Regulation of intestinal iron absorption and mucosal iron kinetics in hereditary hemochromatosis
- PMID: 2019794
Regulation of intestinal iron absorption and mucosal iron kinetics in hereditary hemochromatosis
Abstract
In hereditary hemochromatosis (HH), increased intestinal iron absorption leads to the development of iron overload. To examine the abnormal regulation of iron absorption in this disorder, we analyzed mucosal iron kinetics in six patients with HH and in five normal subjects by using a compartmental model of intestinal iron absorption and systemic ferrokinetics. Subjects were given simultaneous oral and intravenous tracer doses of iron 59-labeled citrate and iron 55-labeled transferrin, respectively. Plasma and whole-body radioactive iron levels were then monitored serially during the next 2 weeks, and mucosal iron transport rate constants were estimated by non-linear least-squares fit of the model to these data. Iron absorption was inversely related to serum ferritin concentration in both normal subjects and patients with HH but was higher in relation to serum ferritin level among the latter (p less than 0.0002). Analysis of mucosal iron kinetics demonstrated a similar inverse relationship between the rate constant for mucosal iron uptake and serum ferritin among all subjects combined, but the mean uptake rate constant in patients with HH did not differ from that of normal subjects (p = 0.71). The mean rate constant for incorporation of iron into the mucosal storage pool in patients with HH also was comparable to that of normal subjects (p = 0.94). In contrast, the rate constant for transfer of mucosal iron to the plasma was higher in patients with HH than in normal subjects for any given serum ferritin level (p less than 0.0001), and the transfer rate constant accounted for 87% of the variability in iron absorption among all subjects. We conclude that the increased iron absorption in HH is mediated primarily by an increase in the rate constant for transfer of mucosal iron to the plasma.
Similar articles
-
Iron absorption and hepatic iron uptake are increased in a transferrin receptor 2 (Y245X) mutant mouse model of hemochromatosis type 3.Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G323-8. doi: 10.1152/ajpgi.00278.2006. Epub 2006 Aug 24. Am J Physiol Gastrointest Liver Physiol. 2007. PMID: 16935854
-
In vitro studies of duodenal iron uptake in patients with primary and secondary iron storage disease.Q J Med. 1980;49(195):249-57. Q J Med. 1980. PMID: 7465761
-
Iron overload disorders: natural history, pathogenesis, diagnosis, and therapy.Crit Rev Clin Lab Sci. 1983;19(3):205-66. doi: 10.3109/10408368309165764. Crit Rev Clin Lab Sci. 1983. PMID: 6373141 Review.
-
Biochemistry of nonheme iron in man. II. Absorption of iron.Clin Physiol Biochem. 1989;7(2):53-69. Clin Physiol Biochem. 1989. PMID: 2667838 Review.
-
Duodenal ferritin content and structure: relationship with body iron stores in man.Arch Intern Med. 1978 Jul;138(7):1109-13. Arch Intern Med. 1978. PMID: 666470
Cited by
-
Iron Absorption: Molecular and Pathophysiological Aspects.Metabolites. 2024 Apr 17;14(4):228. doi: 10.3390/metabo14040228. Metabolites. 2024. PMID: 38668356 Free PMC article. Review.
-
Hemochromatosis: Ferroptosis, ROS, Gut Microbiome, and Clinical Challenges with Alcohol as Confounding Variable.Int J Mol Sci. 2024 Feb 25;25(5):2668. doi: 10.3390/ijms25052668. Int J Mol Sci. 2024. PMID: 38473913 Free PMC article. Review.
-
Role of dietary iron revisited: in metabolism, ferroptosis and pathophysiology of cancer.Am J Cancer Res. 2022 Mar 15;12(3):974-985. eCollection 2022. Am J Cancer Res. 2022. PMID: 35411219 Free PMC article. Review.
-
Hyperferritinemia-A Clinical Overview.J Clin Med. 2021 May 7;10(9):2008. doi: 10.3390/jcm10092008. J Clin Med. 2021. PMID: 34067164 Free PMC article. Review.
-
Revisiting hemochromatosis: genetic vs. phenotypic manifestations.Ann Transl Med. 2021 Apr;9(8):731. doi: 10.21037/atm-20-5512. Ann Transl Med. 2021. PMID: 33987429 Free PMC article. Review.