Semicarbazide-sensitive amine oxidase. Its physiological significance*
K. Magyar1,#, Z. Mészáros1, and P. Mátyus2
1Department of Pharmacodynamics and 2Department of
Organic Chemistry, Faculty of Pharmacy, Semmelweis University, Budapest,
Hungary
Abstract: Although the existence of plasma- and tissue-bound
semicarbazide-sensitive amine oxidases (SSAOs) has been recognized earlier,
the physiological relevance of the enzyme still remains uncertain. Recent
data suggest that elevated serum SSAO activity might cause endothelial
injury. Formation of cytotoxic metabolites (e.g., formaldehyde) and
increased oxidative stress might lead to initiation or progression of
atherosclerosis. Significant positive correlation was found between
serum SSAO activity and severity of atherosclerosis, and diabetic macrovascular
complications. Effective and selective inhibitors of human SSAO might
exert cytoprotective effect on endothelial cells. Compounds, having
similar structure to mexiletine, were synthesized and studied relating
to SSAO activity. The reference substrate was MDL-72974A. Unfortunately,
our new compounds did not reach the potency of the reference substance
using human serum samples. In conclusion, we suppose that vascular and
soluble SSAO enzymes might have different inhibitor sensitivity. Further
studies are required to determine whether the soluble or vascular isoform
of SSAO will be the main therapeutic target in the future.
*Plenary lecture presented at the Hungarian-German-Italian-Polish
Joint Meeting on Medicinal Chemistry, Budapest, Hungary, 2 6 September
2001. Other presentations are published in this issue, pp.
1387-1509.
# Corresponding author.
Back to Contents for access to full
text
Page last modified 29 November 2001.
Copyright © 2001 International Union of Pure and Applied Chemistry.
Questions or comments about IUPAC, please contact, the Secretariat.
Questions regarding the website, please contact web
manager.