Studies on the inhibitory effect of vitamin E against secondary reaction of lipid peroxidation

不饱和脂肪在过氧化过程中的氧化裂解会产生细胞毒性和遗传毒性的α，β-不饱和醛，如4-羟基-2-壬烯醛(HNE)和4-氧-2-壬烯醛(ONE)。我们研究了维生素E与HNE或HNE的反应活性，以阐明维生素E在α，β-不饱和醛解毒中的作用。维生素E中活性最强的Α-生育酚(α-TH)不与这些醛反应，而Y-和δ-TH在酸性条件下能与一种或两种HNE反应。其中一种是已知的第二类脂质过氧化产物中反应性最强的醛。因此，我们研究了Y-TH与1，4-丙酮的反应产物。在盐酸存在下，Y-TH与Y-TH反应37℃时，用反相高效液相色谱法检测到产物峰1-3。分离得到化合物1-3，其结构经核磁共振确证。化合物1被确定为5-(1-(呋喃-2-基)戊基)-y-生育酚，是y-TH与1的加成产物。化合物2也是Y-TH与1的加成产物，其中Y-TH的C-5位和6-羟基与1的C-5和C-4位结合。化合物3是γ-TH与两个1分子的加成产物，其中化合物2中一个残基的C-1位置与另一个分子的C-5位置结合。S-TH还可以与一种化合物反应生成一些加成产物，但其结构尚不清楚。结果表明，Y-TH和8-TH是植物种子中维生素E的主要存在形式，是植物种子中维生素E的主要存在形式。因此，γ-TH可以捕获膜上可溶的α，β-不饱和醛，在它们破坏重要的生物分子之前形成以非活性碳为中心的加合物。

Oxidative cleavage of unsaturated lipids during peroxidation gives rise to cytotoxic and genotoxic a,β-unsaturated aldehydes, such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE). We have studied the reactivity of vitamin E with HNE or ONE to clarify the role of vitamin E on the detoxification of α,β-unsaturated aldehydes. Α-Tocopherol (α-TH), the most active vitamin E, did not react with these aldehydes, whereas y- and δ- THs could react with ONE or HNE under the acidic conditions. ONE is known to be the most reactive aldehyde among the secondary of lipid peroxidation products. Therefore, the reaction products of y-TH with ONE have been investigated. When y-TH was reacted with ONE at 37℃ in the presence of HC1, product peaks 1-3 were detected by reversed-phase HPLC. Compounds 1-3 were isolated and their structures were determined by NMR. Compound 1 was determined to be 5- (1- (furan-2-yl) pentyl) -y-tocopherol, the addition product of y-TH with ONE. Compound 2 was also the addition product of y-TH with ONE where the C-5 position and 6-hydroxyl group of y-TH were bound to the C-5 and C-4 positions of ONE. Compound 3 was the addition product of γ-TH with two ONE molecules where the C-1 position of ONE residue in compound 2 was bound to the C-5 position of another ONE molecule. S-TH could also react with ONE to form some addition products although their structures were still unknown. The results indicate that y- and 8-THs which possess nucleophilic character in the chroman ring can act as scavengers of lipophilic electrophiles such as ONE.y-TH is the major form of vitamin E in plant seeds and consequently in our diet. Thus, γ-TH may trap the membrane-soluble α,β-unsaturated aldehydes to form unreactive carbon-centered adducts before they can damage important biological molecules.