Jois M, Hall B, Fewer K, Brosnan J T
Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
J Biol Chem. 1989 Feb 25;264(6):3347-51.
Glucagon stimulates 14CO2 production from [1-14C] glycine by isolated rat hepatocytes. Maximal stimulation (70%) of decarboxylation of glycine by hepatocytes was achieved when the concentration of glucagon in the medium reached 10 nM; half-maximal stimulation occurred at a concentration of about 2 nM. A lag period of 10 min was observed before the stimulation could be measured. Inclusion of beta-hydroxybutyrate (10 mM) or acetoacetate (10 mM) did not affect the magnitude of stimulation suggesting that the effects of glucagon were independent of mitochondrial redox state. Glucagon did not affect either the concentration or specific activity of intracellular glycine, thus excluding the possibilities that altered concentration or specific activity of intracellular glycine contributes to the observed stimulation. The stimulation of decarboxylation of glycine by glucagon was further studied by monitoring 14CO2 production from [1-14C]glycine by mitochondria isolated from rats previously injected with glucagon. Glycine decarboxylation was significantly stimulated in the mitochondria isolated from the glucagon-injected rats. We suggest that glucagon is a major regulator of hepatic glycine metabolism through the glycine cleavage enzyme system and may be responsible for the increased hepatic glycine removal observed in animals fed high-protein diets.
胰高血糖素可刺激离体大鼠肝细胞从[1-¹⁴C]甘氨酸产生¹⁴CO₂。当培养基中胰高血糖素浓度达到10 nM时，肝细胞对甘氨酸脱羧的刺激作用达到最大（70%）；半最大刺激浓度约为2 nM。在可测量到刺激作用之前观察到10分钟的延迟期。加入β-羟基丁酸（10 mM）或乙酰乙酸（10 mM）不影响刺激幅度，这表明胰高血糖素的作用与线粒体氧化还原状态无关。胰高血糖素既不影响细胞内甘氨酸的浓度，也不影响其比活性，因此排除了细胞内甘氨酸浓度或比活性改变导致观察到的刺激作用的可能性。通过监测先前注射胰高血糖素的大鼠分离出的线粒体从[1-¹⁴C]甘氨酸产生¹⁴CO₂的情况，进一步研究了胰高血糖素对甘氨酸脱羧的刺激作用。从注射胰高血糖素的大鼠分离出的线粒体中，甘氨酸脱羧受到显著刺激。我们认为，胰高血糖素是通过甘氨酸裂解酶系统对肝脏甘氨酸代谢的主要调节因子，可能是导致高蛋白饮食喂养的动物肝脏中甘氨酸清除增加的原因。
