PubMed · 13445761
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P STRITTMATTER, S F VELICK. 1957. Microsomal cytochrome reductase.. https://doi.org/10.1016/0006-3002(57)90462-6
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The different forms of hereditary methemoglobinemia are described. Dominant hereditary methemoglobinemia (hemoglobin M diseases) is due to punctual mutations on the alpha or beta globin chain leading to its permanent oxidation. Recessive hereditary methemoglobinemia is due to a deficit of the NADH-cytochrome b5 reductase, with two different clinical presentations according to whether the deficit is limited to blood cells (type I) or is generalized (type II); the latter is extremely severe and justifies a prenatal diagnosis. Finally, the only known case of recessive hereditary methemoglobinemia due to a deficit of b5 cytochrome is quoted.
We previously reported findings that NADPH/cytochrome P450 reductase can generate superoxide anion radical (O2*-) from heterocyclic amines (HCA) and from many anticancer agents in vitro. Here we present more evidence in which O2*- is generated when recombinant human cytochrome b5 reductase (rh-Cytb5Rd) was incubated with HCAs such as IQ and MeIQ in the presence of NADH in vitro. This indicates that free radical generation by rh-Cytb5Rd in the presence of HCA may add new insight into the damage of DNA in addition to the previously known mechanism: interaction of activated HCA-intermediates to form DNA adduct.
OBJECTIVE: Our aim was to examine a possible correlation between drinking water nitrate concentration, recurrent stomatitis, and cytochrome b5 reductase activity. Dietary nitrate can form nitrite in vivo. This can cause methemoglobinemia in the red blood cells. Cytochrome b5 reductase is an enzyme in the red blood cells that reduces methemoglobin back to hemoglobin. METHODS: Five areas were selected in the State of Rajasthan, India, having drinking water nitrate concentration (as nitrate) of 26, 45, 95, 222, and 459 mg of NO3/L. House schedules were prepared in these areas in accordance with a statistically designed protocol. We selected 193 age- and weight-matched persons, representing 10% of the total population in each of these areas. Detailed history was taken for recurrent stomatitis, medical examination was conducted, and blood samples were taken to ascertain cytochrome b5 reductase activity in the selected population. Collected data were statistically analyzed to ascertain a relationship between nitrate concentration, cytochrome b5 reductase activity, and percent stomatitis, using Microsoft Excel software. RESULTS: This study suggests that there is a significant interdependence between drinking water nitrate concentration, cytochrome b5 reductase activity, and recurrent stomatitis. CONCLUSION: Increased cytochrome b5 reductase activity primarily induced by the presence of high nitrate concentration in drinking water could be the cause for recurrent stomatitis.