Tabuchi S, Gotoh T, Miyanaka K, Tomita K, Mori M
Department of Molecular Genetics, Kumamoto University School of Medicine, Kumamoto, 860-0811, Japan.
Biochem Biophys Res Commun. 2000 Feb 5;268(1):221-4. doi: 10.1006/bbrc.2000.2105.
Arginine is an intermediate of the urea cycle in the liver. It is synthesized by the first four enzymes of the cycle, carbamylphosphate synthetase I, ornithine transcarbamylase, argininosuccinate synthetase, and argininosuccinate lyase, and is hydrolyzed to urea and ornithine by arginase I, forming the cycle. In endotoxemia shock, inducible nitric oxide (NO) synthase (iNOS) is induced in hepatocytes and arginine is utilized for NO production. Regulation of the genes for iNOS and the urea cycle enzymes was studied using lipopolysaccharide (LPS)-treated rat livers. When rats were injected intraperitoneally with LPS, iNOS mRNA was markedly induced. Cationic amino acid transporter-2 and C/EBPbeta mRNAs were also highly increased. In contrast, mRNAs for all the urea cycle enzymes except ornithine transcarbamylase were gradually decreased and reached 16-28% of controls at 12 h. However, all these enzymes remained unchanged at protein level up to 24 h. In light of these results, we suggest that synthesis of urea cycle enzymes is downregulated and that the protein synthetic capacity is directed to synthesis of proteins required for defense against endotoxemia.
精氨酸是肝脏中尿素循环的中间产物。它由该循环的前四种酶合成，即氨基甲酰磷酸合成酶I、鸟氨酸转氨甲酰酶、精氨琥珀酸合成酶和精氨琥珀酸裂解酶，并通过精氨酸酶I水解为尿素和鸟氨酸，从而形成循环。在内毒素血症休克中，肝细胞中诱导型一氧化氮（NO）合酶（iNOS）被诱导，精氨酸用于生成NO。使用脂多糖（LPS）处理的大鼠肝脏研究了iNOS和尿素循环酶基因的调控。当大鼠腹腔注射LPS时，iNOS mRNA被显著诱导。阳离子氨基酸转运体-2和C/EBPβ mRNA也高度增加。相反，除鸟氨酸转氨甲酰酶外，所有尿素循环酶的mRNA逐渐减少，在12小时时降至对照组的16%-28%。然而，直到24小时，所有这些酶的蛋白质水平均保持不变。鉴于这些结果，我们认为尿素循环酶的合成受到下调作用，并且蛋白质合成能力被导向合成抵御内毒素血症所需的蛋白质。
