Zinc protoporphyrin
Encyclopedia
Zinc protoporphyrin is a compound found in red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...

s when heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...

 production is inhibited by lead and/or by lack of iron
Iron deficiency (medicine)
Iron deficiency is one of the most common of the nutritional deficiencies. Iron is present in all cells in the human body, and has several vital functions...

.
Instead of incorporating a ferrous ion, to form heme, protoporphyrin IX
Protoporphyrin IX
Protoporphyrin IX, in the metabolism of porphyrin, is created by the enzyme protoporphyrinogen oxidase.-Heme b biosynthesis:In heme biosynthesis, the enzyme ferrochelatase converts it into heme b Protoporphyrin IX, in the metabolism of porphyrin, is created by the enzyme protoporphyrinogen...

, the immediate precursor of heme, incorporates a zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...

 ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...

, forming ZPP. The reaction to insert a ferrous ion into protoporphyrin IX is catalyzed by the enzyme ferrochelatase
Ferrochelatase
Ferrochelatase is an enzyme that catalyses the terminal step in the biosynthesis of heme, converting protoporphyrin IX into heme. It catalyses the reaction:A ferrochelatase enzyme consists of 497 amino acid residues with a m.w...

.

Clinical utility

Measurement of zinc protoporphyrin in red cells has been used as a screening test for lead poisoning.
and for iron deficiency
Iron deficiency (medicine)
Iron deficiency is one of the most common of the nutritional deficiencies. Iron is present in all cells in the human body, and has several vital functions...

.
There are a number of specific clinical situations in which this measurement has been found to be useful.

Zinc protoporphyrin levels can be elevated as the result of a number of conditions, for instance:
  • lead poisoning
  • iron deficiency
  • sickle cell anemia
  • sideroblastic anemia
  • anemia of chronic disease
  • vanadium exposure

The virtue of ZPP testing as a screen is that all of these conditions can be considered worth discovering.

The fluorescent properties of ZPP in intact red cells allows the ZPP/heme molar ratio to be measured quickly, at low cost, and in a small sample volume.

History

Porphyrin compounds containing zinc have been known since the 1930s. They became of more than academic interest with the discovery, in 1974, that ZPP was the major non-heme porphyrin formed in red cells as the result of lead poisoning or iron deficiency.

It was already known at this time that non-heme Protoporphyrin IX levels were elevated in these conditions, but prior investigators had used extraction methods that converted ZPP to unbound Protoporphyrin IX.

The early literature is sometimes confusing, and results are hard to compare without detailed examination of the measurement methods and the conversion factors used to report the results. Reports may refer to Free Erythrocyte Protoporphyrin (FEP) or Erythrocyte Protoporphyrin (EP or EPP). ZPP is also abbreviated ZP and ZnPP. Current practice is tending to measure and report the molar ratio of ZPP to Heme (μmole/mole).
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