NADH peroxidase is to inactivate H2O2 generated within the cell, for example by glycerol-3-phosphate oxidase during glycerol metabolism or dismutation of superoxide, before the H2O2 causes damage to essential cellular components. [1]
The 3 substrates of this enzyme are NADH, H+, and H2O2, whereas its two products are NAD+ and H2O. It employs one cofactor, FAD, however no discrete FADH2 intermediate has been observed. [2]
This enzyme belongs to the family of oxidoreductases, specifically those acting on a peroxide as acceptor (peroxidases). The systematic name of this enzyme class is NADH:hydrogen-peroxide oxidoreductase. Other names in common use include DPNH peroxidase, NAD peroxidase, diphosphopyridine nucleotide peroxidase, NADH-peroxidase, nicotinamide adenine dinucleotide peroxidase, and NADH2 peroxidase.
The crystal structure of NADH peroxidase resembles glutathione reductase with respect to chain fold and location as well as conformation of the prosthetic group FAD [3]
His10 of the NADH peroxidase is located near the N-terminus of the R1 helix within the FAD-binding site. [4] One of the oxygen atoms of Cys42-SO3H is hydrogen-bonded both to the His10 imidazole and to Cys42 N terminus. The His10 functions in part to stabilize the unusual Cys42-SOH redox center. [3] Arg303 also stabilizes the Cys42-SO3H. Glu-14 participates in forming the tight dimer interface that limits solvent accessibility, important for maintaining the oxidation state of the sulfenic acid. [4]
The NADH peroxidase from Enterococcus faecalis is unique in that it utilizes the Cys42 thiol/sulfenic acid (-SH/-SOH) redox couple in the heterolytic cleavage of the peroxide bond to catalyze the two-electron reduction of hydrogen peroxide to water. [5]
The kinetic mechanism of the wild-type peroxidase involves (1) NADH reduction of E(FAD, Cys42-SOH) to EH2(FAD, Cys42-SH) in an initial priming step; (2) rapid binding of NADH to EH2; (3) reduction of H2O2 by the Cys42-thiolate, yielding E•NADH; and (4) rate-limiting hydride transfer from bound NADH, regenerating EH2. [6] No discrete FADH2 intermediate has been observed, however, and the precise details of Cys42-SOH reduction have not been elucidated. [7]
Inhibitors include Ag+, Cl−, Co2+, Cu2+, Hg2+, NaN3, Pb2+, and SO42−. [8] At suboptimal H2O2 concentrations and concentrations of NADH that are saturating, NADH inhibits the peroxidase activity of the NADH peroxidase by converting the enzyme to an unstable intermediate. NAD+ behaves as an activator by reversing the equilibria that lead to the unstable intermediate, thus converting the enzyme to the kinetically active complex that reduces H2O2. [9]
NADH eliminates potentially toxic hydrogen peroxide under aerobic growth conditions and represents an enzymatic defense available against H2O2-mediated oxidative stress. Second, the enzyme presents an additional mechanism for regeneration of the NAD+ essential to the strictly fermentative metabolism of this organism. [2] [10] The enzyme may also protect against exogenous H2O2 and contribute to bacterial virulence. [11]
The actual function of NADH peroxidases and oxidases in plants is still unclear, but they could act in early signaling of oxidative stress through producing H2O2. [12]
An alternative role may include regulation of H2O2 formation by NADH peroxidase and oxidase in cell wall loosening and reconstruction. [13]
Hydrogen peroxide is a chemical compound with the formula H2O2. In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution in water for consumer use, and in higher concentrations for industrial use. Concentrated hydrogen peroxide, or "high-test peroxide", decomposes explosively when heated and has been used both as a monopropellant and an oxidizer in rocketry.
Catalase is a common enzyme found in nearly all living organisms exposed to oxygen which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting the cell from oxidative damage by reactive oxygen species (ROS). Catalase has one of the highest turnover numbers of all enzymes; one catalase molecule can convert millions of hydrogen peroxide molecules to water and oxygen each second.
