Irreversible inactivation of macrophage and brain nitric oxide synthase by L-NG-methylarginine requires NADPH-dependent hydroxylation.

@article{Feldman1993IrreversibleIO,
  title={Irreversible inactivation of macrophage and brain nitric oxide synthase by L-NG-methylarginine requires NADPH-dependent hydroxylation.},
  author={Paul L. Feldman and Owen W. Griffith and H Hong and Dennis J. Stuehr},
  journal={Journal of medicinal chemistry},
  year={1993},
  volume={36 4},
  pages={491-6}
}
L-NG-Methylarginine (NMA) is an established mechanism-based inactivator of murine macrophage nitric oxide synthase (mNOS). In this report, NMA is shown to irreversibly inhibit both mNOS (k(inact) = 0.08 min-1) and the recombinant constitutive brain NOS (bNOS). For both NOS isoforms, metabolism of NMA parallels that of the natural substrate L-arginine (ARG), in that it undergoes a regiospecific, NADPH-dependent hydroxylation to form L-NG-hydroxy-NG-methylarginine (NOHNMA). This intermediate then… CONTINUE READING