Zinc protoporphyrin

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Zinc protoporphyrin
ZnPPIX L.svg
Names
Other names
Zinc protoporphyrin IX
Identifiers
ChEBI
ECHA InfoCard 100.035.853 OOjs UI icon edit-ltr-progressive.svg
KEGG
MeSH zinc+protoporphyrin
PubChem CID
UNII
Properties
C34H32N4O4Zn
Molar mass 626.032 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Zinc protoporphyrin (ZPP) refers to coordination complexes of zinc and protoporphyrin IX. It is a red-purple solid that is soluble in water. The complex and related species are found in red blood cells when heme production is inhibited by lead and/or by lack of iron. [1]

Contents

Clinical utility

Measurement of zinc protoporphyrin in red cells has been used for screening for lead poisoning. [2] [3] and for iron deficiency. [4] [1] [5]

Zinc protoporphyrin levels can be elevated as the result of a number of conditions, for instance: [2]

The virtue of elevated 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. [7]

ZnPP is finding a new use as a drug in combined cancer therapies.

History

Porphyrin complexes of zinc have been known since the 1930s. [1] In 1974 ZPP was identified as a major non-heme porphyrin formed in red cells as the result of lead poisoning or iron deficiency., [8] It was already known at this time that non-heme protoporphyrin IX levels were elevated in these conditions, but prior investigators had used acidic extraction methods in their assays that converted ZPP to unbound Protoporphyrin IX. [9] The early literature on quantifying zinc-PP levels may be unreliable. [1] [4]

For cancer therapy

ZnPP has been investigated for cancer therapies. [10] [11] [12]

ZnPP is a competitive inhibitor of heme oxygenase. [12] Heme oxygenase is a cytoprotective enzyme that copes with oxidative stress on a cell and shows higher expression in cancerous tissues. [13] ZnPP suppression of heme oxygenase reduces cell viability of cancer cells and increases cytotoxicity in cancer cells. [13] ZnPP works in combination with anticancer drugs to increase cytotoxicity. [14] ZnPP inhibits tumor growth especially solid tumors. [14] Tumors from brain cancer, colon cancer, prostate cancer, renal cell cancer, oral squamous cell cancer, and leukemia all show a susceptibility to ZnPP due to increase expression of heme oxygenase. [14] The inhibition of heme oxygenase leads to an increase of reactive oxidative species in the cell which sensitizes the cells to chemotherapeutic agents. [10] Increased reactive oxidative species can cause apoptosis in cancer cells and reduce drug resistance when exposed to ZnPP due to loss of the heme oxygenase coping mechanism. [14] The combination of these two therapies is highly effective in treating cancer in experiments thus far, and is a possible new method for overcoming drug resistance. The reduced coping ability of tissues treated with ZnPP also increases radiosensitivity. [15] Cells treated with ZnPP and radiation as opposed to simply one of the two are less viable and more likely to stay in G1 phase of the cell cycle, rather than progress to the G2 phase. [15] ZnPP and radiation combination therapy shows more apoptosis than the same amount of radiation displaying that ZnPP puts stress on cancerous tissue. [15] ZnPP have been injected in a number of trials on solid tumors, but can be utilized more broadly when effectively delivered to cancer cells and not healthy cells. [10] A targeted delivery system is needed to fully exploit the uses of ZnPP as a therapeutic agent and heme oxygenase inhibitor due to the potential side effects of free ZnPP on healthy tissue. [10] Reducing the anti-oxidant capability of healthy cells can reduce effects that would have been favorable. [10] However ZnPP have been encapsulated in nanoparticles with specialized coating for drug delivery inside the body. [10] ZnPP did not show any reduce inhibitory potential on heme oxygenase when loaded into nanoparticles. [10] Similarly ZnPP loaded into nanoparticles has a higher cytotoxicity than free ZnPP after two days due to a more favorable release rate as well as better biodistribution and internalization. [10] The possible negative effects on major organs were not seen and blood distribution is more desirable in ZnPP loaded nanoparticles than free ZnPP. [10] The specific inhibition of heme oxygenase using nanoparticles with encapsulated ZnPP reduces side effects and is likely the future method of administering ZnPP treatment. [10]

Structural chemistry

Zinc porphyrins are always five- or six-coordinate. Because the axial ligands are labile, these complexes are often depicted with planar structures. Planar zinc(II) complexes are unknown.

