Stadtman E R
Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Annu Rev Biochem. 1993;62:797-821. doi: 10.1146/annurev.bi.62.070193.004053.
Basic mechanisms that underlie the oxygen free radical-promoted oxidation of free amino acids and amino acid residues of proteins are derived from radiolysis studies. Results of these studies indicate that the most common pathway for the oxidation of simple aliphatic amino acids involves the hydroxyl radical-mediated abstraction of a hydrogen atom to form a carbon-centered radical at the alpha-position of the amino acid or amino acid residue in the polypeptide chain. Addition of O2 to the carbon-centered radicals leads to formation of peroxy radical derivatives, which upon decomposition lead to production of NH3 and alpha-ketoacids, or to production of NH3, CO2, and aldehydes or carboxylic acids containing one less carbon atom. As the number of carbon atoms in the amino acid is increased, hydrogen abstraction at other positions in the carbon chain becomes more important and leads either to the formation of hydroxy derivatives, or to amino acid cross-linked products as a consequence of carbon-centered radical recombination processes. alpha-Hydrogen abstraction plays a minor role in the oxidation of aromatic amino acids by radiolysis. Instead, the aromatic ring is the primary site of attack leading to hydroxy derivatives, to ring scission, and in the case of tyrosine to the formation of Tyr-Tyr cross-linked dimers. The basic pattern for the oxidation of amino acids by metal ion-catalyzed reactions (Fenton chemistry) is similar to the alpha-hydrogen abstraction pathway. But unlike the case of oxidation by radiolysis, this Fenton pathway is the major mechanism for the oxidation of all aliphatic amino acids, regardless of chain length, as well as for the oxidation of aromatic amino acids. Curiously, the Fe(III)-catalyzed oxidation of free amino acids is almost completely dependent upon the presence of bicarbonate ion, and is greatly stimulated by iron chelators at chelator/Fe(III) ratios less than 1.0, and is inhibited at chelator/Fe(III) ratios greater than 1.0. It is deduced that the most active catalytic complex is composed of two equivalents of HCO3-, an amino acid, and at least one equivalent of iron; however, two forms of iron, an iron-chelate and another form, must somehow be involved. In contrast to the situation with radiolysis, the aromatic rings of aromatic amino acids are only minor targets for metal-catalyzed reactions. All amino acid residues in proteins are subject to attack by hydroxyl radicals generated by ionizing radiation; however, the aromatic amino acids and sulfur-containing amino acids are most sensitive to oxidation.(ABSTRACT TRUNCATED AT 400 WORDS)
自由基促进的游离氨基酸和蛋白质氨基酸残基氧化的基本机制源自辐射分解研究。这些研究结果表明，简单脂肪族氨基酸氧化的最常见途径涉及羟基自由基介导的氢原子提取，在氨基酸或多肽链中氨基酸残基的α位形成以碳为中心的自由基。向以碳为中心的自由基中添加O2会导致过氧自由基衍生物的形成，这些衍生物分解后会产生NH3和α-酮酸，或者产生NH3、CO2以及含碳原子数少一个的醛或羧酸。随着氨基酸中碳原子数的增加，碳链中其他位置的氢提取变得更加重要，并导致羟基衍生物的形成，或者由于以碳为中心的自由基重组过程而形成氨基酸交联产物。α-氢提取在辐射分解对芳香族氨基酸的氧化中起次要作用。相反，芳香环是主要的攻击位点，会导致羟基衍生物的形成、环断裂，对于酪氨酸而言，还会形成Tyr-Tyr交联二聚体。金属离子催化反应（芬顿化学）中氨基酸氧化的基本模式与α-氢提取途径相似。但与辐射分解氧化的情况不同，这种芬顿途径是所有脂肪族氨基酸（无论链长如何）以及芳香族氨基酸氧化的主要机制。奇怪的是，Fe(III)催化的游离氨基酸氧化几乎完全依赖于碳酸氢根离子的存在，并且在螯合剂/Fe(III)比率小于1.0时受到铁螯合剂的极大刺激，而在螯合剂/Fe(III)比率大于1.0时受到抑制。据推断，最活跃的催化复合物由两当量的HCO3-、一个氨基酸和至少一当量的铁组成；然而，两种形式的铁，一种铁螯合物和另一种形式，必须以某种方式参与其中。与辐射分解的情况相反，芳香族氨基酸的芳香环只是金属催化反应的次要靶点。蛋白质中的所有氨基酸残基都容易受到电离辐射产生的羟基自由基的攻击；然而，芳香族氨基酸和含硫氨基酸对氧化最敏感。（摘要截于400字）
