Abstract:
:In the present study the inability of 1,4-benzoquinone to support NADPH-cytochrome reductase catalysed redox cycling was investigated. The results obtained demonstrate that NADPH-cytochrome reductase is able to initiate a rapid two-electron reduction of 1,4-benzoquinone resulting in formation of the hydroquinone. The intermediate one-electron reduced semiquinone form does not pass its electron on to molecular oxygen, i.e. giving rise to redox cycling, but is reduced by a second electron, either by NADPH-cytochrome reductase upon protonation of the semiquinone or through disproportionation, both giving rise to the two-electron reduced hydroquinone. At pH values below the pK alpha of the hydroquinone, the electrons of the hydroquinone are also not passed on to molecular oxygen due to efficient protonation. However, at pH values around or above the pK alpha (9.85) of the two-electron reduced hydroquinone form, significant redox cycling activity is observed in a 1,4-benzoquinone containing incubation. Further experiments demonstrate a similarity in both the concentration and pH dependence of 1,4-benzoquinone or 1,4-hydroquinone supported NADPH-cytochrome reductase catalysed redox cycling. From these observations it is concluded that 1,4-benzoquinone is able to redox cycle from its deprotonated two-electron reduced hydroquinone form, but only at relatively high pH values. Together the data provide an insight into why the NADPH-cytochrome reductase catalysed redox cycling of 1,4-benzoquinone is inhibited at physiological conditions, but initiated at increased pH values.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Boersma MG,Balvers WG,Boeren S,Vervoort J,Rietjens IMdoi
10.1016/0006-2952(94)90068-xsubject
Has Abstractpub_date
1994-06-01 00:00:00pages
1949-55issue
11eissn
0006-2952issn
1873-2968pii
0006-2952(94)90068-Xjournal_volume
47pub_type
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