Semicarbazide-sensitive amine oxidase. Its physiological significance

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.

Flaxseed protein-derived peptide fractions: Antioxidant properties and inhibition of lipopolysaccharide-induced nitric oxide production in murine macrophages

“…is the name of a group of enzymes ubiquitously distributed in plants and animals. Amongst its several physiological roles, it catalyses the oxidative deamination of various primary amines to produce their respective aldehydes, ammonia and H 2 O 2 (Göktürk et al, 2003;Magyar, Mészáros, & Mátyus, 2001;Stolen, Madanat, et al, 2004;Stolen, Yegutkin, et al, 2004). Methylamine and aminoacetone are well-known endogenous substrates for SSAO; their deamination products are potential cytotoxic agents and precursors of 0308-8146/$ -see front matter Ó 2009 Elsevier Ltd. All rights reserved.…”

“…doi:10.1016/j.foodchem.2009.02.046 advanced glycation end-products (AGEs) (Göktürk et al, 2003;Stolen, Madanat, et al, 2004;Stolen, Yegutkin, et al, 2004). Plasma level of SSAO has been reported to be elevated in disease conditions such as diabetes mellitus, atherosclerosis, cerebral infarction, liver cirrhosis and congestive heart failure (Boomsma, De Kam, Tjeerdsma, Van Den Meiracker, & Van Veldhuisen, 2000;Göktürk et al, 2003;Magyar et al, 2001;Stolen, Madanat, et al, 2004;Stolen, Yegutkin et al, 2004). The increased serum activity of SSAO has been associated with progression of vascular endothelial damages mediated by AGEs (Stolen, Yegutkin, et al, 2004).…”

“…The increased serum activity of SSAO has been associated with progression of vascular endothelial damages mediated by AGEs (Stolen, Yegutkin, et al, 2004). Based on these findings, it was proposed that inhibition of SSAO could reduce the damages observed in these disease conditions (Göktürk et al, 2003;Magyar et al, 2001); moreover, SSAO inhibitory activities have been reported for natural and synthetic compounds and biomaterials (Lin, Wang, Lu, Wu, & Hou, 2008;Liu, Wu, Liang, & Hou, 2007).…”

About pathochemical changes of the system of metabolic homeostasis in acute period of ischemic stroke

“…Отсут-ствие взаимосвязи увеличения концентрации МСМ и показателей тяжести течения заболевания могло быть обусловлено компенсаторной активностью систем био-трансформации эндотоксинов [14]. Один из метаболических механизмов фермента-тивной трансформации ксенобиотиков связан с усилением активности плазматиче-ской САО [17,18]. Неожиданным результатом оказалось участие САО в одном из метаболических путей образования МСМ в норме, что подтверждалось сильной положительной достоверной корреляционной связью, характерной для группы кон-троля: МСМ/ САО r s = + 0, 64, P<0.005.…”

“…Молекулярная масса эндогенных патогенов колеблется в широ-ких пределах, при этом большая часть токсинов принадлежит к МСМ [5,8,11,15,20]. Ферментативная биотрансформация эндотоксинов связана с реакциями окисления при помощи плазматической САО [17,18]. Определение клинической значимости серологических маркеров неспецифической эндогенной интоксикации, таких как уровень МСМ и МДА, а также активности фермента биотрансформации эндоток-синов -плазматической САО в остром периоде ишемического инсульта необходи-мо для выбора адекватной тактики лечения и оценки реабилитационного потенциа-ла больного.…”