Maddrey W C, Weber F L, Coulter A W, Chura C M, Chapanis N P, Walser M
Gastroenterology. 1976 Aug;71(2):190-5.
Keto analogues of five essential amino acids (valine, leucine, isoleucine, methionine, and phenylalanine) were given either parenterally or orally in varying proportions to 11 patients with portal-systemic encephalopathy and hyperammonemia. Plasma concentrations of amino acids corresponding to the infused analogues, including alloisoleucine, increased significantly after infusions. Plasma tyrosine and glycine, which were abnormally elevated in control samples, fell after the infusions. After one to five daily infusions, the ratio of essential to nonessential amino acids in fasting plasma was increased toward normal, suggesting improved protein nutrition. Arterial blood ammonia and glutamate did not change immediately after infusions, but a pronounced decrease in glutamine (42%) was observed. Eight nitrogen balance studies performed in 5 patients during 3 to 12 days of oral or intravenous keto acid therapy failed to show consistent improvement in balance as compared with control periods. After five courses of oral therapy there was again significant improvement in the ratio of essential to nonessential amino acids. No toxicity from keto analogue administration was found, and clinical improvement, as assessed by mental status and psychological testing occurred in 8 of 11 patients. These studies suggest keto analogues of essential amino acids are converted to the corresponding amino acids in patients with portal-systemic encephalopathy, and that such therapy may be of benefit.
将五种必需氨基酸（缬氨酸、亮氨酸、异亮氨酸、蛋氨酸和苯丙氨酸）的酮类似物以不同比例通过胃肠外或口服方式给予11例门体性脑病和高氨血症患者。输注后，与输注的类似物相对应的氨基酸（包括别异亮氨酸）的血浆浓度显著升高。对照样本中异常升高的血浆酪氨酸和甘氨酸在输注后下降。每日输注1至5次后，空腹血浆中必需氨基酸与非必需氨基酸的比例趋向正常，提示蛋白质营养状况改善。输注后动脉血氨和谷氨酸水平未立即改变，但观察到谷氨酰胺显著下降（42%）。在5例患者进行口服或静脉酮酸治疗的3至12天期间进行的8次氮平衡研究未能显示与对照期相比平衡有持续改善。经过五个疗程的口服治疗后，必需氨基酸与非必需氨基酸的比例再次显著改善。未发现酮类似物给药有毒性，11例患者中有8例经精神状态和心理测试评估有临床改善。这些研究表明，必需氨基酸的酮类似物在门体性脑病患者体内可转化为相应的氨基酸，且这种治疗可能有益。
