Larrabee M G
J Neurochem. 1983 May;40(5):1237-50. doi: 10.1111/j.1471-4159.1983.tb13562.x.
Uptake and output of lactate were measured in lumbar sympathetic chains excised from embryos of white leghorn chickens, 14-15 days old. The chains, typically containing 30-40 micrograms of protein, were incubated in Eagle's minimum essential medium containing bicarbonate buffer, 6-17 mM glucose, various concentrations of lactate, and either [U-14C]lactate, [1-14C]glucose, or [6-14C]glucose. The average rate of uptake of labeled lactate was measured with incubations of 5-6 h, starting with various external lactate concentrations. From these data the instantaneous relation between lactate uptake rate and concentration was deduced with a simple computerized model. The instantaneous uptake rate increased with the concentration according to a relation that fit the Michaelis-Menten equation, with Vmax = 360 mumol/g protein/h and Km = 4.8 mM. Substantial fractions of the lactate carbon were recovered from tissue constituents and in several nonvolatile products in the medium, as well as in CO2. Glucose uptake averaged about 108 mumol/g protein/h and did not vary greatly with external lactate concentration, although the metabolic partitioning of glucose carbon was considerably affected. Regardless of initial concentration, the lactate concentration in the medium tended to change towards approximately 0.6 mM, showing that uptake equaled output at this level, with rates at about 40 mumol/g protein/h. With the steady-state concentration of 0.6 mM lactate, about 20% of the glucose carbon was shunted out into the medium before it was reabsorbed and metabolized into various products. Lactate uptakes by neuronal and nonneuronal cultures prepared from the ganglia did not differ consistently from one another or from uptake by undissociated ganglia. The neuronal cultures tended to oxidize a greater fraction of the consumed lactate to CO2 and to convert a smaller fraction of the lactate to products in the medium than did the nonneuronal cultures. Computer modeling, using known parameters for blood-brain transport of lactate in the adult rat and data on uptake by the ganglia, suggests that lactate may supply substantial fuel to the brain, even in the presence of abundant glucose, when the lactate concentration in the blood is raised to levels commonly observed in exercising humans, such as 10-20 mM. This is in agreement with the findings of several investigators in hypoglycemic humans and in animals with intermediate blood lactate concentrations.
对14 - 15日龄白来航鸡胚胎切除的腰交感神经链中的乳酸摄取和输出进行了测量。这些神经链通常含有30 - 40微克蛋白质,在含有碳酸氢盐缓冲液、6 - 17毫摩尔葡萄糖、各种浓度乳酸以及[U - 14C]乳酸、[1 - 14C]葡萄糖或[6 - 14C]葡萄糖的伊格尔最低限度基本培养基中孵育。从不同的外部乳酸浓度开始,通过5 - 6小时的孵育来测量标记乳酸的平均摄取速率。根据这些数据,用一个简单的计算机模型推导出乳酸摄取速率与浓度之间的瞬时关系。瞬时摄取速率根据符合米氏方程的关系随浓度增加,Vmax = 360微摩尔/克蛋白质/小时,Km = 4.8毫摩尔。乳酸碳的相当一部分从组织成分以及培养基中的几种非挥发性产物以及二氧化碳中回收。葡萄糖摄取平均约为108微摩尔/克蛋白质/小时,并且随外部乳酸浓度变化不大,尽管葡萄糖碳的代谢分配受到相当大的影响。无论初始浓度如何,培养基中的乳酸浓度倾向于朝着约0.6毫摩尔变化,表明在此水平摄取量等于输出量,速率约为40微摩尔/克蛋白质/小时。在乳酸稳态浓度为0.6毫摩尔时,约20%的葡萄糖碳在被重新吸收并代谢为各种产物之前被分流到培养基中。从神经节制备的神经元和非神经元培养物对乳酸的摄取彼此之间以及与未分离的神经节的摄取没有一致的差异。与非神经元培养物相比,神经元培养物倾向于将消耗的乳酸中更大比例氧化为二氧化碳,并将更小比例的乳酸转化为培养基中的产物。使用成年大鼠乳酸血脑转运的已知参数和神经节摄取数据进行的计算机建模表明,当血液中乳酸浓度升高到运动人类中常见的水平,如10 - 20毫摩尔时,即使在有丰富葡萄糖存在的情况下,乳酸也可能为大脑提供大量燃料。这与几位研究人员在低血糖人类和血液乳酸浓度中等的动物中的发现一致。