分离肝细胞中尿素生成与糖异生之间的相互关系。阴离子转运的作用及对能量的竞争。

Interrelations between ureogenesis and gluconeogenesis in isolated hepatocytes. The role of antion transport and the competition for energy.

Wojtczak A B, Wałajtys-Rode E I, Geelen M J

Biochem J. 1978 Feb 15;170(2):379-385. doi: 10.1042/bj1700379.

Abstract

Glucose synthesis from lactate plus pyruvate and from lactate plus alanine was measured in the presence or absence of 1mM-oleate or 2mM-octanoate at low (2mM) or high (8mM) concentrations of NH4Cl. 2. Both fatty acids alone or with 2mM-NH4Cl doubled glucose production from lactate plus pyruvate. Glucose synthesis from lactate plus alanine, in the presence of oleate, was decreased 16% by 2mM-NH4Cl. 3. In the presence of fatty acids, 8mM-NH4Cl decreased gluconeogenesis by 60-65% from both lactate plus pyruvate and lactate plus alanine. This inhibition was correlated with a high accumulation of aspartate and a drastic decrease in 2-oxoglutarate and malate in the cells. 4. In the presence of 2mM- or 8 mM-NH4Cl, oleate and glucogenic precursors, the addition of 2.5mM-ornithine stimulated urea synthesis. 5. This was paralleled by a decrease of 16% in glucose synthesis from lactate plus pyruvate in the presence of 2mM-NH4Cl and had no effect at 8mM-NH4Cl. In the system producing glucose from lactate plus alanine, ornithine completely reversed the inhibition caused by 2mM-NH4Cl and only partly that by 8mM-NH4Cl. 6. Gluconeogenesis from pyruvate was also inhibited by 2mM-NH4Cl in the presence of oleate or ethanol. This way due to the decrease of malate, which is the C4 precursor of glucose in this system. 7. The limitation of gluconeogenesis by 2-oxoglutarate and malate concentrations in the liver cell and the competition for energy between glucose and urea synthesis is discussed.

摘要

在低（2mM）或高（8mM）浓度的氯化铵存在或不存在的情况下，测定了从乳酸加丙酮酸以及从乳酸加丙氨酸合成葡萄糖的情况，同时还测定了在存在1mM油酸或2mM辛酸的情况下的合成情况。2. 单独的两种脂肪酸或与2mM氯化铵一起，使从乳酸加丙酮酸合成葡萄糖的量增加了一倍。在油酸存在的情况下，2mM氯化铵使从乳酸加丙氨酸合成葡萄糖的量减少了16%。3. 在脂肪酸存在的情况下，8mM氯化铵使从乳酸加丙酮酸和从乳酸加丙氨酸的糖异生作用分别降低了60 - 65%。这种抑制作用与细胞中天冬氨酸的大量积累以及2-氧代戊二酸和苹果酸的急剧减少相关。4. 在存在2mM或8mM氯化铵、油酸和生糖前体的情况下，添加2.5mM鸟氨酸刺激了尿素合成。5. 在2mM氯化铵存在的情况下，这伴随着从乳酸加丙酮酸合成葡萄糖的量减少了16%，而在8mM氯化铵存在时则没有影响。在从乳酸加丙氨酸生成葡萄糖的系统中，鸟氨酸完全逆转了2mM氯化铵引起的抑制作用，而对8mM氯化铵引起的抑制作用仅部分逆转。6. 在油酸或乙醇存在的情况下，2mM氯化铵也抑制了从丙酮酸的糖异生作用。这是由于苹果酸减少所致，而苹果酸是该系统中葡萄糖的C4前体。7. 讨论了肝细胞中2-氧代戊二酸和苹果酸浓度对糖异生作用的限制以及葡萄糖和尿素合成之间的能量竞争。