Control of heme oxygenase and plasma levels of bilirubin by a synthetic heme analogue, tin-protoporphyrin.
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)
D000328:Adult; D000818:Animals; D001663:Bilirubin / Q000097:blood*; D006419:Heme Oxygenase (Decyclizing) / Q000097:blood*; D006801:Humans; D007565:Jaundice / Q000188:drug therapy; D008665:Metalloporphyrins; D008670:Metals / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000097:blood*; D009942:Organometallic Compounds / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats
D008665:Metalloporphyrins; D008670:Metals; D009942:Organometallic Compounds; D011166:Porphyrins; D011524:Protoporphyrins; C032628:tin protoporphyrin IX; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing); D001663:Bilirubin