Zinc protoporphyrin: A metabolite with a mission.
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TLDR
Clinically, ZnPP quantification is valuable as a sensitive and specific tool for evaluating iron nutrition and metabolism, and has a potential therapeutic application in controlling bilirubin formation in neonates as a preventive measure for hyperbilirubinemia.Abstract:
Zinc protoporphyrin (ZnPP) is a normal metabolite that is formed in trace amounts during heme biosynthesis. The final reaction in the biosynthetic pathway of heme is the chelation of iron with protoporphyrin. During periods of iron insufficiency or impaired iron utilization, zinc becomes an alternative metal substrate for ferrochelatase, leading to increased ZnPP formation. Evidence suggests that this metal substitution is one of the first biochemical responses to iron depletion, causing increased ZnPP to appear in circulating erythrocytes. Because this zinc-for-iron substitution occurs predominantly within the bone marrow, the ZnPP/heme ratio in erythrocytes reflects iron status in the bone marrow. In addition, ZnPP may regulate heme catabolism through competitive inhibition of heme oxygenase, the rate-limiting enzyme in the heme degradation pathway that produces bilirubin and carbon monoxide. Physiological roles, especially relating to carbon monoxide and possibly nitric oxide production, have been suggested for ZnPP. Clinically, ZnPP quantification is valuable as a sensitive and specific tool for evaluating iron nutrition and metabolism. Diagnostic determinations are applicable in a variety of clinical settings, including pediatrics, obstetrics, and blood banking. ZnPP analytical methodologies for clinical studies are discussed. In addition to diagnostic tests and metabolic studies, ZnPP has a potential therapeutic application in controlling bilirubin formation in neonates as a preventive measure for hyperbilirubinemia. Biochemical research techniques, both in vivo and in vitro, are described for further studies into the role of ZnPP in metabolism and physiology.read more
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Journal ArticleDOI
Biomarkers of Nutrition for Development (BOND)-Iron Review.
Sean Lynch,Christine M. Pfeiffer,Michael K. Georgieff,Gary M. Brittenham,Susan J. Fairweather-Tait,Richard F. Hurrell,Harry J. McArdle,Daniel J Raiten +7 more
TL;DR: A full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers and their interpretation across a range of clinical and population-based uses are provided.
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Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells.
Robert S. Ohgami,Dean R. Campagna,Eric L. Greer,Brendan Antiochos,Alice McDonald,Jing Chen,Jing Chen,Jing Chen,John J. Sharp,John J. Sharp,Yuko Fujiwara,Jane E. Barker,Mark D. Fleming +12 more
TL;DR: Findings indicate that Steap3 is an endosomal ferrireductase required for efficient Tf-dependent iron uptake in erythroid cells.
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Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase
Christian Frezza,Liang Zheng,Ori Folger,Kartik N. Rajagopalan,Elaine D. MacKenzie,Livnat Jerby,Massimo Micaroni,Barbara Chaneton,Julie Adam,Ann Hedley,Gabriela Kalna,Ian Tomlinson,Patrick J. Pollard,Dave Watson,Ralph J. DeBerardinis,Tomer Shlomi,Eytan Ruppin,Eyal Gottlieb +17 more
TL;DR: This work predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh2-containing cells, and demonstrated that inhibition of haem oxygenation is synthetically lethal when combined with Fh 1 deficiency.
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Diagnosis and management of iron-deficiency anaemia
TL;DR: The optimal diagnostic approach is to measure the serum ferritin as an index of iron stores and the serum transferrin receptor as a index of tissue iron deficiency.
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Metal preferences and metallation.
TL;DR: The metal binding preferences of most metalloproteins do not match their metal requirements, and metallation of an estimated 30% of metalloenzymes is aided by metal delivery systems, with ∼25% acquiring preassembled metal cofactors.
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