Studies on the efflux of metalloporphyrin from rat-liver mitochondria. Effect of albumin, globin, haemin and haemoglobin.
The mechanism by which metalloporphyrins escape from mitochondria has been studied in isolated rat-liver mitochondria using Co-deuteroporphyrin as the model compound. During the first 10--15 min of incubation the efflux is about 10% of the total amount of Co-deuteroporphyrin synthesized. The efflux then increases to a second steady-state leve of 25--35% after 30--45 min of incubation. The efflux is inversely correlated to the energy state of the mitochondria. Globin at concentrations less than 0.4 mumol/l enhances the efflux of Co-deuteroporphyrin, but has no effect on the degree of energy coupling or on the rate of Co-deuteroporphyrin synthesis. The effect of globin can be competitively inhibited by adding haemin. Haemin (0.5--1.0 mumol/l) when added to the medium in the absence of globin reduces the efflux of Co-deuteroporphyrin by 20--30%, but has no effect on the metal-chelatase activity. Neither albumin nor haemoglobin increases the efflux of Co-deuteroporphyrin from intact mitochondria. The results suggest that the efflux of metalloporphyrin is regulated in part by the energy state of the mitochondria and in part by the presence of metalloporphyrin-binding ligants and unattached haemin in the incubation medium.
D000818:Animals; D003905:Deuteroporphyrins / Q000378:metabolism*; D005914:Globins / Q000494:pharmacology*; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000494:pharmacology*; D006454:Hemoglobins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D011166:Porphyrins / Q000378:metabolism*; D051381:Rats; D012709:Serum Albumin / Q000494:pharmacology*
D003905:Deuteroporphyrins; D006454:Hemoglobins; D011166:Porphyrins; D012709:Serum Albumin; D006418:Heme; D006427:Hemin; D005914:Globins