title: Postulated deficiency of hepatic heme and repair by hematin infusions in the "inducible" hepatic porphyrias.
abstract: 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.
mesh_terms: 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
chemical_list: D006418:Heme; D006427:Hemin; D011162:Porphobilinogen; D000624:5-Aminolevulinate Synthetase
references.citation: Proc Natl Acad Sci U S A. 1965 Apr;53:841-7
references.pmid: 14329695
references.citation: J Psychosom Res. 1962 Jan-Mar;6:1-24
references.pmid: 13859189
references.citation: JAMA. 1964 Nov 9;190:501-4
references.pmid: 14198005
references.citation: Metabolism. 1964 May;13:396-406
references.pmid: 14169218
references.citation: J Biol Chem. 1963 Feb;238:821-7
references.pmid: 13949831
references.citation: Lancet. 1976 Dec 4;2(7997):1217-9
references.pmid: 63041
references.citation: Proc Natl Acad Sci U S A. 1971 Nov;68(11):2725-9
references.pmid: 5288250
references.citation: Arch Intern Med. 1966 Sep;118(3):229-40
references.pmid: 5947302
references.citation: Enzyme. 1973;16(1):354-66
references.pmid: 4791054
references.citation: Ann Intern Med. 1973 Jul;79(1):80-3
references.pmid: 4721179
references.citation: J Biol Chem. 1975 Jun 10;250(11):4171-7
references.pmid: 1126948
references.citation: N Engl J Med. 1975 Sep 18;293(12):605-7
references.pmid: 1152896
references.citation: Proc Natl Acad Sci U S A. 1974 Feb;71(2):278-82
references.pmid: 4521800
references.citation: Clin Chem. 1974 Nov;20(11):1438-40
references.pmid: 4425514
references.citation: JAMA. 1976 Feb 2;235(5):520-2
references.pmid: 946099
references.citation: Ann Intern Med. 1975 Jul;83(1):20-30
references.pmid: 1147435
references.citation: Proc Natl Acad Sci U S A. 1970 Nov;67(3):1315-20
references.pmid: 5274461
references.citation: J Lab Clin Med. 1971 Nov;78(5):683-95
references.pmid: 5128821
references.citation: N Engl J Med. 1970 Oct 29;283(18):954-8
references.pmid: 5470255
references.citation: Trans Assoc Am Physicians. 1969;82:363-71
references.pmid: 5375159
references.citation: Biochem Biophys Res Commun. 1966 Sep 8;24(5):675-83
references.pmid: 5970500
references.citation: J Biol Chem. 1966 Mar 25;241(6):1359-75
references.pmid: 5935350