THE METABOLISM OF AMINOACETONE TO METHYLGLYOXAL BY SEMICARBAZIDE-SENSITIVE AMINE OXIDASE IN HUMAN UMBILICAL ARTERY

The aliphatic amine aminoacetone has been described previously as a product of mitochondrial metabolism of threonine and glycine. Here, aminoacetone is shown to be deaminated to methylglyoxal by supernatants obtained by low speed centrifugation (600 g/10 min) of human umbilical artery homogenates, and also by membrane fractions isolated by high speed centrifugation (105,000 g/60 min) of these supernatants. Metabolism of 100-mu-M aminoacetone was completely inhibited by 1 mM propargylamine and MDL 72145, drugs which are capable of inhibiting the membrane-bound semicarbazide-sensitive amine oxidase (SSAO) activity found in vascular smooth muscle cells, whereas 1 mM pargyline and deprenyl which are inhibitors of monoamine oxidase, were without inhibitory effect. Estimated kinetic constants (at pH 7.8) for aminoacetone metabolism were K(m) = 92-mu-M; V(max) = 270 nmol/hr/mg protein. In addition, aminoacetone was a competitive inhibitor (K(i) = 83-mu-M and 128-mu-M in low speed supernatants and high speed membrane fractions, respectively) of [C-14]benzylamine metabolism by SSAO in this tissue. Aminoacetone would appear to be an endogenously occurring amine with a K(m) for metabolism by SSAO far lower than other aliphatic and aromatic biogenic amines examined previously as potential physiological substrates for the human vascular enzyme and possible implications of this are discussed.