Iron acquisition is critical for virulence of the human pathogenic fungus Cryptococcus neoformans. The cryptococcal transcript for the extracellular mannoprotein Cig1 is highly regulated by iron and abundant in iron-starved cells, suggesting a role in iron acquisition. Indeed, loss of Cig1 resulted in delayed growth on heme at physiological pH. Expression of CIG1 is regulated by the pH-responsi...

Adult humans have about 25 trillion red blood cells (RBCs), and each second we recycle about 5 million RBCs by erythrophagocytosis (EP) in macrophages of the reticuloendothelial system. Despite the central role for EP in mammalian iron metabolism, the molecules and pathways responsible for heme trafficking during EP remain unknown. Here, we show that the mammalian homolog of HRG1, a transmembra...

BACKGROUND Calcium is the only reported dietary inhibitor of both heme- and nonheme-iron absorption. It has been proposed that the 2 forms of iron enter a common pool in the enterocyte and that calcium inhibits the serosal transfer of iron into blood. OBJECTIVES We aimed to ascertain whether the inhibitory effect of calcium occurs during initial mucosal uptake or during serosal transfer and t...

Plesiomonas shigelloides is a gram-negative pathogen which can utilize heme as an iron source. In previous work, P. shigelloides genes which permitted heme iron utilization in a laboratory strain of Escherichia coli were isolated. In the present study, the cloned P. shigelloides sequences were found to encode ten potential heme utilization proteins: HugA, the putative heme receptor; TonB and Ex...

The Bradyrhizobium japonicum transcriptional regulator Irr (iron response regulator) is a key regulator of the iron homeostasis, which is degraded in response to heme binding via a mechanism that involves oxidative modification of the protein. Here, we show that heme-bound Irr activates O2 to form highly reactive oxygen species (ROS) with the "active site conversion" from heme iron to non-heme ...

In iron deficiency, zinc protoporphyrin (ZPP) is produced instead of heme, and the ZPP concentration in erythrocytes is increased (normal < or = 40 mumol/mol heme). We investigated the relevance of ZPP for staging iron deficiency. ZPP was determined by hematofluorometry in samples from 103 patients. Nineteen patients with iron depletion showed decreased serum ferritin (12.1 +/- 4.4 micrograms/L...

Mitochondria are responsible for the synthesis of both iron-sulfur clusters and heme, but the potential connection between the two major iron-consuming pathways is unknown. Here, we have shown that mutants in the yeast mitochondrial iron-sulfur cluster (ISC) assembly machinery displayed reduced cytochrome levels and diminished activity of the heme-containing cytochrome c oxidase, in addition to...

Utilization of heme by bacteria as a nutritional iron source involves the transport of exogenous heme, followed by cleavage of the heme macrocycle to release iron. Bradyrhizobium japonicum can use heme as an iron source, but no heme-degrading oxygenase has been described. Here, bioinformatics analyses of the B. japonicum genome identified two paralogous genes renamed hmuQ (bll7075) and hmuD (bl...

The reaction of protoporphyrin with iron to form heme is usually studied in intact or lysed cells in the presence of salts of ionic iron. Despite the fact that such iron is utilized for heme synthesis, the form of iron available to erythropoietic cells in the intact animal is that which is present in serum in the form of a highly stable iron-protein complex, transferrin. Results obtained by use...

BACKGROUND The effect of bariatric surgery on iron absorption is only partially known. OBJECTIVE The objective was to study the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) on heme- and nonheme-iron absorption and iron status. DESIGN Fifty-eight menstruating women were enrolled in this prospective study [mean (±SD) age: 35.9 ± 9.1 y; weight: 101.7 ± 13.5 kg; BMI (...