Potassium zinc chromate hydroxide (T3D0718)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (6)XML
Targets (6)
Record Information
Version2.0
Creation Date2009-03-26 22:04:07 UTC
Update Date2014-12-24 20:22:40 UTC
Accession NumberT3D0718
Identification
Common NamePotassium zinc chromate hydroxide
ClassSmall Molecule
DescriptionPotassium zinc chromate hydroxide is a chemical compound of zinc, potassium and hexavalent chromium. Zinc is a metallic element with the atomic number 30. It is found in nature most often as the mineral sphalerite. Though excess zinc in harmful, in smaller amounts it is an essential element for life, as it is a cofactor for over 300 enzymes and is found in just as many transcription factors. Hexavalent chromium refers to chemical compounds that contain the element chromium in the +6 oxidation state. Chromium(VI) is more toxic than other oxidation states of the chromium atom because of its greater ability to enter cells and higher redox potential. (7, 8, 9)
Compound Type
  • Chromium Compound
  • Industrial/Workplace Toxin
  • Inorganic Compound
  • Pollutant
  • Synthetic Compound
  • Zinc Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Chromic acid, potassium zinc salt (2:2:1)
Potassium hydroxyoctaoxodizincatedichromate(1-)
Potassium zinc chromate
Potassium zinc chromate hydroxide
Potassium zinc chromate hydroxide (KZn2(CrO4)2(OH))
Zinc chromate
Zinc potassium chromate hydroxide
Zinc potassium chromic acid
Zinc yellow
Chemical FormulaCr2HKO9Zn2
Average Molecular Mass418.911 g/mol
Monoisotopic Mass415.665 g/mol
CAS Registry Number11103-86-9
IUPAC Namedizinc(2+) ion potassium bis(dioxochromiumbis(olate)) hydroxide
Traditional Namedizinc(2+) ion potassium bis(chromate(2-)) hydroxide
SMILES[OH-].[K+].[Zn++].[Zn++].[O-][Cr]([O-])(=O)=O.[O-][Cr]([O-])(=O)=O
InChI IdentifierInChI=1S/2Cr.K.H2O.8O.2Zn/h;;;1H2;;;;;;;;;;/q;;+1;;;;;;4*-1;2*+2/p-1
InChI KeyInChIKey=GQKCRUJOPUHISR-UHFFFAOYSA-M
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as miscellaneous chromates. These are inorganic compounds in which the largest metallic oxoanion is chromate, to which either no atom or a non metal atom is bonded.
KingdomInorganic compounds
Super ClassMixed metal/non-metal compounds
ClassMiscellaneous mixed metal/non-metals
Sub ClassMiscellaneous metallic oxoanionic compounds
Direct ParentMiscellaneous chromates
Alternative Parents
Substituents
  • Chromate
  • Alkali metal chromate
  • Inorganic hydride
  • Inorganic oxide
  • Inorganic salt
Molecular FrameworkNot Available
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Endoplasmic reticulum
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Base excision repairNot Availablemap03410
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceGreen-yellow solid.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility10.8 g/LALOGPS
logP-0.3ALOGPS
logP-2.5ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)-2.3ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area80.26 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity5.77 m³·mol⁻¹ChemAxon
Polarizability6.04 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Toxicity Profile
Route of ExposureInhalation (9) ; oral (9) ; dermal (9)
Mechanism of ToxicityAnaemia results from the excessive absorption of zinc suppressing copper and iron absorption, most likely through competitive binding of intestinal mucosal cells. Unbalanced levels of copper and zinc binding to Cu,Zn-superoxide dismutase has been linked to amyotrophic lateral sclerosis (ALS). Stomach acid dissolves metallic zinc to give corrosive zinc chloride, which can cause damage to the stomach lining. Metal fume fever is thought to be an immune response to inhaled zinc. Hexavalent chromium's carcinogenic effects are caused by its metabolites, pentavalent and trivalent chromium. The DNA damage may be caused by hydroxyl radicals produced during reoxidation of pentavalent chromium by hydrogen peroxide molecules present in the cell. Trivalent chromium may also form complexes with peptides, proteins, and DNA, resulting in DNA-protein crosslinks, DNA strand breaks, DNA-DNA interstrand crosslinks, chromium-DNA adducts, chromosomal aberrations and alterations in cellular signaling pathways. It has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases. It can also cause transcriptional repression by cross-linking histone deacetylase 1-DNA methyltransferase 1 complexes to CYP1A1 promoter chromatin, inhibiting histone modification. Chromium may increase its own toxicity by modifying metal regulatory transcription factor 1, causing the inhibition of zinc-induced metallothionein transcription. (1, 7, 2, 3, 4, 8, 9, 5)
