Kappas A, Drummond G S, Simionatto C S, Anderson K E
Hepatology. 1984 Mar-Apr;4(2):336-41. doi: 10.1002/hep.1840040227.
The catalytic site of heme oxygenase recognizes metalloporphyrins with central metal atoms other than iron; it favors some of these metalloporphyrins over heme as a potential substrate sometimes by a large factor, permitting the synthetic heme analogue to serve as a potent competitive inhibitor of the heme oxygenase reaction. Since these synthetic metalloporphyrins do not bind molecular oxygen, they are not metabolically degraded by ring rupture and do not add to the body pool of bile pigment. One possible consequence of this competitive inhibition of heme degradation is suppression of bile pigment formation to such a degree that excessive plasma levels of bilirubin may be diminished. That the latter phenomenon occurs was shown for the first time by our study in 1981 (6), and by subsequent investigations in rats, mice, monkeys and man. The compound does not appear to affect the metabolic disposition of preformed bilirubin but inhibits biliary bilirubin excretion derived from the metabolism of endogenous or exogenous heme. Whether some of the effect of Sn-protoporphyrin on naturally occurring or experimentally induced jaundice in animals reflects diversion of heme to nonheme oxygenase-dependent pathways of heme metabolism or whether a pathway which is normally latent becomes activated concurrent with heme oxygenase inhibition is not known. Sn-protoporphyrin is remarkably innocuous in the newborn rat and may prove so in man.(ABSTRACT TRUNCATED AT 250 WORDS)
血红素加氧酶的催化位点能够识别中心金属原子不是铁的金属卟啉；它有时会将其中一些金属卟啉作为潜在底物优先于血红素，且优势明显，使得合成血红素类似物能够作为血红素加氧酶反应的强效竞争性抑制剂。由于这些合成金属卟啉不结合分子氧，它们不会通过环断裂进行代谢降解，也不会增加体内胆汁色素池。这种对血红素降解的竞争性抑制的一个可能后果是胆汁色素形成受到抑制，以至于过高的血浆胆红素水平可能会降低。1981年我们的研究首次证明了后一种现象的发生(6)，随后在大鼠、小鼠、猴子和人类身上也有相关研究。该化合物似乎不会影响预先形成的胆红素的代谢处置，但会抑制内源性或外源性血红素代谢产生的胆汁胆红素排泄。锡原卟啉对动物自然发生或实验诱导的黄疸的某些作用，是反映血红素转向非血红素加氧酶依赖性血红素代谢途径，还是反映一条通常潜伏的途径在血红素加氧酶抑制的同时被激活，目前尚不清楚。锡原卟啉在新生大鼠中非常无害，在人类中可能也是如此。（摘要截短至250字）