A dehydrogenase is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN. Like all catalysts, they catalyze reverse as well as forward reactions, and in some cases this has physiological significance: for example, alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde in animals, but in yeast it catalyzes the production of ethanol from acetaldehyde.
The glucose oxidase enzyme also known as notatin is an oxidoreductase that catalyses the oxidation of glucose to hydrogen peroxide and D-glucono-δ-lactone. This enzyme is produced by certain species of fungi and insects and displays antibacterial activity when oxygen and glucose are present.
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP+ or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADPH as a reducing agent ('hydrogen source'). NADPH is the reduced form of NADP+, the oxidized form. NADP+ is used by all forms of cellular life.
The oxoglutarate dehydrogenase complex (OGDC) or α-ketoglutarate dehydrogenase complex is an enzyme complex, most commonly known for its role in the citric acid cycle.
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Any enzyme system that includes cytochrome P450 protein or domain can be called a P450-containing system.
Ascorbate peroxidase (or L-ascorbate peroxidase, APX) (EC 1.11.1.11) is an enzyme that catalyzes the chemical reaction
The glycerol-3-phosphate shuttle is a mechanism used in skeletal muscle and the brain that regenerates NAD+ from NADH, a by-product of glycolysis. The NADH generated during glycolysis is found in the cytoplasm and must be transported into the mitochondria to enter the oxidative phosphorylation pathway. However, the inner mitochondrial membrane is impermeable to NADH and NAD+ and does not contain a transport system for these electron carriers. Either the glycerol-3-phosphate shuttle pathway or the malate-aspartate shuttle pathway, depending on the tissue of the organism, must be taken to transport cytoplasmic NADH into the mitochondria. The shuttle consists of the sequential activity of two proteins; Cytoplasmic glycerol-3-phosphate dehydrogenase (cGPD) transfers an electron pair from NADH to dihydroxyacetone phosphate (DHAP), forming glycerol-3-phosphate (G3P) and regenerating NAD+ needed to generate energy via glycolysis. The other protein, mitochondrial glycerol-3-phosphate dehydrogenase (mGPD) catalyzes the oxidation of G3P by FAD, regenerating DHAP in the cytosol and forming FADH2 in the mitochondrial matrix. In mammals, its activity in transporting reducing equivalents across the mitochondrial membrane is considered secondary to the malate-aspartate shuttle.
4-hydroxyphenylacetate 3-monooxygenase (EC 1.14.14.9) is an enzyme that catalyzes the chemical reaction
In enzymology, a malate oxidase (EC 1.1.3.3) is an enzyme that catalyzes the chemical reaction
In enzymology, a fatty-acid peroxidase (EC 1.11.1.3) is an enzyme that catalyzes the chemical reaction
In enzymology, a lignin peroxidase (EC 1.11.1.14) is an enzyme that catalyzes the chemical reaction
In enzymology, a manganese peroxidase (EC 1.11.1.13) is an enzyme that catalyzes the chemical reaction
In enzymology, a NADPH peroxidase (EC 1.11.1.2) is an enzyme that catalyzes the chemical reaction
Renalase, FAD-dependent amine oxidase is an enzyme that in humans is encoded by the RNLS gene. Renalase is a flavin adenine dinucleotide-dependent amine oxidase that is secreted into the blood from the kidney.
Hypothiocyanite is the anion [OSCN]− and the conjugate base of hypothiocyanous acid (HOSCN). It is an organic compound part of the thiocyanates as it contains the functional group SCN. It is formed when an oxygen is singly bonded to the thiocyanate group. Hypothiocyanous acid is a fairly weak acid; its acid dissociation constant (pKa) is 5.3.
Lactoperoxidase is a peroxidase enzyme secreted from mammary, salivary and other mucosal glands including the lungs, bronchii and nose that functions as a natural and the first line of defense against bacteria and viruses. Lactoperoxidase is a member of the heme peroxidase family of enzymes. In humans, lactoperoxidase is encoded by the LPO gene.
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