2-氨基己二酸是衰老人体皮肤中蛋白质羰基氧化的标志物：糖尿病、肾衰竭和败血症的影响。
2-aminoadipic acid is a marker of protein carbonyl oxidation in the aging human skin: effects of diabetes, renal failure and sepsis.
作者信息
Sell David R, Strauch Christopher M, Shen Wei, Monnier Vincent M
机构信息
Department of Pathology, Case Western Reserve University, Wolstein Research Building, 2103 Cornell Road, Cleveland, OH 44106, USA.
出版信息
Biochem J. 2007 Jun 1;404(2):269-77. doi: 10.1042/BJ20061645.
We hypothesized that the epsilon-amino group of lysine residues in longlived proteins oxidatively deaminates with age forming the carbonyl compound, allysine (alpha-aminoadipic acid-delta-semialdehyde), which can further oxidize into 2-aminoadipic acid. In the present study, we measured both products in insoluble human skin collagen from n=117 individuals of age range 10-90 years, of which n=61 and n=56 were non-diabetic and diabetic respectively, and a total of n=61 individuals had either acute or chronic renal failure. Allysine was reduced by borohydride into 6-hydroxynorleucine and both products were measured in acid hydrolysates by selective ion monitoring gas chromatography (GC)-MS. The results showed that 2-aminoadipic acid (P<0.0001), but not 6-hydroxynorleucine (P=0.14), significantly increased with age reaching levels of 1 and 0.3 mmol/mol lysine at late age respectively. Diabetes in the absence of renal failure significantly (P<0.0001) increased 2-aminoadipic acid up to <3 mmol/mol, but not 6-hydroxynorleucine (levels<0.4 mmol/mol, P=0.18). Renal failure even in the absence of diabetes markedly increased levels reaching up to <0.5 and 8 mmol/mol for 6-hydroxynorleucine and 2-aminoadipic acid respectively. Septicaemia significantly (P<0.0001) elevated 2-aminoadipic acid in non-diabetic, but not diabetic individuals, and mildly correlated with other glycoxidation markers, carboxymethyl-lysine and the methylglyoxal-derived products, carboxyethyl-lysine, argpyrimidine and MODIC (methylglyoxal-derived imidazolium cross-link). These results provide support for the presence of metal-catalysed oxidation (the Suyama pathway) in diabetes and the possible activation of myeloperoxidase during sepsis. We conclude that 2-aminoadipic acid is a more reliable marker for protein oxidation than its precursor, allysine. Its mechanism of formation in each of these conditions needs to be elucidated.
我们推测，长寿蛋白中赖氨酸残基的ε-氨基会随着年龄增长发生氧化脱氨反应，形成羰基化合物烯赖氨酸（α-氨基己二酸-δ-半醛），后者可进一步氧化为2-氨基己二酸。在本研究中，我们检测了年龄在10至90岁之间的117名个体的不溶性人皮肤胶原蛋白中的这两种产物，其中61名非糖尿病患者，56名糖尿病患者，共有61名个体患有急性或慢性肾衰竭。烯赖氨酸经硼氢化物还原为6-羟基正亮氨酸，两种产物在酸性水解产物中通过选择性离子监测气相色谱（GC）-质谱法进行检测。结果显示，2-氨基己二酸（P<0.0001）而非6-羟基正亮氨酸（P=0.14）随年龄显著增加，在老年时分别达到1和0.3 mmol/mol赖氨酸的水平。无肾衰竭的糖尿病患者2-氨基己二酸显著增加（P<0.0001），最高可达<3 mmol/mol，但6-羟基正亮氨酸未增加（水平<0.4 mmol/mol，P=0.18）。即使无糖尿病，肾衰竭也会显著提高水平，6-羟基正亮氨酸和2-氨基己二酸分别高达<0.5和8 mmol/mol。败血症在非糖尿病个体中显著（P<0.0001）升高2-氨基己二酸，但在糖尿病个体中未升高，且与其他糖氧化标记物、羧甲基赖氨酸以及甲基乙二醛衍生产物羧乙基赖氨酸、精脒嘧啶和MODIC（甲基乙二醛衍生的咪唑交联物）轻度相关。这些结果为糖尿病中金属催化氧化（Suyama途径）的存在以及败血症期间髓过氧化物酶可能的激活提供了支持。我们得出结论，2-氨基己二酸比其前体烯赖氨酸是更可靠的蛋白质氧化标记物。需要阐明在每种这些情况下其形成机制。
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