Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemoglobin and myoglobin are a major source of dietary iron in man. Heme, separated from these hemoproteins by intraluminal proteolysis, is absorbed intact by the intestinal mucosa. The absorbed heme is cleaved in the mucosal cell releasing inorganic iron. Although this mucosal heme-splitting activity initially was ascribed to xanthine oxidase, we investigated the possibility that it is catalyzed by microsomal heme oxygenase, an enzyme which converts heme to bilirubin, CO, and inorganic iron. Microsomes prepared from rat intestinal mucosa contain enzymatic activity similar to that of heme oxygenase in liver and spleen. The intestinal enzyme requires NADPH; is completely inhibited by 50% CO; and produces bilirubin IX-alpha, identified spectrophotometrically and chromatographically. Moreover, duodenal heme oxygenase was shown to release inorganic (55)Fe from (55)Fe-heme. Along the intestinal tract, enzyme activity was found to be highest in the duodenum where hemoglobin iron absorption is reported to be most active. Furthermore, when rats were made iron deficient, duodenal heme oxygenase activity and hemoglobin-iron absorption rose to a comparable extent. Upon iron repletion of iron-deficient animals, duodenal enzyme activity returned towards control values. In contrast to heme oxygenase, duodenal xanthine oxidase activity fell sharply in iron deficiency and rose towards base line upon iron repletion. Our findings suggest that mucosal heme oxygenase catalyzes the cleavage of heme absorbed in the intestinal mucosa and thus plays an important role in the absorption of hemoglobin iron. The mechanisms controlling this intestinal enzyme activity and the enzyme's role in the overall regulation of hemoglobin-iron absorption remain to be defined.
 ...
PMID:Intestinal absorption of hemoglobin iron-heme cleavage by mucosal heme oxygenase. 443 36

We tested the hypothesis proposed by Topham, Woodruff and Walker that intestinal xanthine oxidase is important for iron absorption. We made weanling rats xanthine oxidase-deficient and measured their growth and iron status. There were no significant differences between control and xanthine oxidase-depleted rats in growth or iron absorption or a variety of measures of iron metabolism, except that xanthine oxidase-depleted rats accumulated nonheme iron in the liver. Iron deficiency caused a loss in intestinal xanthine oxidase activity, but also caused an increase in hepatic xanthine oxidase activity. This result may be important for understanding changes in purine and protein metabolism during iron deficiency.
 ...
PMID:Effect of molybdenum-deficient and low iron diets on xanthine oxidase activity and iron status in rats. 654 77

Iron is one of the most important essential metal ions of which significance is well known for ages. This element is a key moiety of several enzymes in iron containing heme or nonheme form and transfer and storage protein, hemoglobin and myoglobin. Several membrane carriers of iron have already been identified. The redox state of iron is determined by xanthine oxidase, cytochromes and Hp or ceruloplasmin and ferroxidase activity of apo-ferritin, respectively. Some vitamins (C, B2-, B3-, B6-, B12) play also a role in the metabolism of iron. The iron content of cells of the organs is well regulated by the iron homeostasis. Iron has a significant role in the immune system by producing oxygen containing free radicals. Anaemia induced by iron deficiency may cause a challenge concerns for pregnant women, babies and adolescent, primarily.
 ...
PMID:[Physiologic and pathologic role of iron in the human body. Iron deficiency anemia in newborn babies]. 1550 4

Iron-sulfur (Fe-S) clusters are small inorganic cofactors formed by tetrahedral coordination of iron atoms with sulfur groups. Present in numerous proteins, these clusters are involved in key biological processes such as electron transfer, metabolic and regulatory processes, DNA synthesis and repair and protein structure stabilization. Fe-S clusters are synthesized mainly in the mitochondrion, where they are directly incorporated into mitochondrial Fe-S cluster-containing proteins or exported for cytoplasmic and nuclear cluster-protein assembly. In this study, we tested the hypothesis that inhibition of mitochondrial complex I by rotenone decreases Fe-S cluster synthesis and cluster content and activity of Fe-S cluster-containing enzymes. Inhibition of complex I resulted in decreased activity of three Fe-S cluster-containing enzymes: mitochondrial and cytosolic aconitases and xanthine oxidase. In addition, the Fe-S cluster content of glutamine phosphoribosyl pyrophosphate amidotransferase and mitochondrial aconitase was dramatically decreased. The reduction in cytosolic aconitase activity was associated with an increase in iron regulatory protein (IRP) mRNA binding activity and with an increase in the cytoplasmic labile iron pool. Since IRP activity post-transcriptionally regulates the expression of iron import proteins, Fe-S cluster inhibition may result in a false iron deficiency signal. Given that inhibition of complex I and iron accumulation are hallmarks of idiopathic Parkinson's disease, the findings reported here may have relevance for understanding the pathophysiology of this disease.
 ...
PMID:Effect of mitochondrial complex I inhibition on Fe-S cluster protein activity. 2157 Sep 52