光辐射疗法中使用的卟啉与亚铁螯合酶的差异相互作用。
Differential interaction of porphyrins used in photoradiation therapy with ferrochelatase.
作者信息
Dailey H A, Smith A
出版信息
Biochem J. 1984 Oct 15;223(2):441-5. doi: 10.1042/bj2230441.
The mechanism of porphyrin accumulation by tumours is not yet established. If metabolism aids porphyrin elimination, tumours, unlike normal tissues, may not metabolize porphyrins used clinically, such as proto-, haemato-, OO'-diacetyl-haemato- and monohydroxyethyl-monovinyl-deutero-porphyrin. Proto-, haemato- and monohydroxyethyl-monovinyl-deutero-porphyrin are substrates for the mitochondrial enzyme ferrochelatase (EC 4.99.1.1), which can form haem analogues from exogenous porphyrins. The Km values for proto-, haemato- and monohydroxyethyl-monovinyl-deutero-porphyrin are 11, 22 and 23 microM respectively. However, OO'-diacetyl-haematoporphyrin is an effective competitive inhibitor with Ki of 11 microM. Hepatic ferrochelatase specific activity is 5.9 and 5.5 nmol of haem/h per mg of protein respectively in normal Buffalo rat and in those bearing the extrahepatic Morris 7288C hepatoma, and is only 0.13 nmol/h per mg in the hepatomas. Therefore low ferrochelatase activity in cancerous cells may provide one means whereby some porphyrins accumulate in tumours, and the ability of certain porphyrins to act as ferrochelatase inhibitors may provide another.
肿瘤积累卟啉的机制尚未明确。如果新陈代谢有助于卟啉的消除，那么与正常组织不同，肿瘤可能无法代谢临床上使用的卟啉，如原卟啉、血卟啉、OO'-二乙酰血卟啉和单羟乙基单乙烯基-氘代卟啉。原卟啉、血卟啉和单羟乙基单乙烯基-氘代卟啉是线粒体酶铁螯合酶（EC 4.99.1.1）的底物，该酶可从外源性卟啉形成血红素类似物。原卟啉、血卟啉和单羟乙基单乙烯基-氘代卟啉的Km值分别为11、22和23微摩尔。然而，OO'-二乙酰血卟啉是一种有效的竞争性抑制剂，Ki为11微摩尔。正常布法罗大鼠和患有肝外莫里斯7288C肝癌的大鼠肝脏中铁螯合酶的比活性分别为每毫克蛋白质5.9和5.5纳摩尔血红素/小时，而在肝癌中仅为每毫克0.13纳摩尔/小时。因此，癌细胞中铁螯合酶活性低可能是某些卟啉在肿瘤中积累的一种方式，而某些卟啉作为铁螯合酶抑制剂的能力可能是另一种方式。
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