Zinc protoporphyrin: A metabolite with a mission.

Zinc protoporphyrin: A metabolite with a mission.
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DOI:
10.1093/clinchem/45.12.2060
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发表时间:
1999-12
期刊:
影响因子:
9.3
通讯作者:
R. Labbé;H. Vreman;D. K. Stevenson
R. Labbé;H. Vreman;D. K. Stevenson
中科院分区:
医学1区
文献类型:
--
作者:
R. Labbé;H. Vreman;D. K. Stevenson

文献摘要

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锌原卟啉(ZnPP)是血红素生物合成过程中形成的一种微量的正常代谢产物。血红素生物合成途径中的最后反应是铁与原卟啉的螯合。在铁不足或铁利用受损期间,锌成为亚铁螯合酶的替代金属底物,导致ZnPP形成增加。有证据表明,这种金属替代是对铁缺乏的第一个生化反应之一,导致ZnPP增加出现在循环红细胞中。因为这种锌对铁的替代主要发生在骨髓中,所以红细胞中的ZnPP/血红素比反映了骨髓中的铁状态。此外,ZnPP可以通过竞争性抑制血红素加氧酶(产生胆红素和一氧化碳的血红素降解途径中的限速酶)来调节血红素分解代谢。生理作用,特别是涉及一氧化碳和可能的一氧化氮的生产,已被建议为ZnPP。在临床上,ZnPP定量作为评价铁营养和代谢的敏感和特异性工具是有价值的。诊断测定适用于各种临床环境,包括儿科、产科和血库。ZnPP分析方法的临床研究进行了讨论。除了诊断试验和代谢研究外,ZnPP在控制新生儿胆红素形成方面具有潜在的治疗应用,可作为高胆红素血症的预防措施。生物化学的研究技术,在体内和体外,被描述为进一步研究锌PP在代谢和生理学中的作用。
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.