Wölfle D, Schmidt H, Jungermann K
Eur J Biochem. 1983 Oct 3;135(3):405-12. doi: 10.1111/j.1432-1033.1983.tb07667.x.
The influence of different oxygen concentrations (0% to 20%, v/v) on the main pathways of carbohydrate metabolism was studied in rat hepatocyte cultures. Cells resembling the periportal or the perivenous cell type were obtained after 48 h culture under different hormonal conditions; they are referred to as 'periportal' or 'perivenous', respectively. Using radiochemical techniques the metabolic rates of the two cell types were measured between 48 h and 50 h under different oxygen tensions. Standard physiological substrates of 5 mM glucose, 2 mM lactate and endogenous glycogen were used. In cells incubated under 4% O2, mimicking hepatovenous oxygen levels, compared to cells assayed under 13% O2, mimicking arterial levels, glycogen degradation to free glucose and to lactate was faster while glycogen synthesis was slower; glycolysis, from glucose to lactate, was faster and gluconeogenesis, from lactate to glucose, was only slightly slower. Under anoxic conditions glycogen breakdown was maximal and glycogen synthesis minimal; gluconeogenesis was also minimal, but glycolysis was not maximal, it reached its peak rate at 4% O2. CO2-formation increased up to 6% and then stayed essentially constant at higher O2 tensions. Net glycogen metabolism: in 'perivenous' cells net glycogen synthesis was observed above, net glycogen degradation below 4% O2. In 'periportal' cells, which had a very low glycogen content, net glycogen metabolism was very small. Net glucose metabolism: in 'perivenous' cells net glucose formation was only seen under anoxic conditions. Net glucose utilization was observed at about the same rate under all physiological O2 tensions. In 'periportal' cells net glucose formation increased clearly up to 6% O2 and then remained almost constant. Net lactate metabolism: in 'perivenous' cells net lactate formation occurred below, and net lactate utilization above, 6% O2. In 'periportal' cells a pronounced net lactate utilization was observed under all physiological O2 tensions. Net flow between glucose-6-phosphate and pyruvate was observed in the glycolytic direction in 'perivenous' and in the gluconeogenic direction in 'periportal' cells except under anoxic conditions. When O2 tensions were lowered, the percentage of 'futile cycling' was decreased in the 'perivenous', glycolytic hepatocytes; conversely, it was increased in the 'periportal', gluconeogenic hepatocytes. It is concluded that physiological oxygen concentrations modulate hepatic carbohydrate metabolism and that they contribute further to the proposed metabolic differences between periportal and perivenous cells in vivo.
在大鼠肝细胞培养物中研究了不同氧浓度（0%至20%，v/v）对碳水化合物代谢主要途径的影响。在不同激素条件下培养48小时后，获得了类似门静脉周围或肝静脉周围细胞类型的细胞；它们分别被称为“门静脉周围”或“肝静脉周围”细胞。使用放射化学技术在不同氧张力下测量了两种细胞类型在48小时至50小时之间的代谢率。使用了5 mM葡萄糖、2 mM乳酸和内源性糖原等标准生理底物。与在模拟动脉水平的13% O₂ 下测定的细胞相比，在模拟肝静脉氧水平的4% O₂ 下孵育的细胞中，糖原降解为游离葡萄糖和乳酸的速度更快，而糖原合成速度较慢；从葡萄糖到乳酸的糖酵解速度更快，从乳酸到葡萄糖的糖异生仅略慢。在缺氧条件下，糖原分解最大，糖原合成最小；糖异生也最小，但糖酵解不是最大，它在4% O₂ 时达到峰值速率。CO₂ 生成增加至6%，然后在较高的O₂ 张力下基本保持恒定。净糖原代谢：在“肝静脉周围”细胞中，在4% O₂ 以上观察到净糖原合成，在4% O₂ 以下观察到净糖原降解。在糖原含量非常低的“门静脉周围”细胞中，净糖原代谢非常小。净葡萄糖代谢：在“肝静脉周围”细胞中，仅在缺氧条件下观察到净葡萄糖生成。在所有生理O₂ 张力下，净葡萄糖利用率以大致相同的速率观察到。在“门静脉周围”细胞中，净葡萄糖生成在O₂ 浓度达到6%之前明显增加，然后几乎保持恒定。净乳酸代谢：在“肝静脉周围”细胞中，在6% O₂ 以下发生净乳酸生成，在6% O₂ 以上发生净乳酸利用。在“门静脉周围”细胞中，在所有生理O₂ 张力下均观察到明显的净乳酸利用。除缺氧条件外，在“肝静脉周围”细胞中观察到葡萄糖-6-磷酸和丙酮酸之间的净流量沿糖酵解方向，在“门静脉周围”细胞中沿糖异生方向。当O₂ 张力降低时，“肝静脉周围”糖酵解肝细胞中“无效循环”的百分比降低；相反，在“门静脉周围”糖异生肝细胞中增加。结论是生理氧浓度调节肝脏碳水化合物代谢，并且它们进一步促成了体内门静脉周围和肝静脉周围细胞之间提出的代谢差异。
