Castillo L, Sánchez M, Chapman T E, Ajami A, Burke J F, Young V R
Laboratory of Human Nutrition, Massachusetts Institute of Technology, Cambridge 02142.
Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6393-7. doi: 10.1073/pnas.91.14.6393.
We hypothesized recently that arginine homeostasis is achieved in humans largely by modulating the rate of arginine degradation. We have tested this hypothesis further by measuring in vivo the whole body rate of conversion of arginine to ornithine and ornithine oxidation in six healthy young adults. Subjects received for 6 days an L-amino acid-based diet supplying an arginine-rich or arginine-free intake and on day 7, following an overnight fast, an 8-h tracer protocol (first 3 h, fast state; next 5 h, fed state) was conducted; L-[guanidino-15N2; 5,5-2H]arginine and L-[5-13C]ornithine were given as primed, constant intravenous tracers; measurements of the abundances of various isotopologs of arginine, ornithine, and citrulline in plasma were made, and from these the various kinetic parameters of the metabolism of these amino acids were derived. Arginine and ornithine fluxes were significantly (P < 0.001) reduced in the fed state with arginine-free feeding. The rates of conversion (mumol.kg-1.h-1; mean +/- SD) of plasma arginine to ornithine for arginine-rich were 12.9 +/- 2.6 and 24.7 +/- 4.8 for fast and fed states. These values were 11.1 +/- 3.5 and 9.6 +/- 1.2 (P > 0.05 and P < 0.001), respectively, with an arginine-free diet. [13C]Ornithine oxidation was reduced (P < 0.001) by 46% during the fed state when the arginine-free diet was given. The findings strengthen our hypothesis that homeostasis of arginine metabolism in the human host depends importantly upon a regulation in the rate of arginine degradation with, perhaps, little involvement in the de novo net rate of arginine synthesis.
我们最近推测，人体中精氨酸的稳态主要是通过调节精氨酸的降解速率来实现的。我们通过测量6名健康年轻成年人体内精氨酸向鸟氨酸的全身转化率以及鸟氨酸氧化率，进一步验证了这一假设。受试者连续6天接受基于L-氨基酸的饮食，分别提供富含精氨酸或不含精氨酸的摄入量，在第7天，经过一夜禁食后，进行了一个8小时的示踪实验方案（前3小时，禁食状态；接下来5小时，进食状态）；给予L-[胍基-15N2；5,5-2H]精氨酸和L-[5-13C]鸟氨酸作为预充、持续静脉示踪剂；测量血浆中精氨酸、鸟氨酸和瓜氨酸各种同位素异构体的丰度，并由此得出这些氨基酸代谢的各种动力学参数。在无精氨酸喂养的进食状态下，精氨酸和鸟氨酸通量显著降低（P < 0.001）。富含精氨酸饮食时，血浆精氨酸向鸟氨酸的转化率（μmol·kg-1·h-1；平均值±标准差）在禁食和进食状态下分别为12.9±2.6和24.7±4.8。无精氨酸饮食时，这些值分别为11.±3.5和9.6±1.2（P > 0.05和P < 0.001）。给予无精氨酸饮食时，进食状态下[13C]鸟氨酸氧化率降低（P < 0.001）46%。这些发现强化了我们的假设，即人类宿主中精氨酸代谢的稳态主要依赖于精氨酸降解速率的调节，而精氨酸从头合成的净速率可能参与较少。
