The interactions of milacemide with monoamine oxidase.
The interactions of the anticonvulsant drug milacemide (2-n-pentylaminoacetamide) with rat liver mitochondrial monoamine oxidases-A and -B have been studied. The compound acts as a substrate for the B-form of the enzyme, with an apparent Km value of 49 +/- 4.7 microM and a Vmax value of 1.1 +/- 0.2 nmol/min/mg. It is also a time-dependent irreversible inhibitor of that enzyme. Any activity of monoamine oxidase-A towards this substrate was too low to allow accurate determinations to be made by either luminometric determination of H2O2 formation or spectrophotometric coupling of aldehyde formation to NAD+ reduction in the presence of aldehyde dehydrogenase. Milacemide was a reversible competitive inhibitor towards monoamine oxidase-A. The inhibitor constant (Ki) was 115 +/- 35 microM indicating a higher affinity than that towards monoamine oxidase-B, which was also competitively inhibited in the absence of enzyme-inhibitor preincubation (Ki = 331 +/- 185 microM). Determination of the formation of H2O2 and the aldehyde product of the oxidative cleavage of milacemide by purified monoamine oxidase-B from ox liver indicated that cleavage resulted solely in the formation of pentanal and glycinamide. There was no evidence for alternative cleavage to pentylamine and oxamaldehyde.
O'Brien
E M
EM
Department of Biochemistry, Trinity College, Dublin, Ireland.
Tipton
K F
KF
McCrodden
J M
JM
Youdim
M B
MB
D000081:Acetamides / Q000737:chemistry / Q000378:metabolism*; D000447:Aldehydes / Q000032:analysis; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000032:analysis; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats
D000081:Acetamides; D000447:Aldehydes; D000927:Anticonvulsants; D008996:Monoamine Oxidase Inhibitors; C039332:milacemide; C018556:glycine amide; C046012:pentanal; D008995:Monoamine Oxidase; D005998:Glycine