Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.4 (SOR)
 720 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary methemoglobinemia with generalized deficiency of NADH-cytochrome b5 reductase (b5R) (type II) is a rare disease characterized by severe developmental abnormalities, which often lead to premature death. Although the molecular relationship between the symptoms of this condition and the enzyme deficit are not understood, it is thought that an important cause is the loss of the lipid metabolizing activities of the endoplasmic reticulum-located reductase. However, the functions of the form located on outer mitochondrial membranes have not been considered previously. In this study, we have analyzed the gene of an Italian patient and identified a novel G-->T transversion at the splice-acceptor site of the 9th exon, which results in the complete absence of immunologically detectable b5R in blood cells and skin fibroblasts. In cultured fibroblasts of the patient, NADH-dependent cytochrome c reductase, ferricyanide reductase, and semidehydroascorbate reductase activities were severely reduced. The latter activity is known to be due to b5R located on outer mitochondrial membranes. Thus, our results demonstrate that the reductase in its two membrane locations, endoplasmic reticulum and outer mitochondrial membranes, is the product of the same gene and suggest that a defect in ascorbate regeneration may contribute to the phenotype of hereditary methemoglobinemia of the generalized type.
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PMID:A novel point mutation in a 3' splice site of the NADH-cytochrome b5 reductase gene results in immunologically undetectable enzyme and impaired NADH-dependent ascorbate regeneration in cultured fibroblasts of a patient with type II hereditary methemoglobinemia. 766 55

A specific requirement for coenzyme Q in the maintenance of trans-plasma-membrane redox activity is demonstrated. Extraction of coenzyme Q from membranes resulted in inhibition of NADH-ascorbate free radical reductase (trans electron transport), and addition of coenzyme Q10 restored the activity. NADH-cytochrome c oxidoreductase (cis electron transport) did not respond to the coenzyme Q status. Quinone analogs inhibited trans-plasma-membrane redox activity, and the inhibition was reversed by coenzyme Q. A 34-kDa coenzyme Q reductase (p34) has been purified from pig-liver plasma membranes. The isolated enzyme was sensitive to quinone-site inhibitors. p34 catalyzed the NADH-dependent reduction of coenzyme Q10 after reconstitution in phospholipid liposomes. When plasma membranes were supplemented with extra p34, NADH-ascorbate free radical reductase was activated but NADH-cytochrome c oxidoreductase was not. These results support the involvement of p34 as a source of electrons for the trans-plasma-membrane redox system oxidizing NADH and support coenzyme Q as an intermediate electron carrier between NADH and the external acceptor ascorbate free radical.
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PMID:Coenzyme Q reductase from liver plasma membrane: purification and role in trans-plasma-membrane electron transport. 776 18

Plasma membranes purified by two-phase partition from rat liver showed an NADH-ascorbate free radical reductase activity of about 14 nmoles NADH oxidized/min/mg protein. This activity was inhibited by N-ethyl maleimide, iodoacetate and iodoacetamide, reagents that covalently block thiol groups. NADH-ascorbate free radical reductase was also inhibited by reduced glutathione and the inhibitions observed with blocking reagents and reduced compounds were additive. These results support the involvement of sulphydryl groups in NADH-AFR reductase and point out the idea that a balance between reduced sulfhydryls and oxidized disulfides is required for the optimal function of this activity, considered as part of the transplasma membrane electron transport system.
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PMID:Thiol groups are involved in NADH-ascorbate free radical reductase activity of rat liver plasma membrane. 848 77

The glyoxysomes of growing oilseed seedlings produce H2O2, a reactive oxygen species, during the beta-oxidation of lipids stored in the cotyledons. An expression library of dark-grown cotton (Gossypium hirsutm L.) cotyledons was screened with antibodies that recognized a 31-kD glyoxysomal membrane polypeptide. A full-length cDNA clone (1258 bp) was isolated that encodes a 32-kD subunit of ascorbate peroxidase (APX) with a single, putative membrane-spanning region near the C-terminal end of the polypeptide. Internal amino acid sequence analysis of the cotton 31-kD polypeptide verified that this clone encoded this protein. This enzyme, designated gmAPX, was immunocytochemically and enzymatically localized to the glyoxysomal membrane in cotton cotyledons. The activity of monodehydroascorbate reductase, a protein that reduces monodehydroascorbate to ascorbate with NADH, also was detected in these membranes. The co-localization of gmAPX and monodehydroascorbate reductase within the glyoxysomal membrane likely reflects an essential pathway for scavenging reactive oxygen species and also provides a mechanism to regenerate NAD+ for the continued operation of the glyoxylate cycle and beta-oxidation of fatty acids. Immunological cross-reactivity of 30- to 32-kD proteins in glyoxysomal membranes of cucumber, sunflower, castor bean, and cotton indicate that gmAPX is common among oilseed species.
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PMID:Ascorbate peroxidase. A prominent membrane protein in oilseed glyoxysomes. 874 35