Related Research Articles

<span class="mw-page-title-main">Heme</span> Chemical coordination complex of an iron ion chelated to a porphyrin

Heme, or haem, is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.

<span class="mw-page-title-main">Iron deficiency</span> State in which a body lacks enough iron to supply its needs

Iron deficiency, or sideropenia, is the state in which a body lacks enough iron to supply its needs. Iron is present in all cells in the human body and has several vital functions, such as carrying oxygen to the tissues from the lungs as a key component of the hemoglobin protein, acting as a transport medium for electrons within the cells in the form of cytochromes, and facilitating oxygen enzyme reactions in various tissues. Too little iron can interfere with these vital functions and lead to morbidity and death.

<span class="mw-page-title-main">Porphyrin</span> Heterocyclic organic compound with four modified pyrrole subunits

Porphyrins are a group of heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (=CH−). In vertebrates, an essential member of the porphyrin group is heme, which is a component of hemoproteins, whose functions include carrying oxygen in the bloodstream. In plants, an essential porphyrin derivative is chlorophyll, which is involved in light harvesting and electron transfer in photosynthesis.

<span class="mw-page-title-main">Porphyria cutanea tarda</span> Medical condition

Porphyria cutanea tarda is the most common subtype of porphyria. The disease is named because it is a porphyria that often presents with skin manifestations later in life. The disorder results from low levels of the enzyme responsible for the fifth step in heme production. Heme is a vital molecule for all of the body's organs. It is a component of hemoglobin, the molecule that carries oxygen in the blood.

<span class="mw-page-title-main">Erythropoietic protoporphyria</span> Medical condition

Erythropoietic protoporphyria is a form of porphyria, which varies in severity and can be very painful. It arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the red blood cells (erythrocytes), plasma, skin, and liver. The severity varies significantly from individual to individual.

<span class="mw-page-title-main">Aminolevulinic acid</span> Endogenous non-proteinogenic amino acid

δ-Aminolevulinic acid, an endogenous non-proteinogenic amino acid, is the first compound in the porphyrin synthesis pathway, the pathway that leads to heme in mammals, as well as chlorophyll in plants.

<span class="mw-page-title-main">Iron-deficiency anemia</span> Medical condition

Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, short of breath, or having decreased ability to exercise. Anemia that comes on quickly often has more severe symptoms, including confusion, feeling like one is going to pass out or increased thirst. Anemia is typically significant before a person becomes noticeably pale. Children with iron deficiency anemia may have problems with growth and development. There may be additional symptoms depending on the underlying cause.

<span class="mw-page-title-main">Gunther disease</span> Medical condition

Gunther disease is a congenital form of erythropoietic porphyria. The word porphyria originated from the Greek word porphura. Porphura actually means "purple pigment", which, in suggestion, the color that the body fluid changes when a person has Gunther's disease. It is a rare, autosomal recessive metabolic disorder affecting heme, caused by deficiency of the enzyme uroporphyrinogen cosynthetase. It is extremely rare, with a prevalence estimated at 1 in 1,000,000 or less. There have been times that prior to birth of a fetus, Gunther's disease has been shown to lead to anemia. In milder cases patients have not presented any symptoms until they have reached adulthood. In Gunther's disease, porphyrins are accumulated in the teeth and bones and an increased amount are seen in the plasma, bone marrow, feces, red blood cells, and urine.

<span class="mw-page-title-main">Sideroblastic anemia</span> Medical condition

Sideroblastic anemia, or sideroachrestic anemia, is a form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes). In sideroblastic anemia, the body has iron available but cannot incorporate it into hemoglobin, which red blood cells need in order to transport oxygen efficiently. The disorder may be caused either by a genetic disorder or indirectly as part of myelodysplastic syndrome, which can develop into hematological malignancies.

<span class="mw-page-title-main">Heme oxygenase</span>

Heme oxygenase, or haem oxygenase, is an enzyme that catalyzes the degradation of heme to produce biliverdin, ferrous ion, and carbon monoxide.

