{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:57:52Z","timestamp":1761217072546,"version":"3.37.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":10166,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1987,11]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Rats fed chow containing finely divided elemental iron (from carbonyl-iron) develop hepatic iron overload resembling human hereditary hemochromatosis in that deposition of iron is primarily in periportal hepatocytes and with hepatic iron concentrations sufficiently high to be associated in the human disease with hepatic fibrosis or cirrhosis. In recent studies using this model, we reported changes in hepatic hemoproteins and heme oxygenase, the rate-controlling enzyme of heme breakdown. We now report effects of iron-loading on three enzymes of heme synthesis: 5-aminolevulinate synthase; the first and rate-controlling enzyme of the pathway, 5-aminolevulinate dehydrase (or porphobilinogen synthase), and uroporphyrinogen decarboxylase, the activity of which is decreased in porphyria cutanea tarda, a liver disease in which iron is known to play an important but still poorly understood role. Of the three enzymes, only activity of the dehydrase was altered by iron-loading: it was decreased significantly as early as 1 week after starting iron feeding, and with marked iron overload was 30 to 32% of control values. The degree of decrease was inversely related (r = \u22120.77 to \u22120.88) to the degree of iron overload and was partially reversed within 1 to 3 days when feeding of the iron-supplemented diet was stopped. The decrease in dehydrase activity was not attributable to lack of reduced glutathione or other disulfide-reducing agents or to zinc deficiency; nor was evidence found for inhibition by iron compounds or other possible inhibitors present in iron-loaded livers. Immunochemical studies showed that the amount of 5-aminolevulinate dehydrase protein decreased in parallel to its decrease in activity, suggesting that iron-loading produced a reversible imbalance between the rate of synthesis and breakdown of the enzyme.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840070605","type":"journal-article","created":{"date-parts":[[2007,3,3]],"date-time":"2007-03-03T21:13:23Z","timestamp":1172956403000},"page":"1195-1203","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":27,"title":["Hepatic heme synthesis in a new model of experimental hemochromatosis: Studies in rats fed finely divided elemental iron"],"prefix":"10.1097","volume":"7","author":[{"given":"Herbert L.","family":"Bonkovsky","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John F.","family":"Healey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth","family":"Lincoln","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce R.","family":"Bacon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David F.","family":"Bishop","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George H.","family":"Elder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840070605-BIB1","first-page":"21","volume":"103","author":"Bonkovsky","year":"1979","journal-title":"Arch Pathol Lab Med"},{"key":"10.1002\/hep.1840070605-BIB2","first-page":"13","volume":"52","author":"Bonkovsky","year":"1979","journal-title":"Yale J Biol Med"},{"key":"10.1002\/hep.1840070605-BIB3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1042\/bj1960057","volume":"196","author":"Bonkovsky","year":"1981","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840070605-BIB4","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1172\/JCI110866","volume":"71","author":"Bonkovsky","year":"1983","journal-title":"J Clin Invest"},{"key":"10.1002\/hep.1840070605-BIB5","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0014-5793(73)80545-9","volume":"29","author":"DeMatteis","year":"1973","journal-title":"FEBS Lett"},{"key":"10.1002\/hep.1840070605-BIB6","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1042\/bj1800257","volume":"180","author":"Ibrahim","year":"1979","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840070605-BIB7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1042\/bj2000035","volume":"200","author":"Ibrahim","year":"1981","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840070605-BIB8","first-page":"351","volume-title":"Hepatology: a textbook of liver disease","author":"Bonkovsky","year":"1982","unstructured":"Porphyrin and heme metabolism and the porphyrias. 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