Altered heme catabolism by heme oxygenase-1 caused by mutations in human NADPH cytochrome P450 reductase

作者：Pandey Amit V^*; Flueck Christa E; Mullis Primus E

来源：Biochemical and Biophysical Research Communications, 2010, 400(3): 374-378.

DOI：10.1016/j.bbrc.2010.08.072

• Heme oxygenase
• NADPH P450 reductase
• NADPH ferrihemoprotein oxidoreductase
• P450 reductase
• POR
• CPR
• Antley-Bixler syndrome
• Adrenal hyperplasia

Human heme oxygenase-1 (HO-1) carries out heme catabolism supported by electrons supplied from the NADPH through NADPH P450 reductase (POR, CPR) Previously we have shown that mutations in human POR cause a rare form of congenital adrenal hyperplasia In this study, we have evaluated the effects of mutations in POR on HO-1 activity We used purified preparations of wild type and mutant human POR and in vitro reconstitution with purified HO-1 to measure heme degradation in a coupled assay using biliverdin reductase. Here we show that mutations in POR found in patients may reduce HO-1 activity, potentially influencing heme catabolism in individuals carrying mutant POR alleles POR mutants Y181D, A457H, Y459H, V492E and R616X had total loss of HO-1 activity, while POR mutations A287P. C569Y and V608F lost 50-70% activity The POR variants P228L, R316W and G413S, A503V and G504R identified as polymorphs had close to WT activity Loss of HO-1 activity may result in increased oxidative neurotoxicity, anemia, growth retardation and iron deposition

• 出版日期2010-9-24