Distribution of metalloporphyrin inhibitors of heme oxygenase among serum transport proteins.
Porphyrins are transported in the serum bound to proteins and lipoproteins; the particular component(s) to which a porphyrin is bound influences its distribution in the body. In these experiments, the fractions of serum to which several metalloporphyrin inhibitors of the microsomal enzyme heme oxygenase bind were determined. Sn-mesoporphyrin and Sn-protoporphyin were associated almost entirely with serum albumin and Sn-diiododeuteroporphyrin almost completely with the lipoprotein fraction; Zn-mesoporphyrin was associated with all fractions. Serum transport proteins may be targets of photosensitization by photoactive metalloporphyrins. A decrease in the binding constant of bilirubin to Sn-mesoporphyrin-mediated photosensitized human serum albumin (HSA) was observed following illumination at 50 W/m2 in the spectral range of 520-700 nm; there were 2.0 +/- 0.2 bilirubins bound per HSA for samples illuminated < 120 min; following 180 min illumination, the stoichiometry decreased to 1.5 +/- 0.1 bilirubin per HSA. In a similar experiment with Zn-mesoporphyrin, the porphyrin was fully photooxidized to a nonphotoactive and noninhibiting product after 1 min illumination. The light reaching a porphyrin through human skin would be considerably less than that utilized under these in vitro conditions, and such effects on serum proteins, if demonstrable at all in vivo, would be expected to be far less pronounced than those measured here.
Rockefeller University Hospital, New York, NY 10021.
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Greenbaum
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Kappas
D001663:Bilirubin / Q000378:metabolism*; D001667:Binding, Competitive; D002104:Cadmium / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood*; D003905:Deuteroporphyrins / Q000097:blood; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006801:Humans; D008652:Mesoporphyrins / Q000378:metabolism / Q000494:pharmacology; D008665:Metalloporphyrins / Q000097:blood / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology; D012709:Serum Albumin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D014001:Tin / Q000378:metabolism; D014018:Tissue Distribution; D015032:Zinc / Q000378:metabolism
D002352:Carrier Proteins; D003905:Deuteroporphyrins; D008652:Mesoporphyrins; D008665:Metalloporphyrins; D012709:Serum Albumin; D002104:Cadmium; C031468:mesoporphyrin IX; D014001:Tin; D006419:Heme Oxygenase (Decyclizing); D015032:Zinc; D001663:Bilirubin