Disease relevance of CYB5R1

• Deficient cytochrome b5 reductase activity in nontoxic goiter with iodide organification defect [1].
• Altogether, these data show that the LCL are a favorable material for studying both types of cytochrome b5 reductase deficiency and for investigating in depth the molecular aspects of this metabolic disease [2].
• The total cytochrome b5 reductase activity of the control LCL was found to be similar whatever the LCL origin, except for one lymphoma line (Daudi) [2].
• In the present study we have investigated Epstein-Barr virus (EBV) transformed lymphoid cell lines (LCL) derived from patients with both types of cytochrome b5 reductase deficiency and from nondeficient individuals [2].
• Analysis of families segregating recessive congenital methemoglobinemia (RCM), a disease in which the cytochrome b5 reductase is defective, as well as of families with cases of hereditary low levels of cytochrome b5 reductase activity, confirmed that the locus responsible for RCM is on chromosome 22 [3].

Psychiatry related information on CYB5R1

• Generalised deficiency of cytochrome b5 reductase in congenital methaemoglobinaemia with mental retardation [4].

High impact information on CYB5R1

• Like the amphiphilic microsomal-bound cytochrome b5 reductase, the erythrocyte membrane-bound enzyme is solubilized by cathepsin D. Because this treatment is effective on unsealed ghosts but not on resealed (inside-in) ghosts, it is concluded that the enzyme is strongly bound to the inner face of the membrane [5].
• The enzyme from the control LCL (c 252/B 95) was found to be immunologically related to the human soluble erythrocyte cytochrome b5 reductase, indicating that it is the product of the same gene: the DIA1 (diaphorase) locus [2].
• NCB5OR is a highly conserved NAD(P)H reductase that contains a cytochrome b5-like domain at the N terminus and a cytochrome b5 reductase-like domain at the C terminus [6].
• We found no evidence of genetic heterogeneity between the families segregating RCM and the families exhibiting cases of low cytochrome b5 reductase activity [3].
• Congenital methemoglobinemia caused by an erythrocytic deficiency of cytochrome b5 reductase (b5R; type I) in African-American individuals was first reported by this laboratory [7].

Chemical compound and disease context of CYB5R1

• Hereditary methemoglobinemia due to reduced nicotinamide adenine dinucleotide (NADH) cytochrome b5 reductase (b5R) deficiency is classified into two types, an erythrocyte (type I) and a generalized (type II) [8].
• The structure of the S127P mutant of cytochrome b5 reductase that causes methemoglobinemia shows the AMP moiety of the flavin occupying the substrate binding site [9].
• RESULTS: This study suggests that there is a significant interdependence between drinking water nitrate concentration, cytochrome b5 reductase activity, and recurrent stomatitis [10].
• All 25 currently identified type I and type II methemoglobinemia mutants have been expressed in Escherichia coli using a novel six histidine-tagged rat cytochrome b5/cytochrome b5 reductase fusion protein designated NADH:cytochrome c reductase (H6NCR) [11].
• CONCLUSIONS: Heterozygosity for Cb5R deficiency may pre-dispose to methemoglobinemia even on a thrice-weekly regimen of dapsone [12].

Biological context of CYB5R1

• A cDNA coding for human liver NADH-cytochrome b5 reductase (cytochrome b5 reductase, EC 1.6.2.2) was cloned from a human liver cDNA library constructed in phage lambda gt11 [13].
• We conclude that the relative deficiency of soluble cytochrome-b5 reductase observed at birth is due to diminished post-translational processing of the membrane-bound enzyme during erythropoiesis of fetal cells [14].
• During the early phase of adaptation no differences in markers of lipid peroxidation were observed, but the activities of both cytochrome b5 reductase and glucose-6-phosphate dehydrogenase were significantly greater in deficient livers [15].
• Transient kinetics of intracomplex electron transfer in the human cytochrome b5 reductase-cytochrome b5 system: NAD+ modulates protein-protein binding and electron transfer [16].
• The results indicate that cytochrome b5 reductase is encoded by a single gene located on human chromosome 22 [17].

Anatomical context of CYB5R1

• Hereditary methemoglobinemia due to cytochrome b5 reductase deficiency in blood cells without associated neurologic and mental disorders [18].
• We found that red cells from cord blood and newborns exhibited a 50% decrease of soluble cytochrome-b5 reductase activity, whereas membrane-bound activity was in the adult range [14].
• Cytochrome b5 reductase activity in erythrocytes and leukocytes as related to sex and age [19].
• An enzyme with properties of a cytochrome b5 reductase accounted for most dicumarol-resistant quinone reductase activity in HL-60 plasma membranes [20].
• In support of this concept, COS-7 cells overexpressing cytochrome-b5 reductase displayed at least a 3-fold increase in the previously mentioned activity compared with mock-transfected cells [21].

Associations of CYB5R1 with chemical compounds

• These findings suggest the correlation of an iodide organification defect with a cytochrome b5 reductase deficiency [1].
• Consequently, it seems likely that the deficient cytochrome b5 reductase activity in this patient is due to a defect in the biosynthesis of FAD, the coenzyme of the reductase, from riboflavin [1].
• An exception was found for the invariant cysteine near the C terminus, which is found in all nitrate reductases and also in the closely related NADH: cytochrome b5 reductase, as well as, most other members of this flavoenzyme family [22].
• We conclude that neuroleptic medication reduces the expression of both the ubiquinone and cytochrome b5 reductase and among the effects of this reduction is a decrease in the production of neurotoxic superoxide [23].
• Phenazopyridine induced methaemoglobinaemia associated with decreased activity of erythrocyte cytochrome b5 reductase [24].

Other interactions of CYB5R1

• Both NQO1 and a novel dicumarol-insensitive quinone reductase that was not accounted by a cytochrome b5 reductase were significantly increased in plasma membranes after serum deprivation, showing a peak at 32 h of treatment [20].
• In this review G6PD, pyruvate kinase, 5' nucleotidase, and cytochrome b5 reductase deficiencies will be discussed in greater detail [25].
• A 1 mM concentration of NADPH or NADH greatly increased the extent of double-strand breakage by 0.01 microM FeBlm, suggesting roles for cytochrome P450 or cytochrome b5 reductase in strand breakage [26].
• Levels of cytochrome b5 reductase correlated (r = 0.59, P less than 0.01) with levels of the mitochondrial marker enzyme citrate synthase [27].
• Role of cytochrome b5 reductase on the antioxidant function of coenzyme Q in the plasma membrane [28].

Analytical, diagnostic and therapeutic context of CYB5R1

• Direct enzyme titration curve of NADH: cytochrome b5 reductase by combined isoelectric focusing/electrophoresis. Interactions between enzyme and cytochrome b5 [29].
• Prenatal diagnosis of congenital enzymopenic methaemoglobinaemia with mental retardation due to generalized cytochrome b5 reductase deficiency: first report of two cases [30].

References