Physiological and pathological implications of semicarbazide-sensitive amine oxidase

Biochim Biophys Acta. 2003 Apr 11;1647(1-2):193-9. doi: 10.1016/s1570-9639(03)00101-8.

Abstract

Semicarbazide-sensitive amine oxidase (SSAO) catalyzes the deamination of primary amines. Such deamination has been shown capable of regulating glucose transport in adipose cells. It has been independently discovered that the primary structure of vascular adhesion protein-1 (VAP-1) is identical to SSAO. VAP-1 regulates leukocyte migration and is related to inflammation. Increased serum SSAO activities have been found in patients with diabetic mellitus, vascular disorders and Alzheimer's disease. The SSAO-catalyzed deamination of endogenous substrates, that is, methylamine and aminoacetone, led to production of toxic formaldehyde and methylglyoxal, hydrogen peroxide and ammonia, respectively. These highly reactive aldehydes have been shown to initiate protein cross-linkage, exacerbate advanced glycation of proteins and cause endothelial injury. Hydrogen peroxide contributes to oxidative stress. 14C-methylamine is converted to 14C-formaldehyde, which then forms labeled long-lasting protein adduct in rodents. Chronic methylamine treatment increased the excretion of malondialdehyde and microalbuminuria, and enhanced the formation of fatty streaks in C57BL/6 mice fed with an atherogenic diet. Treatment with selective SSAO inhibitor reduces atherogenesis in KKAy diabetic mice fed with high-cholesterol diet. Aminoguanidine, which blocks advanced glycation and reduces nephropathy in animals, is in fact more potent at inhibiting SSAO than its effect on glycation. It suggests that SSAO is involved in vascular disorders under certain pathological conditions. Although SSAO has been known for several decades, its physiological and pathological implications are just beginning to be recognized.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetone / analogs & derivatives*
  • Acetone / metabolism
  • Adipocytes / metabolism
  • Amine Oxidase (Copper-Containing) / blood
  • Amine Oxidase (Copper-Containing) / physiology*
  • Animals
  • Catalysis
  • Cell Adhesion Molecules / physiology
  • Deamination
  • Formaldehyde / toxicity
  • Glucose / metabolism
  • Humans
  • Hydrogen Peroxide / toxicity
  • Inflammation / etiology
  • Methylamines / metabolism
  • Oxidation-Reduction
  • Semicarbazides / pharmacology*

Substances

  • Cell Adhesion Molecules
  • Methylamines
  • Semicarbazides
  • Acetone
  • Formaldehyde
  • Hydrogen Peroxide
  • methylamine
  • AOC3 protein, human
  • Amine Oxidase (Copper-Containing)
  • Glucose
  • aminoacetone