ホルモンのcarbamylationとその生物活性に及ぼす影響

概要

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It has been demonstrated that the binding of cyanic acid, formed from urea which is increased in renal failure, to hemoglobin (Hb) results in the formation of HbAi. The combination of Hb and cyanic acid is called carbamylation, a nonspecific reaction between protein and cyanic acid. It is theoretically considered that like glycation, carbamylation may occur between cyanic acid and not only Hb but also various peptides and proteins. In the present study, hormones were subjected to carbamylation, and the effects of carbamylation on the biological activity of the hormones, i.e. 3, 5, 3'-L-triiodothyronine (T3) and insulin, were investigated. Carbamylated T3 and carbamylated insulin were synthesized in Vitro, using KCNO. The carbamylated hormones were isolated by high-performance liquid chromatography (HPLC). The biological activities of carbamylated T3 and carbamylated insulin were assayed by employing the metamorphosis of tadpoles (Rana nigrornaculata) and the glucose oxidation of fat cells or the receptor binding capacity of rat hepatocytes, respectively. The biological activity of carbamylated T3 was less than about 1/13 of that of T3, and the binding activity of carbamylated insulin was 1/5 of that of insulin. Therefore, carbamylation of hormones may be an important factor in the analysis of clinical conditions, especially the endocrine condition in renal failure.