AOC3
Amine oxidase, copper containing 3 (vascular adhesion protein 1), also known as semicarbazide-sensitive amine oxidase (SSAO, copper-containing amine:oxygen oxidoreductase), is an enzyme that in humans is encoded by the AOC3 gene.[1][2][3]
Function
Copper amine oxidases catalyze the oxidative conversion of amines to aldehydes in the presence of copper and quinone cofactor. The product is a major protein on the adipocyte plasma membrane. It has adhesive properties and also has functional monoamine oxidase activity.[3]
Like monoamine oxidase (MAO), SSAO can deaminate short-chain primary amines, but is insensitive to MAO inhibitors. Semicarbazide inhibits the enzyme, in addition to other hydrazines, hydroxylamine and propargylamine. However, hydrazines are weak inhibitors and stronger inhibitors have been developed.
SSAO is found in the smooth muscle of blood vessels and various other tissues. The physiological function of SSAO is not well understood. Development of blood vessels, lipolysis regulation, and detoxication are suggested. It may function as a scavenger enzyme to assist MAO. However, the oxidation process generates harmful products that may be involved in causing atherosclerosis and vascular damage in diabetes. Elevation of SSAO activity is observed in atherosclerosis, diabetes mellitus, obesity, carotid plaque cases and varicosities.
There are SSAO inhibitors in development.[4][5]
Clinical relevance
Semicarbazide-cadmium therapy has been used to alleviate the symptoms of cancers, but the APIs have significant toxicity.
References
- ↑ Zhang X, McIntire WS (November 1996). "Cloning and sequencing of a copper-containing, topa quinone-containing monoamine oxidase from human placenta". Gene 179 (2): 279–86. doi:10.1016/S0378-1119(96)00387-3. PMID 8972912.
- ↑ Smith DJ, Salmi M, Bono P, Hellman J, Leu T, Jalkanen S (July 1998). "Cloning of Vascular Adhesion Protein 1 Reveals a Novel Multifunctional Adhesion Molecule". J. Exp. Med. 188 (1): 17–27. doi:10.1084/jem.188.1.17. PMC 2525535. PMID 9653080.
- ↑ 3.0 3.1 "Entrez Gene: AOC3 amine oxidase, copper containing 3 (vascular adhesion protein 1)".
- ↑ O'Rourke AM, Wang EY, Miller A et al. (2008). "Anti-inflammatory effects of LJP 1586 [Z-3-fluoro-2-(4-methoxybenzyl)allylamine hydrochloride], an amine-based inhibitor of semicarbazide-sensitive amine oxidase activity". The Journal of Pharmacology and Experimental Therapeutics 324 (2): 867–75. doi:10.1124/jpet.107.131672. PMID 17993604.
- ↑ Wang EY, Gao H, Salter-Cid L et al. (2006). "Design, synthesis, and biological evaluation of semicarbazide-sensitive amine oxidase (SSAO) inhibitors with anti-inflammatory activity". Journal of Medical Chemistry 49 (7): 2166–73. doi:10.1021/jm050538l. PMID 16570912.
Further reading
- Lalor PF, Lai WK, Curbishley SM et al. (2006). "Human hepatic sinusoidal endothelial cells can be distinguished by expression of phenotypic markers related to their specialised functions in vivo". World J. Gastroenterol. 12 (34): 5429–39. PMID 17006978.
- Bustelo XR, Barbacid M (1992). "Tyrosine phosphorylation of the vav proto-oncogene product in activated B cells". Science 256 (5060): 1196–9. doi:10.1126/science.256.5060.1196. PMID 1375396.
- Andersson B, Wentland MA, Ricafrente JY et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
- Zhang X, McIntire WS (1997). "Cloning and sequencing of a copper-containing, topa quinone-containing monoamine oxidase from human placenta". Gene 179 (2): 279–86. doi:10.1016/S0378-1119(96)00387-3. PMID 8972912.
- Yu W, Andersson B, Worley KC et al. (1997). "Large-Scale Concatenation cDNA Sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
- Smith DJ, Salmi M, Bono P et al. (1998). "Cloning of Vascular Adhesion Protein 1 Reveals a Novel Multifunctional Adhesion Molecule". J. Exp. Med. 188 (1): 17–27. doi:10.1084/jem.188.1.17. PMC 2525535. PMID 9653080.
- Lalor PF, Edwards S, McNab G et al. (2002). "Vascular adhesion protein-1 mediates adhesion and transmigration of lymphocytes on human hepatic endothelial cells". J. Immunol. 169 (2): 983–92. doi:10.4049/jimmunol.169.2.983. PMID 12097405.
- Salmi M, Stolen C, Jousilahti P et al. (2003). "Insulin-Regulated Increase of Soluble Vascular Adhesion Protein-1 in Diabetes". Am. J. Pathol. 161 (6): 2255–62. doi:10.1016/S0002-9440(10)64501-4. PMC 1850919. PMID 12466139.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Singh B, Tschernig T, van Griensven M et al. (2003). "Expression of vascular adhesion protein-1 in normal and inflamed mice lungs and normal human lungs". Virchows Arch. 442 (5): 491–5. doi:10.1007/s00428-003-0802-6. PMID 12700900.
- Zhang Q, Mashima Y, Noda S et al. (2004). "Characterization of AOC2 gene encoding a copper-binding amine oxidase expressed specifically in retina". Gene 318: 45–53. doi:10.1016/S0378-1119(03)00753-4. PMID 14585497.
- Conklin DJ, Cowley HR, Wiechmann RJ et al. (2004). "Vasoactive effects of methylamine in isolated human blood vessels: role of semicarbazide-sensitive amine oxidase, formaldehyde, and hydrogen peroxide". Am. J. Physiol. Heart Circ. Physiol. 286 (2): H667–76. doi:10.1152/ajpheart.00690.2003. PMID 14715500.
- Olivé M, Unzeta M, Moreno D, Ferrer I (2004). "Overexpression of semicarbazide-sensitive amine oxidase in human myopathies". Muscle Nerve 29 (2): 261–6. doi:10.1002/mus.10550. PMID 14755492.
- Forster-Horváth C, Döme B, Paku S et al. (2005). "Loss of vascular adhesion protein-1 expression in intratumoral microvessels of human skin melanoma". Melanoma Res. 14 (2): 135–40. doi:10.1097/00008390-200404000-00010. PMID 15057044.
- Aboulaich N, Vainonen JP, Strålfors P, Vener AV (2005). "Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes". Biochem. J. 383 (Pt 2): 237–48. doi:10.1042/BJ20040647. PMC 1134064. PMID 15242332.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Boomsma F, Pedersen-Bjergaard U, Agerholm-Larsen B et al. (2005). "Association between plasma activities of semicarbazide-sensitive amine oxidase and angiotensin-converting enzyme in patients with type 1 diabetes mellitus". Diabetologia 48 (5): 1002–7. doi:10.1007/s00125-005-1716-4. PMID 15830186.
- Li HY, Lee WJ, Chen MJ, Chuang LM (2005). "Change in vascular adhesion protein-1 and metabolic phenotypes after vertical banded gastroplasty for morbid obesity". Obes. Res. 13 (5): 855–61. doi:10.1038/oby.2005.98. PMID 15919838.
- Airenne TT, Nymalm Y, Kidron H et al. (2005). "Crystal structure of the human vascular adhesion protein-1: Unique structural features with functional implications". Protein Sci. 14 (8): 1964–74. doi:10.1110/ps.051438105. PMC 2279308. PMID 16046623.
| |||||||||||||||
