The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine oxidase

Sam Kaitaniemi; Heli Elovaara; Kirsi Grön; Heidi Kidron; Janne Liukkonen; Tiina Salminen; Marko Salmi; Sirpa Jalkanen; Kati Elima

doi:10.1007/s00018-009-0076-5

The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine oxidase

Cell Mol Life Sci. 2009 Aug;66(16):2743-57. doi: 10.1007/s00018-009-0076-5. Epub 2009 Jul 9.

Authors

Sam Kaitaniemi¹, Heli Elovaara, Kirsi Grön, Heidi Kidron, Janne Liukkonen, Tiina Salminen, Marko Salmi, Sirpa Jalkanen, Kati Elima

Affiliation

¹ MediCity Research Laboratory, University of Turku, and National Institute for Health and Welfare, Tykistökatu 6, 20520 Turku, Finland.

PMID: 19588076
DOI: 10.1007/s00018-009-0076-5

Abstract

Semicarbazide-sensitive amine oxidases (SSAOs) catalyze oxidative deamination of primary amines, but the true physiological function of these enzymes is still poorly understood. Here, we have studied the functional and structural characteristics of a human cell-surface SSAO, AOC2, which is homologous to the better characterized family member, AOC3. The preferred in vitro substrates of AOC2 were found to be 2-phenylethylamine, tryptamine and p-tyramine instead of methylamine and benzylamine, the favored substrates of AOC3. Molecular modeling suggested structural differences between AOC2 and AOC3, which provide AOC2 with the capability to use the larger monoamines as substrates. Even though AOC2 mRNA was expressed in many tissues, the only tissues with detectable AOC2-like enzyme activity were found in the eye. Characterization of AOC2 will help in evaluating the contribution of this enzyme to the pathological processes attributed to the SSAO activity and in designing specific inhibitors for the individual members of the SSAO family.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Amine Oxidase (Copper-Containing) / chemistry
Amine Oxidase (Copper-Containing) / metabolism*
Amine Oxidase (Copper-Containing) / physiology
Cell Adhesion Molecules / chemistry
Cell Adhesion Molecules / metabolism
Cell Adhesion Molecules / physiology
Cloning, Molecular
Dimerization
Eye / metabolism
Eye Proteins / chemistry
Eye Proteins / metabolism*
Eye Proteins / physiology
Humans
Kinetics
Models, Molecular
Mutagenesis, Site-Directed
Oxidoreductases Acting on CH-NH Group Donors / chemistry
Oxidoreductases Acting on CH-NH Group Donors / metabolism*
Oxidoreductases Acting on CH-NH Group Donors / physiology
Phenethylamines / metabolism
Protein Structure, Tertiary
RNA, Messenger / metabolism
Substrate Specificity
Tryptamines / metabolism
Tyramine / metabolism

Substances

Cell Adhesion Molecules
Eye Proteins
Phenethylamines
RNA, Messenger
Tryptamines
phenethylamine
tryptamine
AOC2 protein, human
AOC3 protein, human
Amine Oxidase (Copper-Containing)
Oxidoreductases Acting on CH-NH Group Donors
Tyramine