Isotopic evidence of unaccounted for Fe and Cu erythropoietic pathways

Abstract

Despite its potential importance for understanding perturbations in the Fe-Cu homeostatic pathways, the natural isotopic variability of these metals in the human body remains unexplored. We measured the Fe, Cu, and Zn isotope compositions of total blood, serum, and red blood cells of ~50 young blood donors by multiple-collector ICP-MS after separation and purification by anion exchange chromatography. Zinc shows much less overall isotopic variability than Fe and Cu, which indicates that isotope fractionation depends more on redox conditions than on ligand coordination. On average, Fe in erythrocytes is isotopically light with respect to serum, whereas Cu is heavy. Iron and Cu isotope compositions clearly separate erythrocytes of men and women. Fe and Cu from B-type men erythrocytes are visibly more fractionated than all the other blood types. Isotope compositions provide an original method for evaluating metal mass balance and homeostasis. Natural isotope variability shows that the current models of Fe and Cu erythropoiesis violate mass balance requirements. It unveils unsuspected major pathways for Fe, with erythropoietic production of isotopically heavy ferritin and hemosiderin, and for Cu, with isotopically light Cu being largely channeled into blood and lymphatic circulation rather than into superoxide dismutase-laden erythrocytes. Iron isotopes provide an intrinsic measuring rod of the erythropoietic yield, while Cu isotopes seem to gauge the relative activity of erythropoiesis and lymphatics.

An iron stable isotope comparison between human erythrocytes and plasma

“…Hence, redox processes play the decisive role in iron isotope fractionation between compartments of the human body, regardless of whether the pathways are direct or indirect. 1,13 Conclusions A chemical separation procedure using microwave treatment and anion exchange chromatography was developed for analysis of iron isotopes in human blood plasma by MC-ICP-MS. The isotope composition of plasma is exceedingly sensitive to hemolysis which may occur during blood sampling and subsequent centrifugation.…”

“…To date, only one study has reported the iron composition of human blood plasma and found it to be enriched in 56 Fe over 54 Fe relative to blood, and hence being of composition closer to liver iron. 13 In this study we test these hypotheses by presenting precise iron stable isotope ratios measured in human erythrocytes and plasma samples. Blood was sampled over a period of 21 days from 12 healthy male adults.…”

Natural variations of copper and sulfur stable isotopes in blood of hepatocellular carcinoma patients

“…Cu ratio, expressed in delta units (Method), varies between organs from −1‰ in liver to +1‰ in kidney (6) (for comparison, this ratio ranges from −3‰ to +2.5‰ in terrestrial materials). In humans, the 65 Cu/ 63 Cu ratio in blood and bone differs between men and women (7,8), partly because a sizeable proportion of the women's blood copper comes from the liver to balance menstrual losses (9,10). The body 65 Cu/ 63 Cu ratio varies according to that of diet (11) and also seems to be age dependent (12).…”

The Iron Stable Isotope Fingerprint of the Human Diet

“…10 % for non-heme iron 1 . To take this effect into account, we weigh the mean diets isotope composition by these efficiencies and the iron consumption ( 4 an average δ 56 Fe of -2.74 ± 0.16 ‰ for 22 males and -2.57 ± 0.19 ‰ for 25 females. The average of all samples from these three studies is -2.76 ± 0.18 ‰ for males and -2.50 ± 0.20 ‰ for females from which we obtained a fractionation factor for intestinal absorption of -1.3 ‰ for female omnivores and -2.0 ‰ for female vegetarians.…”