Deshmukh D R, Ghole V S, Marescau B, De Deyn P P
Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
Arch Physiol Biochem. 1997 Feb;105(1):32-7. doi: 10.1076/apab.105.1.32.13144.
The effect of endotoxemia on the levels of amino acids, nitrates, nitrites and guanidino compounds was investigated. Plasma levels of nitrate and nitrite were significantly increased indicating increased production of nitric oxide during endotoxemia. Plasma concentrations of alanine, glutamine, leucine, methionine, phenylalanine, proline and taurine were also significantly elevated. These results indicate that endotoxin produces a hypercatabolic state. The plasma concentration of arginine was significantly decreased whereas the concentrations of ornithine and urea, the catabolites of arginine were increased. Decreased plasma arginine coupled with increased plasma ornithine and urea indicate that arginine catabolism is increased and arginine synthesis is decreased during endotoxemia. Plasma levels of creatine, creatinine, guanidine and guanidinosuccinic acid were significantly elevated whereas homoarginine levels were significantly decreased. Nitric oxide synthase utilizes arginine as well as homoarginine as substrates. The decreased concentration of both substrates may be related to alterations in nitric oxide synthase activity during endotoxemia. These results suggest that in addition to nitric oxide, other catabolites of arginine such as guanidino compounds may be important in the pathophysiology of endotoxemia. Because of the marked increase in guanidinosuccinic acid, a known uremic toxin, we speculate that guanidinosuccinic acid may be important in the pathophysiology of endotoxemia.
研究了内毒素血症对氨基酸、硝酸盐、亚硝酸盐和胍基化合物水平的影响。血浆硝酸盐和亚硝酸盐水平显著升高,表明内毒素血症期间一氧化氮生成增加。血浆丙氨酸、谷氨酰胺、亮氨酸、蛋氨酸、苯丙氨酸、脯氨酸和牛磺酸的浓度也显著升高。这些结果表明内毒素会导致高分解代谢状态。精氨酸的血浆浓度显著降低,而精氨酸的分解代谢产物鸟氨酸和尿素的浓度升高。血浆精氨酸降低,同时血浆鸟氨酸和尿素升高,表明内毒素血症期间精氨酸分解代谢增加而精氨酸合成减少。血浆肌酸、肌酐、胍和胍基琥珀酸水平显著升高,而高精氨酸水平显著降低。一氧化氮合酶利用精氨酸以及高精氨酸作为底物。两种底物浓度的降低可能与内毒素血症期间一氧化氮合酶活性的改变有关。这些结果表明,除了一氧化氮外,精氨酸的其他分解代谢产物如胍基化合物在内毒素血症的病理生理学中可能也很重要。由于已知的尿毒症毒素胍基琥珀酸显著增加,我们推测胍基琥珀酸在内毒素血症的病理生理学中可能很重要。