There are three distinct origins of methaemoglobinaemia; the presence of a haemoglobin variant, environmental toxicity and deficiency of cytochrome b5 reductase (cb(5)r).
Expression of a novel P275L variant of NADH:cytochrome b5 reductase gives functional insight into the conserved motif important for pyridine nucleotide binding.
To understand these changes at a structural level, we have determined the structure of the S127P mutant of rat cytochrome b(5) reductase to 1.8 A resolution, providing the first structural snapshot of a cytochrome b(5) reductase mutant that causes methemoglobinemia.
Hereditary enzymopenic methemoglobinemia is a rare disease that predominantly results from defects in either the erythrocytic (type I) or microsomal (type II) forms of the enzyme NADH:cytochrome b5 reductase (EC 1.6.2.2).
A case of type I methaemoglobinaemia observed in a Polish subject with compound heterozygosity for two mutations in the reduced nicotinamide adenine dinucleotide (NADH) cytochrome b5 reductase (b5R) gene is described.
The patient and several members of her family showed decreased activities of erythrocyte NADH-cytochrome b5 reductase, predisposing them to the development of clinically significant methaemoglobinaemia when challenged with oxidant drugs.
Ferricyanide reductase assay can be substituted for assay of cytochrome b5 reductase (EC 1.6.2.2), which plays a major role in reducing methaemoglobin in erythrocytes, and is defective specifically in the erythrocytes of patients with hereditary methaemoglobinaemia.
Analyis of met-form haemoglobins in human erythrocytes of normal adults and of a patient with hereditary methaemoglobinaemia due to deficiency of NADH-cytochrome b5 reductase.