Long-term treatment with ethidium bromide of HL-60 cells induced a mitochondria-deficient rho degree cell line, where mitochondrial DNA can not be identified by PCR and cytochrome c oxidase activity was 80% decreased. These cells showed a progressive increase of ascorbate stabilization which was 52% higher in the established rho degree HL-60 cells. Both CoQ10 and NADH-ascorbate free radical reductase of the plasma membrane were increased in rho(0)HL-60 cells compared to parental cells, while NADH-cytochrome c reductase was unchanged. CoQ10 is a component of the ascorbate stabilization activity in the plasma membrane that would provide both a mechanism to deplete the excess of NADH produced in rho(0)HL-60 cells and for resistance to oxidative stress.
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PMID:Ascorbate stabilization is stimulated in rho(0)HL-60 cells by CoQ10 increase at the plasma membrane. 916 64

Cytochrome b5 reductase purified from liver plasma membrane reduces coenzyme Q (CoQ) in reconstituted liposomes in the absence of cytochrome b5. Both CoQ and its reductase are responsible for the reduction of the ascorbate free radical at the cell surface. Thus, NADH-CoQ reductase represents a partial reaction of NADH-AFR reductase in the plasma membrane. Cytochrome b5 reductase maintains CoQ and ascorbate in their reduced state to support antioxidations. Reduced CoQ prevents lipid peroxidation in liposomes and plasma membranes. Also, oxidized CoQ can prevent lipid peroxidations in the presence of cytochrome b5 reductase and NADH. Addition of CoQ to intact cells prevents serum withdrawal-induced lipid peroxidation and apoptosis. The prevention of apoptosis by CoQ is independent of the bcl-2 protein content in the cell. Antioxidants that act at the plasma membrane as CoQ and ascorbate would represent a first barrier to protect lipids from oxidative stress and subsequent apoptosis. Cytochrome b5 reductase is then an enzyme leading this function at the plasma membrane. These data support the idea that when the plasma membrane barrier fails, bcl-2 protein would be required to prevent cell death.
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PMID:Role of cytochrome b5 reductase on the antioxidant function of coenzyme Q in the plasma membrane. 926 1

Plasma membranes isolated from K562 cells contain an NADH-ascorbate free radical reductase activity and intact cells show the capacity to reduce the rate of chemical oxidation of ascorbate leading to its stabilization at the extracellular space. Both activities are stimulated by CoQ10 and inhibited by capsaicin and dicumarol. A 34-kDa protein (p34) isolated from pig liver plasma membrane, displaying NADH-CoQ10 reductase activity and its internal sequence being identical to cytochrome b5 reductase, increases the NADH-ascorbate free radical reductase activity of K562 cells plasma membranes. Also, the incorporation of this protein into K562 cells by p34-reconstituted liposomes also increased the stabilization of ascorbate by these cells. TPA-induced differentiation of K562 cells increases ascorbate stabilization by whole cells and both NADH-ascorbate free radical reductase and CoQ10 content in isolated plasma membranes. We show here the role of CoQ10 and its NADH-dependent reductase in both plasma membrane NADH-ascorbate free radical reductase and ascorbate stabilization by K562 cells. These data support the idea that besides intracellular cytochrome b5-dependent ascorbate regeneration, the extracellular stabilization of ascorbate is mediated by CoQ10 and its NADH-dependent reductase.
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PMID:Antioxidant ascorbate is stabilized by NADH-coenzyme Q10 reductase in the plasma membrane. 929 10

