The biochemistry of aromatic amines. 10. Enzymic N-hydroxylation of arylamines and conversion of arylhydroxylamines into o-aminophenols

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Abstract
Rabbit-liver microsomes metabolized 4-acet-amidobiphenyl by the following reactions 4-acetamidobiphenyl-[forward arrow]-(N-hydroxyacetamido)biphenyW4-(hydroxyamino)biphenyl4-amino-biphenyl[forward arrow] 4-amino-3-hydroxybiphenyl. The initial N-hydroxylation required NADPH and oxygen but maximum amounts of 4-(N-hydroxy-acetamido)biphenyl were obtained when NADH and potassium fluoride were also present. Potassium fluoride inhibits the deacetylation of 4-(N-hydroxyacetamido)biphenyl and thus reduces further metabolism. N-Acetyl-N-hydroxy metabolites were also identified from 2-acetamido-fluorene and N-acetyl-benzidine, but not from 2-acetamidonaphthalene or acetanilide, under conditions which gave maximum amounts of 4-(N-hydroxyacetamido)biphenyl from 4-acetamidobiphenyl. 4-(N-Hydroxyacetamido)biphenyl is converted into 4-acetamido-3-hydroxy-biphenyl by the soluble fraction of rat or rabbit liver, and N-hydroxy-acetanilide, 2-(N-hydroxyacetamido)-naphthalene and 2-(N-hydroxyacetamido)fluorene are also isomerized to the corresponding o-hydroxy derivatives.