Gibson G E, Jope R, Blass J P
Biochem J. 1975 Apr;148(1):17-23. doi: 10.1042/bj1480017.
The relation between pyruvate utilization and acetylcholine synthesis was investigated in minces of adult rat brain. The flux of pyruvate to acetylcholine was less than 1% of that to CO2; nevertheless, a number of agents which inhibited conversion of [1-14C]-pyruvate or [2-14C]pyruvate into 14CO2 were associated with corresponding decreases in the conversion of [2-14C]pyruvate into acetylcholine. The amount of acetylcholine produced by minces of whole rat brain, measured by g.l.c.-mass spectrometry, decreased similarly. Among the inhibitory compounds tested were 3-bromopyruvate, an irreversible inhibitor of pyruvate dehydrogenase; 2-oxobutyrate, a competitive inhibitor of pyruvate dehydrogenase; other 2-oxo acids; and amobarbital and pentobarbital. Linear-regression equations relating CO2 production to acetylcholine synthesis gave correlation coefficients of 0.89-0.93 for the combined observations. The inhibition of acetylcholine synthesis could not be attributed to inhibition of choline acetyltransferase. Incorporation of [2-14C]pyruvate into lipids, proteins and nucleic acids was effected less than that into acetylcholine. Under these experimental conditions, it was shown that pyruvate utilization can limit acetylcholine synthesis.
在成年大鼠脑匀浆中研究了丙酮酸利用与乙酰胆碱合成之间的关系。丙酮酸转化为乙酰胆碱的通量不到其转化为二氧化碳通量的1%；然而，许多抑制[1-¹⁴C] - 丙酮酸或[2-¹⁴C] - 丙酮酸转化为¹⁴CO₂的试剂，与[2-¹⁴C] - 丙酮酸转化为乙酰胆碱的相应减少有关。通过气相色谱 - 质谱法测定，全大鼠脑匀浆产生的乙酰胆碱量也有类似减少。所测试的抑制性化合物包括丙酮酸脱氢酶的不可逆抑制剂3 - 溴丙酮酸；丙酮酸脱氢酶的竞争性抑制剂2 - 氧代丁酸；其他2 - 氧代酸；以及异戊巴比妥和戊巴比妥。将二氧化碳产生与乙酰胆碱合成相关联的线性回归方程，对综合观察结果给出的相关系数为0.89 - 0.93。乙酰胆碱合成的抑制不能归因于胆碱乙酰转移酶的抑制。[2-¹⁴C] - 丙酮酸掺入脂质、蛋白质和核酸的量比掺入乙酰胆碱的量少。在这些实验条件下，表明丙酮酸利用可以限制乙酰胆碱的合成。
