Sapir D G, Owen O E, Pozefsky T, Walser M
J Clin Invest. 1974 Oct;54(4):974-80. doi: 10.1172/JCI107838.
11 normal obese subjects were fasted for 33 days. In five, who served as controls, urine urea nitrogen excretion remained constant for 2 wk thereafter. The other six were given seven daily infusions containing 6-8 mmol each of the alpha-keto-analogues of valine, leucine, isoleucine, phenylalanine, and methionine (as sodium salts) plus 3-4 mmol each of the remaining essential amino acids (lysine, threonine, tryptophan, and histidine). Rapid amination of the infused ketoacids occurred, as indicated by significant increases in plasma concentrations of valine, leucine, isoleucine, alloisoleucine, phenylalanine, and methionine. Glutamine, glycine, serine, glutamate, and taurine fell significantly. Blood glucose, ketone bodies, plasma free fatty acids, and serum immunoreactive insulin concentrations were unaltered. Urine urea nitrogen fell from 1.46 to 0.89 g/day on the last day of infusions; 5 days later it was still lower (0.63 g/day) and in two subjects studied for 9 and 17 days postinfusion it remained below preinfusion control values. Urine ammonia, creatinine, and uric acid were unaltered. Nitrogen balance became less negative during and after infusions. The results indicate that this mixture of essential amino acids and their keto-analogues facilitates nitrogen sparing during prolonged starvation, in part by conversion of the ketoacids to amino acids and in part by altering mechanisms of nitrogen conservation. The latter effect persists after the ketoacids are metabolized.
11名正常肥胖受试者禁食33天。其中5名作为对照组，此后2周尿尿素氮排泄保持恒定。另外6名受试者每天接受7次输注，每次输注含缬氨酸、亮氨酸、异亮氨酸、苯丙氨酸和蛋氨酸的α-酮类似物各6 - 8 mmol（钠盐形式），以及其余必需氨基酸（赖氨酸、苏氨酸、色氨酸和组氨酸）各3 - 4 mmol。输注的酮酸迅速发生氨基化，表现为血浆中缬氨酸、亮氨酸、异亮氨酸、别异亮氨酸、苯丙氨酸和蛋氨酸浓度显著升高。谷氨酰胺、甘氨酸、丝氨酸、谷氨酸和牛磺酸显著下降。血糖、酮体、血浆游离脂肪酸和血清免疫反应性胰岛素浓度未改变。输注最后一天尿尿素氮从1.46 g/天降至0.89 g/天；5天后仍较低（0.63 g/天），在输注后研究9天和17天的两名受试者中，其仍低于输注前对照值。尿氨、肌酐和尿酸未改变。输注期间及之后氮平衡的负值变小。结果表明，这种必需氨基酸及其酮类似物的混合物在长期饥饿期间有助于节约氮，部分是通过将酮酸转化为氨基酸，部分是通过改变氮保留机制。后一种作用在酮酸代谢后仍然存在。
