Samet M K, Rutledge C O
Biochem Pharmacol. 1984 Nov 15;33(22):3547-51. doi: 10.1016/0006-2952(84)90135-7.
A change in the fluidity of biological membranes can be produced by methylation reactions which sequentially transfer methyl groups from phosphatidylethanolamine to phosphatidylcholine. Since the physical properties of membranes may affect the function of membrane-localized transport proteins, the accumulation of norepinephrine (NE) by rat cortical synaptosomes was examined in the presence of S-adenosylhomocysteine (AdoHcy) which inhibits the methylation of phospholipids. A concentration-related decrease in the uptake of [3H]NE was produced by AdoHcy with coincident decreases in the S-adenosylmethionine (AdoMet)-dependent transmethylation of phospholipids in neuronal membranes. A kinetic analysis for the effects of AdoHcy on the neuronal uptake of NE revealed a significant decrease in both the apparent Km and Vmax. Treatment of synaptosomes with adenosine, L-homocysteine thiolactone (HTL), and erythro-9(2-hydroxy-3-nonyl)adenine (EHNA) which leads to the synthesis of intracellular AdoHcy resulted in a decrease in the Vmax with no significant change in the Km. Adenosine or EHNA alone had no effect on NE uptake, but HTL alone significantly inhibited NE uptake. The data suggest that the processes of enzymatic methylation of membrane phospholipids and the transport of norepinephrine may be associated within neuronal membranes. Inhibiting phospholipid methylation reactions can reduce the efficiency of neurotransmitter removal and perhaps indirectly alter synaptic function.
甲基化反应可导致生物膜流动性的改变，该反应能将甲基基团依次从磷脂酰乙醇胺转移至磷脂酰胆碱。由于膜的物理性质可能会影响膜定位转运蛋白的功能，因此在存在抑制磷脂甲基化的S-腺苷同型半胱氨酸（AdoHcy）的情况下，检测了大鼠皮质突触体对去甲肾上腺素（NE）的摄取。AdoHcy导致[3H]NE摄取呈浓度依赖性降低，同时神经元膜中依赖S-腺苷甲硫氨酸（AdoMet）的磷脂转甲基作用也降低。对AdoHcy对神经元摄取NE的影响进行动力学分析发现，表观Km和Vmax均显著降低。用腺苷、L-同型半胱氨酸硫内酯（HTL）和赤藓红-9（2-羟基-3-壬基）腺嘌呤（EHNA）处理突触体，这些物质会导致细胞内AdoHcy的合成，结果导致Vmax降低，而Km无显著变化。单独使用腺苷或EHNA对NE摄取无影响，但单独使用HTL可显著抑制NE摄取。数据表明，膜磷脂的酶促甲基化过程与去甲肾上腺素的转运过程可能在神经元膜内存在关联。抑制磷脂甲基化反应可降低神经递质清除效率，可能间接改变突触功能。
