Properties of human kidney heme oxygenase: inhibition by synthetic heme analogues and metalloporphyrins.
Heme oxygenase activities in human kidney microsomes were found to be from 0.238 to 0.620 nmol of bilirubin/mg/hr (mean 0.375, SD 0.134), which represent approximately 30% of activities determined for human adult liver. There was interindividual variation in heme oxygenase activity of a 2-5-fold difference. Rabbits were immunized with purified human liver heme oxygenase and the resulting antibody preparation was used to examine the species specificity of the enzyme. Microsomal protein with a molecular weight of 32,000 from human kidney was identified on Western blots by its reaction with the anti-heme oxygenase liver antibody similar to the purified enzyme protein. Thus, a homology exists between human hepatic and kidney heme oxygenase. The enzyme activity was sensitive to inhibition by metalloporphyrins, such as tin-protoporphyrin IX and, to a lesser degree, by zinc and cobalt protoporphyrin IX. In a study of different synthetic heme analogues for in vitro inhibition of heme oxygenase, we found that replacement of iron by zinc in deuteroporphyrin IX 2,4 bis glycol dramatically potentiated the inhibition of heme oxygenase activity. This finding demonstrated that zinc deuteroporphyrin IX 2,4 bis glycol is a most potent inhibitor of heme oxygenase activity.
Martasek
P
P
Department of Medicine, New York Medical College, Valhalla 10595.
Solangi
K
K
Goodman
A I
AI
Levere
R D
RD
Chernick
R J
RJ
Abraham
N G
NG
D015153:Blotting, Western; D006418:Heme / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D008665:Metalloporphyrins / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D008665:Metalloporphyrins; D006418:Heme; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing)