INFLUENCE OF MOLECULAR-STRUCTURE ON HALF-LIFE AND HYDROLYSIS OF DIPEPTIDES IN PLASMA - IMPORTANCE OF GLYCINE AS N-TERMINAL AMINO-ACID RESIDUE
INFLUENCE OF MOLECULAR-STRUCTURE ON HALF-LIFE AND HYDROLYSIS OF DIPEPTIDES IN PLASMA - IMPORTANCE OF GLYCINE AS N-TERMINAL AMINO-ACID RESIDUE
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DOI：
10.1016/0026-0495(86)90224-6
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发表时间：
1986-09-01
影响因子：
9.8
通讯作者：
MORSE, EL
中科院分区：
文献类型：
--
作者：
ADIBI, SA;PALEOS, GA;MORSE, EL
为了研究分子结构对血浆中二肽消失和代谢的影响，我们给大鼠静脉注射单个二肽，并在注射后不同时间间隔测量血浆、组织和尿液中二肽和氨基酸的浓度。此外，还研究了血浆水解酶对单个二肽的活性。Ala-Leu、Ala-Tyr和Ala-Gln的半衰期比甘氨酸取代丙氨酸的二肽短。此外，丙氨酰组血浆中亮氨酸、酪氨酸和谷氨酰胺浓度的增加以及血浆酶对二肽的水解率远高于甘氨酰组。事实上，Ala-Leu在提高血浆亮氨酸浓度方面表现得像相应的游离氨基酸的混合物，而Gly-Leu则没有。以Leu-Gly和Leu-Ala为底物时，血浆半衰期和水解率均无显著差异，但两者在血浆中的水解率均较快。与Gly-Leu相比，Phe-Leu和Arg-Leu在血浆中的半衰期更短，水解率更高。另一方面，Asp-Leu的血浆水解速率比Gly-Leu慢，但其在尿中的排泄量却比Gly-Leu大得多。与Gly-Leu和Ala-Leu相比，Gly-Pro在肝脏、肌肉，尤其是肾脏的细胞内检测到。事实上，肾脏中Gly-Pro的细胞内浓度等于或大于血浆中Gly-Pro的浓度。注射单个二肽后，肾脏细胞内氨基酸浓度的增加明显大于肝脏或肌肉。数据表明，n端甘氨酸通常优于其他氨基酸，可最大限度地减少血浆中二肽的水解，而不影响肾脏等组织的同化，这在循环二肽的摄取中起主要作用。
To investigate the effect of molecular structure on plasma disappearance and metabolism of dipeptides, rats were injected intravenously with individual dipeptides, and at various intervals after injection, dipeptide and amino acid concentrations were measured in plasma, tissues, and urine. In addition, plasma hydrolase activity against individual dipeptides was investigated. The half-lives of Ala-Leu, Ala-Tyr, and Ala-Gln were shorter than those of dipeptides with glycine substituting for alanine. Furthermore, the increases in plasma concentrations of leucine, tyrosine, and glutamine and rates of dipeptide hydrolysis by plasma enzymes were far greater with alanyl than glycyl dipeptides. In fact, Ala-Leu behaved like a mixture of corresponding free amino acids in raising the plasma concentration of leucine while Gly-Leu did not. There was no significant difference in either plasma half-life or hydrolysis when Leu-Gly and Leu-Ala were used as substrates, but both had rapid rates of hydrolysis in plasma. In comparison with Gly-Leu, Phe-Leu and Arg-Leu had shorter half-lives and greater rates of hydrolysis in plasma. On the other hand, Asp-Leu had a slower rate of plasma hydrolysis than Gly-Leu, but its excretion in the urine was much greater than that of Gly-Leu. In contrast to Gly-Leu and Ala-Leu, Gly-Pro was detected intracellularly in liver, muscle, and particularly, kidney. In fact, the intracellular concentration of Gly-Pro in kidney was either equal to or greater than Gly-Pro concentration in plasma. Increases in intracellular amino acid concentration after injection of individual dipeptides were considerably greater in the kidney than in either liver or muscle. The data suggest that glycine in the N-terminus is generally superior to other amino acids for minimizing dipeptide hydrolysis in plasma without compromising assimilation by tissues such as kidney, which plays a major role in the uptake of circulating dipeptides.