Howland R D, Vyas I L, Lowndes H E, Argentieri T M
Brain Res. 1980 Nov 24;202(1):131-42.
The in vitro effects of the neurotoxic compounds, acrylamide and 2,5-hexanedione, on several glycolytic enzymes including enolase, phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and lactic dehydrogenase (LDH) were studied in rat brain. A differential sensitivity of the enzymes to the inhibitory effects of the neurotoxins was observed. The order of increasing sensitivity to 2,5-hexanedione was enolase -- GAPDH -- PFK and to acrylamide the order was PFK -- enolase -- GAPDH. Neither neurotoxin inhibited LDH. The inhibition of enolase by acrylamide exhibited a mixed type pattern in double reciprocal plots. The inhibition could be completely reversed by dialysis indicating that it did not involve covalent bond formation. In the presence of dithiothreitol (DTT) or glutathione the inhibition of enolase by either acrylamide or 2,5-hexanedione was potentiated. Activity of enolase inhibited by both acrylamide and DTT could not be restored to pre-inhibition rates following dialysis indicating that an irreversible interaction between acrylamide and enolase had taken place. The results suggest that neurotoxic compounds which produce distal axonopathies have a common pattern of attack on glycolytic enzymes and that interruption of glycolysis is the underlying biochemical basis for both the physiological and morphological damage caused by these compounds.
在大鼠脑中研究了神经毒性化合物丙烯酰胺和2,5 -己二酮对几种糖酵解酶的体外作用，这些酶包括烯醇化酶、磷酸果糖激酶（PFK）、甘油醛-3-磷酸脱氢酶（GAPDH）和乳酸脱氢酶（LDH）。观察到这些酶对神经毒素抑制作用的敏感性存在差异。对2,5 -己二酮敏感性增加的顺序为烯醇化酶--GAPDH--PFK，对丙烯酰胺的敏感性顺序为PFK--烯醇化酶--GAPDH。两种神经毒素均未抑制LDH。丙烯酰胺对烯醇化酶的抑制在双倒数图中呈现混合型模式。透析可使抑制作用完全逆转，表明其不涉及共价键形成。在二硫苏糖醇（DTT）或谷胱甘肽存在的情况下，丙烯酰胺或2,5 -己二酮对烯醇化酶的抑制作用增强。经丙烯酰胺和DTT抑制的烯醇化酶活性在透析后无法恢复到抑制前的水平，表明丙烯酰胺与烯醇化酶之间发生了不可逆相互作用。结果表明，产生远端轴突病的神经毒性化合物对糖酵解酶具有共同的攻击模式，糖酵解的中断是这些化合物所导致的生理和形态损伤的潜在生化基础。
