BACKGROUND & AIMS:
:Alcoholism plays a major role in the insufficient utilization or deficiency of the vitamin B-complex molecules, and the pathologies resulting therefrom. Thiamine, pyridoxamine, and folic acid, each contain primary amine functional groups, whereas nicotinamide and vitamin B12 contain amide groups, each of which are potential reactants with acetaldehyde (AcH), the primary intermediate in the metabolism of ethanol. In this current study, it is reported that prothrombin time (PT), which is prolonged in a fraction of the alcoholic population, can be modified (in the laboratory) when several B-complex vitamins and AcH are added successively to human plasma or are premixed prior to the addition to plasma. Particularly, thiamine, pyridoxamine, and folic acid, at 0.01 mol/l, when added successively with 44.7 mmol/l AcH to plasma, or when premixed prior to addition to plasma, produced a marked reduction in the anticoagulant effect of AcH. Nicotinamide had no effect on PT nor did mixtures with AcH effect PT. However, NAD, which contains a primary amine in its AMP moiety, reacted with AcH, lowering the latter's anticoagulant activity upon addition to plasma. Vitamin B12 did not affect PT. Interestingly, successive mixtures of vitamin B12 and AcH to plasma resulted in a small but statistically significant increase (P≤0.05) in the anticoagulant effect of AcH, whereas premixtures had no statistically significant effect (P>0.05). The decrease in anticoagulant activity of AcH in the presence of B-complex vitamins and NAD suggests that the primary amines in these molecules may form Schiff bases with AcH, thereby lowering both the free AcH concentration as well as the ability of the free vitamins/coenzymes to partake in essential physiological reactions.
背景与目标:
: 酒精中毒在维生素b复合物分子的利用不足或缺乏以及由此引起的病理中起主要作用。硫胺素,吡哆胺和叶酸各自包含伯胺官能团,而烟酰胺和维生素B12包含酰胺基团,它们各自是乙醛 (AcH) 的潜在反应物,乙醛是乙醇代谢的主要中间体。在这项当前的研究中,据报道,当将几种B复合维生素和AcH相继添加到人血浆中或在添加到血浆之前进行预混时,可以 (在实验室中) 改变凝血酶原时间 (PT),该时间在酒精人群的一小部分中延长。特别地,当0.01 mol/l的硫胺素、吡哆胺和叶酸与44.7 mmol/l的AcH连续添加到血浆中时,或者当在添加到血浆之前预混合时,AcH的抗凝血作用显著降低。烟酰胺对PT没有影响,与AcH效应PT的混合物也没有影响。然而,在其AMP部分中包含伯胺的NAD与AcH反应,在添加到血浆中后降低了AcH的抗凝血活性。维生素B12不影响PT。有趣的是,维生素B12和AcH与血浆的连续混合物导致AcH的抗凝作用小幅但统计学上显著的增加 (P ≤ 0.05),而预混物没有统计学上显著的影响 (P>0.05)。在存在B复合维生素和NAD的情况下,AcH的抗凝血活性降低表明这些分子中的伯胺可能与AcH形成席夫碱,从而降低了游离AcH的浓度以及游离维生素的能力/辅酶参与基本的生理反应。