<span class="mw-page-title-main">Ferrochelatase</span>

Protoporphyrin ferrochelatase (EC 4.98.1.1, formerly EC 4.99.1.1, or ferrochelatase; systematic name protoheme ferro-lyase (protoporphyrin-forming)) is an enzyme encoded by the FECH gene in humans. Ferrochelatase catalyses the eighth and terminal step in the biosynthesis of heme, converting protoporphyrin IX into heme B. It catalyses the reaction:

Erythropoietic porphyria is a type of porphyria associated with erythropoietic cells. In erythropoietic porphyrias, the enzyme deficiency occurs in the red blood cells.

<span class="mw-page-title-main">Protoporphyrin IX</span> Chemical compound

Protoporphyrin IX is an organic compound, classified as a porphyrin, that plays an important role in living organisms as a precursor to other critical compounds like heme (hemoglobin) and chlorophyll. It is a deeply colored solid that is not soluble in water. The name is often abbreviated as PPIX.

<span class="mw-page-title-main">Radiosensitizer</span>

A radiosensitizer is an agent that makes tumor cells more sensitive to radiation therapy. It is sometimes also known as a radiation sensitizer or radio-enhancer.

<span class="mw-page-title-main">Sonodynamic therapy</span>

Sonodynamic therapy (SDT) is a noninvasive treatment, often used for tumor irradiation, that utilizes a sonosensitizer and the deep penetration of ultrasound to treat lesions of varying depths by reducing target cell number and preventing future tumor growth. Many existing cancer treatment strategies cause systemic toxicity or cannot penetrate tissue deep enough to reach the entire tumor; however, emerging ultrasound stimulated therapies could offer an alternative to these treatments with their increased efficiency, greater penetration depth, and reduced side effects. Sonodynamic therapy could be used to treat cancers and other diseases, such as atherosclerosis, and diminish the risk associated with other treatment strategies since it induces cytotoxic effects only when externally stimulated by ultrasound and only at the cancerous region, as opposed to the systemic administration of chemotherapy drugs.

<span class="mw-page-title-main">Carbon monoxide-releasing molecules</span> Substances delivering CO within the body

Carbon monoxide-releasing molecules (CORMs) are chemical compounds designed to release controlled amounts of carbon monoxide (CO). CORMs are being developed as potential therapeutic agents to locally deliver CO to cells and tissues, thus overcoming limitations of CO gas inhalation protocols.

Haem or Heme carrier protein 1 (HCP1) was originally identified as mediating heme-Fe transport although it later emerged that it was the SLC46A1 folate transporter.

<span class="mw-page-title-main">Gold nanoparticles in chemotherapy</span> Drug delivery technique using gold nanoparticles as vectors

Gold nanoparticles in chemotherapy and radiotherapy is the use of colloidal gold in therapeutic treatments, often for cancer or arthritis. Gold nanoparticle technology shows promise in the advancement of cancer treatments. Some of the properties that gold nanoparticles possess, such as small size, non-toxicity and non-immunogenicity make these molecules useful candidates for targeted drug delivery systems. With tumor-targeting delivery vectors becoming smaller, the ability to by-pass the natural barriers and obstacles of the body becomes more probable. To increase specificity and likelihood of drug delivery, tumor specific ligands may be grafted onto the particles along with the chemotherapeutic drug molecules, to allow these molecules to circulate throughout the tumor without being redistributed into the body.

Iron preparation is the formulation for iron supplements indicated in prophylaxis and treatment of iron-deficiency anemia. Examples of iron preparation include ferrous sulfate, ferrous gluconate, and ferrous fumarate. It can be administered orally, and by intravenous injection, or intramuscular injection.

<span class="mw-page-title-main">Tin mesoporphyrin</span> Compound in biochemistry

Tin mesoporphyrin (SnMP), also known as stannsoporfin, is a synthetic metalloporphyrin, which consists of a group of competitive inhibitors of heme oxygenase, a rate-limiting enzyme in the heme catabolic pathway. Tin mesoporphyrin is one of the more potent metalloporphyrin compound out of all the others.

References

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