Guo R, Lim C K, De Matteis F
MRC Toxicology Unit, University of Leicester, UK.
Biomed Chromatogr. 1996 Sep-Oct;10(5):213-20. doi: 10.1002/(SICI)1099-0801(199609)10:5<213::AID-BMC592>3.0.CO;2-D.
In previous work certain hydroxylated and peroxylated derivatives of uroporphyrin (URO) have been isolated from the urine of patients suffering from porphyria. We have now investigated the mechanism of production of these oxygenated derivatives of URO, using both enzymic and chemical model systems and also the effect of exposure to light during reoxidation of uroporphyrinogen (URO'gen). When URO'gen was incubated with haemolysates, peaks with the same retention times as peroxyacetic acid URO, meso-hydroxy URO and beta-hydroxypropionic acid URO were all detected. The first of these was formed in sufficient amounts to allow its characterization by mass spectrometry. Under these conditions, peroxyacetic acid derivatives of heptacarboxylate and pentacarboxylate porphyrins could also be produced from the corresponding porphyrinogens, but no peroxylated product could be obtained from coproporphyrinogen (COPRO'gen, where no acetic acid side chains are present) or from the fully oxidized URO. Similar results were obtained on re-oxidation of URO'gen in the xanthine oxidase-xanthine system and in the presence of hydrogen peroxide/Fe-EDTA (ethylenediamine-tetraacetic acid) and here again no peroxylated product could be detected from either COPRO'gen or URO. Finally, formation of peroxyacetic acid URO could be demonstrated during photo-oxidation of URO'gen and this was followed by light-induced loss of both URO and its peroxylated derivative. It is concluded that the oxygenated derivatives arise from the action of reactive oxygen species on the porphyrinogens (rather than the porphyrins), with one of the acetic acid side chain serving as the preferential (or exclusive target) for peroxylation.
在之前的研究工作中，已从患有卟啉症患者的尿液中分离出尿卟啉（URO）的某些羟基化和过氧化衍生物。我们现在利用酶促和化学模型系统研究了这些URO氧化衍生物的产生机制，以及在尿卟啉原（URO'gen）再氧化过程中光照的影响。当URO'gen与溶血产物一起孵育时，检测到了与过氧乙酸URO、中羟基URO和β - 羟基丙酸URO保留时间相同的峰。其中第一种形成的量足以通过质谱对其进行表征。在这些条件下，七羧酸盐和五羧酸盐卟啉的过氧乙酸衍生物也可由相应的卟啉原产生，但从粪卟啉原（COPRO'gen，不存在乙酸侧链）或完全氧化的URO中无法获得过氧化产物。在黄嘌呤氧化酶 - 黄嘌呤系统以及存在过氧化氢/铁 - 乙二胺四乙酸（Fe - EDTA）的情况下对URO'gen进行再氧化时也得到了类似结果，并且在此同样从COPRO'gen或URO中检测不到过氧化产物。最后，在URO'gen的光氧化过程中可证明过氧乙酸URO的形成，随后URO及其过氧化衍生物在光照下均会损失。得出的结论是，氧化衍生物源于活性氧对卟啉原（而非卟啉）的作用，其中一个乙酸侧链作为过氧化的优先（或唯一）靶点。