Amino acid analysis of internal sequences of purified NADH-hexacyanoferrate(III) oxidoreductase (NFORase), obtained from highly purified plasma membranes (PM) of spinach (Spinacia oleracea L.) leaves, showed 90 to 100% homology to internal amino acid sequences of monodehydroascorbate (MDA) reductases (EC 1.6.5.4) from three different plant species. Specificity, kinetics, inhibitor sensitivity, and cross-reactivity with anti-MDA reductase antibodies were all consistent with this identification. The right-side-out PM vesicles were subjected to consecutive salt washing and detergent (polyoxyethylene 20 dodecylether and 3-[(3-cholamido-propyl)-dimethylammonio]-1-propane sulfonate [CHAPS]) treatments, and the fractions were analyzed for NFORase and MDA reductase activities. Similar results were obtained when the 300 mm sucrose in the homogenization buffer and in all steps of the salt-washing and detergent treatments had been replaced by 150 mm KCl to mimic the conditions in the cytoplasm. We conclude that (a) MDA reductase is strongly associated with the inner (cytoplasmic) surface of the PM under in vivo conditions and requires washing with 1.0 m KCl or CHAPS treatment for removal, (b) the PM-bound MDA reductase activity is responsible for the majority of PM NFORase activity, and (c) there is another redox enzyme(s) in the spinach leaf PM that cannot be released from the PM by salt-washing and/or CHAPS treatment. The PM-associated MDA reductase may have a role in reduction of ascorbate in both the cytosol and the apoplast.
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PMID:NADH-Monodehydroascorbate oxidoreductase is one of the redox enzymes in spinach leaf plasma membranes 950 Nov 35

We investigated the relationship between H2O2 metabolism and the senescence process using soluble fractions, mitochondria, and peroxisomes from senescent pea (Pisum sativum L.) leaves. After 11 d of senescence the activities of Mn-superoxide dismutase, dehydroascorbate reductase (DHAR), and glutathione reductase (GR) present in the matrix, and ascorbate peroxidase (APX) and monodehydroascorbate reductase (MDHAR) activities localized in the mitochondrial membrane, were all substantially decreased in mitochondria. The mitochondrial ascorbate and dehydroascorbate pools were reduced, whereas the oxidized glutathione levels were maintained. In senescent leaves the H2O2 content in isolated mitochondria and the NADH- and succinate-dependent production of superoxide (O2.-) radicals by submitochondrial particles increased significantly. However, in peroxisomes from senescent leaves both membrane-bound APX and MDHAR activities were reduced. In the matrix the DHAR activity was enhanced and the GR activity remained unchanged. As a result of senescence, the reduced and the oxidized glutathione pools were considerably increased in peroxisomes. A large increase in the glutathione pool and DHAR activity were also found in soluble fractions of senescent pea leaves, together with a decrease in GR, APX, and MDHAR activities. The differential response to senescence of the mitochondrial and peroxisomal ascorbate-glutathione cycle suggests that mitochondria could be affected by oxidative damage earlier than peroxisomes, which may participate in the cellular oxidative mechanism of leaf senescence longer than mitochondria.
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PMID:Role of the ascorbate-glutathione cycle of mitochondria and peroxisomes in the senescence of pea leaves 984 6

The production of superoxide radicals (O2(-).) and the activities of ferricyanide reductase and cytochrome c reductase were investigated in peroxisomal membranes from pea (Pisum sativum L.) leaves using NADH and NADPH as electron donors. The generation of O2(-). by peroxisomal membranes was also assayed in native polyacrylamide gels using an in situ staining method with NitroBlue Tetrazolium (NBT). When peroxisomal membranes were assayed under native conditions using NADH or NADPH as inducer, two different O2(-).-dependent Formazan Blue bands were detected. Analysis by SDS/PAGE of these bands demonstrated that the NADH-induced NBT reduction band contained several polypeptides (PMP32, PMP61, PMP56 and PMP18, where PMP is peroxisomal membrane polypeptide and the number indicates molecular mass in kDa), while the NADPH-induced band was due exclusively to PMP29. PMP32 and PMP29 were purified by preparative SDS/PAGE and electroelution. Reconstituted PMP29 showed cytochrome c reductase activity and O2(-). production, and used NADPH specifically as electron donor. PMP32, however, had ferricyanide reductase and cytochrome c reductase activities, and was also able to generate O2(-). with NADH as electron donor, whereas NADPH was not effective as an inducer. The reductase activities of, and O2(-). production by, PMP32 were inhibited by quinacrine. Polyclonal antibodies against cucumber monodehydroascorbate reductase (MDHAR) recognized PMP32, and this polypeptide is likely to correspond to the MDHAR reported previously in pea leaf peroxisomal membranes.
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PMID:Characterization of membrane polypeptides from pea leaf peroxisomes involved in superoxide radical generation. 989 98


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