Zinc Protoporphyrin and Iron Deficient Erythropoiesis

Garrett, Sally; Worwood, Mark

doi:10.1159/000204238

Cited by 34 publications

(12 citation statements)

References 4 publications

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“…Because this phenotype is not normally observed in cells, it is reasonable to extrapolate from the present work that iron control of heme biosynthesis is a general regulatory phenomenon found in other organisms. Humans with iron deficiency anemia show a 5-fold increase in blood protoporphyrin, reaching approximately 2 ϫ 10 Ϫ4 mol/ mol of heme (38). This elevated level is modest by comparison with the B. japonicum irr mutant, which accumulates approximately 15 mol of protoporphyrin/mol of heme under iron limitation (by recalculation of the data in Fig.…”

Section: Discussionmentioning

confidence: 99%

The Bacterial Irr Protein Is Required for Coordination of Heme Biosynthesis with Iron Availability

Hamza

Chauhan²,

Hassett

et al. 1998

Journal of Biological Chemistry

150

198

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Heme is a ubiquitous macromolecule that serves as the active group of proteins involved in many cellular processes. The multienzyme pathway for heme formation culminates with the insertion of iron into a protoporphyrin ring. The cytotoxicity of porphyrins suggests the need for coordination of its biosynthesis with iron availability. We isolated a mutant strain of the bacterium Bradyrhizobium japonicum that, under iron limitation, accumulated protoporphyrin and showed aberrantly high expression of hemB, an iron-regulated gene encoding the heme synthesis enzyme ␦-aminolevulinic acid dehydratase. The strain carries a loss of function mutation in irr, a newly described gene that encodes a putative member of the GntR family of bacterial transcriptional regulators. Irr accumulated only under iron limitation, and turned over rapidly upon an increase in iron availability. A separate role for Irr in controlling the cellular iron level was inferred based on a deficiency in high affinity iron transport activity in the irr strain, and suggests that regulation of the heme pathway is coordinated with iron homeostasis. A high level of protoporphyrin accumulation is not a normal consequence of nutritional iron deprivation, thus a mechanism for iron-dependent control of heme biosynthesis may be present in other organisms.

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Section: Discussionmentioning

confidence: 99%

The Bacterial Irr Protein Is Required for Coordination of Heme Biosynthesis with Iron Availability

Hamza

Chauhan²,

Hassett

et al. 1998

Journal of Biological Chemistry

150

198

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“…When ZPP is measured in whole blood, falsely elevated values are observed in dialysis patients as well as in the presence of bilirubin and various drugs. Removing these interferences requires careful washing of the RBCs, rendering this assay inappropriate for routine clinical care 172,173 . Erythrocyte ZPP is elevated in the presence of lead poisoning.…”

Section: Erythrocyte Zinc Protoporphyrinmentioning

confidence: 99%

Diagnosis of iron-deficient states

Archer

Brugnara

2015

Critical Reviews in Clinical Laboratory Sciences

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The diagnosis of iron deficiency anemia is typically straightforward, especially when classic biochemical and hematological changes are present in a subject at risk. It can be challenging in the presence of diseases or when it is due to inherited defects of iron metabolism. The identification of iron deficiency prior to anemia development is also difficult. New hematological parameters such as reticulocyte Hb content have expanded the classic ones such as MCV, MCH and MCHC. A variety of hematology analyzers now provide novel parameters to assess cellular hypochromia and microcytosis in both reticulocytes and mature red blood cells. The repertoire of biochemical markers has also been expanded, with iron, transferrin and ferritin being supplemented by circulating transferrin receptor and hepcidin. Molecular identification of functional variants of key iron metabolism determinants has provided explanations for the heritability of some iron metabolism biomarkers. Genetic defects in some of these molecules are responsible for hereditary microcytic anemias, also called atypical microcytic anemias. In this review, we examine the most significant hematological and biochemical markers for iron metabolism, as well as relevant genetic polymorphisms and defects affecting iron handling.

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“…A problem with fluorimetric measurement of ZPP arises from the presence of fluorescent compounds in plasma, and values obtained on washed cells are almost always lower than those on whole blood 30. The proportional differences between paired measurements found in this study were similar to those reported elsewhere in subjects free of disorders associated with spuriously raised whole blood ZPP values,30 indicating that most if not all raised values were genuine, including those found in children with proven or probable α-thalassaemia trait. As expected, the plasma effect was greatest in the iron-sufficient group, which had the lowest ZPP values, and least in the iron deficiency anaemia group.…”

Section: Discussionmentioning

confidence: 99%

An assessment of methods used in the investigation of iron status: findings in a population of young British South Asian children

2015

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Among 205 British South Asian children aged 4-43 months with high incidences of anaemia, iron deficiency, infection and α-thalassaemia, 151 (73.6%) were classified using haemoglobin, MCH, ferritin and CRP values. In 42 non-anaemic, iron-sufficient children with subnormal MCH values, that is with a phenotype of α-thalassaemia trait, RDW, %hypo and ZPP values did not differ significantly from those with iron-deficient erythropoiesis. Raised RDW, %hypo and ZPP values should be interpreted with caution in non-anaemic young British South Asian children with microcytosis.

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Zinc Protoporphyrin and Iron Deficient Erythropoiesis

Cited by 34 publications

References 4 publications

The Bacterial Irr Protein Is Required for Coordination of Heme Biosynthesis with Iron Availability

The Bacterial Irr Protein Is Required for Coordination of Heme Biosynthesis with Iron Availability

Diagnosis of iron-deficient states

An assessment of methods used in the investigation of iron status: findings in a population of young British South Asian children

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