Effect of altered iron metabolism on markers of haem biosynthesis and intestinal iron absorption in mice.
In this study, well-characterised animal models of altered iron metabolism were used to investigate link(s) between haem biosynthesis and intestinal iron absorption. Mice rendered iron deficient by feeding a low-iron diet for 3-4 weeks showed low levels of hepatic non-haem iron and hepcidin mRNA, with reduced urinary 5-aminolaevulinic acid (ALA) excretion and enhanced intestinal iron absorption. Hepatic ALA synthase activity was reduced while ALA dehydratase activity was increased. Iron-loaded mice had markedly increased liver non-haem iron and hepcidin mRNA, with increased urinary ALA excretion. Intestinal iron absorption was decreased mainly due to a reduction in transfer of absorbed iron from mucosa to the carcass. Hepatic ALA synthase activity was increased and ALA dehydratase activity moderately reduced. Mice exposed to hypoxia (0.5 atm) for 1-3 days had reduced hepatic hepcidin mRNA and urinary ALA excretion, while intestinal iron absorption was increased. Hepatic ALA synthase activity was reduced. The ALA dehydratase activity in liver and spleen was markedly enhanced. Injection of ALA to iron-deficient mice or hypoxic mice reduced their intestinal iron absorption to normal levels. This study further supports the hypothesis that alterations in haem biosynthesis influence duodenal iron absorption. ALA in particular appears to function as a modulator in controlling intestinal iron absorption.
Laftah
A H
AH
Department of Life Sciences, King's College, Franklin Wilkins Building, Stamford Street, London, SE1 9NN, UK. abas.h.laftah@kcl.ac.uk
Raja
K B
KB
Latunde-Dada
G O
GO
Vergi
T
T
McKie
A T
AT
Simpson
R J
RJ
Peters
T J
TJ
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000494:pharmacology / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004386:Duodenum / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis*; D000860:Hypoxia; D007408:Intestinal Absorption; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D019189:Iron Metabolism Disorders / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D000623:Porphobilinogen Synthase / Q000378:metabolism
D015415:Biomarkers; D006418:Heme; D000622:Aminolevulinic Acid; D007501:Iron; D000624:5-Aminolevulinate Synthetase; D000623:Porphobilinogen Synthase