Postulated deficiency of hepatic heme and repair by hematin infusions in the "inducible" hepatic porphyrias.
There is compelling, indirect evidence of hepatic heme deficiency due primarily to the respective genetic errors of the three inducible hepatic porphyrias, acute intermittent porphyria, porphyria variegata, and hereditary coproporphyria. The induction is enhanced by exogenous inducers such as barbiturate, estrogens and other "porphyrogenic" chemicals and factors, including glucose deprivation. The newer knowledge of the induction of delta-aminolevulinic acid synthetase [delta-aminolevulinate synthase; succinyl--CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37] in relation to inadequate heme, and repression by heme, stimulated early trials of hematin infusions to overcome the acute relapse in the foregoing inducible porphyrias. Recently this experience has been considerably expanded, 143 infusions of hematin having been given in 22 cases. Studies of the effect on the serum concentrations of delta-aminolevulinic acid and porphobilinogen have shown a highly significant decline, often to 0, especially of delta-aminolevulinic acid. A distinct relationship to the clinical severity of the attack has been evident in the frequency and magnitude of decline of serum delta-aminolevulinic acid and porphobilinogen. This was regularly associated with objective clinical improvement.
D000624:5-Aminolevulinate Synthetase / Q000097:blood; D000328:Adult; D005260:Female; D006418:Heme / Q000031:analogs & derivatives* / Q000172:deficiency*; D006427:Hemin / Q000627:therapeutic use*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D011162:Porphobilinogen / Q000097:blood; D011164:Porphyrias / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism
D006418:Heme; D006427:Hemin; D011162:Porphobilinogen; D000624:5-Aminolevulinate Synthetase
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