分离的肝细胞中甘氨酸裂解系统的通量：胰高血糖素、环磷酸腺苷和钙的作用。

Flux through glycine cleavage system in isolated hepatocytes: effects of glucagon, cAMP, and calcium.

作者信息

Jois M, Hall B, Collett V M, Brosnan J T

机构信息

Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.

出版信息

Biochem Cell Biol. 1990 Feb;68(2):543-6. doi: 10.1139/o90-077.

DOI:10.1139/o90-077

PMID:2160835

Abstract

The hepatic glycine cleavage system (GCS) is the principal route for the metabolism of glycine in mammals. Flux through the GCS in isolated rat hepatocytes was stimulated by about 100% by glucagon (10(-7) M), forskolin (10(-4) M), and dibutyryl cAMP (10(-4) M). The stimulation of flux through the GCS by these agents was accompanied by marked elevation of cellular cAMP levels. A significant correlation was observed between increased cellular cAMP levels induced by glucagon and stimulation of flux through the GCS by glucagon. Exclusion of calcium from the incubation medium reduced the basal flux by 38%, but did not affect the degree of stimulation of flux through the GCS by glucagon. A single intraperitoneal injection of glucagon to rats prior to isolation of hepatocytes resulted in a 76% stimulation of flux through the GCS. These hepatocytes with stimulated flux through the GCS showed reduced sensitivity for further stimulation by glucagon. Half-maximal stimulation of flux through the GCS occurred at 3.8 +/- 1.1 and 8.5 +/- 1.4 nM glucagon in hepatocytes isolated from control and glucagon-injected rats, respectively. We conclude that cAMP is involved in the regulation of flux through the GCS by glucagon.

摘要

肝脏甘氨酸裂解系统（GCS）是哺乳动物中甘氨酸代谢的主要途径。在分离的大鼠肝细胞中，胰高血糖素（10⁻⁷ M）、福斯高林（10⁻⁴ M）和二丁酰环磷腺苷（10⁻⁴ M）可使通过GCS的通量增加约100%。这些物质对GCS通量的刺激伴随着细胞内cAMP水平的显著升高。观察到胰高血糖素诱导的细胞内cAMP水平升高与胰高血糖素对GCS通量的刺激之间存在显著相关性。孵育培养基中去除钙可使基础通量降低38%，但不影响胰高血糖素对GCS通量的刺激程度。在分离肝细胞之前，给大鼠腹腔注射一次胰高血糖素，可使通过GCS的通量增加76%。这些GCS通量受到刺激的肝细胞对胰高血糖素的进一步刺激表现出敏感性降低。从对照大鼠和注射胰高血糖素的大鼠分离的肝细胞中，GCS通量的半数最大刺激分别在3.8±1.1 nM和8.5±1.4 nM胰高血糖素时出现。我们得出结论，cAMP参与了胰高血糖素对GCS通量的调节。