MetabolismZinc can enter the body through the lungs, skin, and gastrointestinal tract. Intestinal absorption of zinc is controlled by zinc carrier protein CRIP. Zinc also binds to metallothioneins, which help prevent absorption of excess zinc. Zinc is widely distributed and found in all tissues and tissues fluids, concentrating in the liver, gastrointestinal tract, kidney, skin, lung, brain, heart, and pancreas. In the bloodstream zinc is found bound to carbonic anhydrase in erythrocytes, as well as bound to albumin, _2-macroglobulin, and amino acids in the the plasma. Albumin and amino acid bound zinc can diffuse across tissue membranes. Zinc is excreted in the urine and faeces. Chromium is absorbed from oral, inhalation, or dermal exposure and distributes to nearly all tissues, with the highest concentrations found in kidney and liver. Bone is also a major storage site and may contribute to long-term retention. Hexavalent chromium's similarity to sulfate and chromate allow it to be transported into cells via sulfate transport mechanisms. Inside the cell, hexavalent chromium is reduced first to pentavalent chromium, then to trivalent chromium by many substances including ascorbate, glutathione, and nicotinamide adenine dinucleotide. Chromium is almost entirely excreted with the urine. (1, 7, 9)
Toxicity ValuesNot Available
Lethal Dose1 to 3 grams for an adult human (hexavalent chromium). (6)
Carcinogenicity (IARC Classification)1, carcinogenic to humans. (12)
Uses/SourcesNot Available
Minimum Risk LevelIntermediate Oral: 0.3 mg/kg/day (Zinc) (11) Chronic Oral: 0.3 mg/kg/day (Zinc) (11) Intermediate Oral: 0.005 mg/kg/day (Hexavalent Chromium) (11) Chronic Oral: 0.001 mg/kg/day (Hexavalent Chromium) (11)
Health EffectsChronic exposure to zinc causes anemia, atazia, lethargy, and decreases the level of good cholesterol in the body. It is also believed to cause pancreatic and reproductive damage. Hexavalent chromium is a known carcinogen. Chronic inhalation especially has been linked to lung cancer. Hexavalent chromium has also been know to cause reproductive and developmental defects. (1, 9)
SymptomsIngestion of large doses of zinc causes stomach cramps, nausea, and vomiting. Acute inhalation of large amounts of zinc causes metal fume fever, which is characterized by chills, fever, headache, weakness, dryness of the nose and throat, chest pain, and coughing. Dermal contact with zinc results in skin irritation. Breathing hexavalent chromium can cause irritation to the lining of the nose, nose ulcers, runny nose, and breathing problems, such as asthma, cough, shortness of breath, or wheezing. Ingestion of hexavalent chromium causes irritation and ulcers in the stomach and small intestine, as well as anemia. Skin contact can cause skin ulcers. (7, 9)
TreatmentZinc poisoning is treated symptomatically, often by administering fluids such as water or milk, or with gastric lavage. There is no know antidote for chromium poisoning. Exposure is usually handled with symptomatic treatment. (7, 9)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID25466
ChEMBL IDNot Available
ChemSpider ID23351080
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDZinc potassium chromate
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D0718.pdf
General References
  1. Salnikow K, Zhitkovich A: Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium. Chem Res Toxicol. 2008 Jan;21(1):28-44. Epub 2007 Oct 30. [17970581 ]
  2. Kim G, Yurkow EJ: Chromium induces a persistent activation of mitogen-activated protein kinases by a redox-sensitive mechanism in H4 rat hepatoma cells. Cancer Res. 1996 May 1;56(9):2045-51. [8616849 ]
  3. Schnekenburger M, Talaska G, Puga A: Chromium cross-links histone deacetylase 1-DNA methyltransferase 1 complexes to chromatin, inhibiting histone-remodeling marks critical for transcriptional activation. Mol Cell Biol. 2007 Oct;27(20):7089-101. Epub 2007 Aug 6. [17682057 ]
  4. Kimura T: [Molecular mechanism involved in chromium(VI) toxicity]. Yakugaku Zasshi. 2007 Dec;127(12):1957-65. [18057785 ]
  5. Vonk WI, Klomp LW: Role of transition metals in the pathogenesis of amyotrophic lateral sclerosis. Biochem Soc Trans. 2008 Dec;36(Pt 6):1322-8. doi: 10.1042/BST0361322. [19021549 ]
  6. Barceloux DG: Chromium. J Toxicol Clin Toxicol. 1999;37(2):173-94. [10382554 ]
  7. ATSDR - Agency for Toxic Substances and Disease Registry (2008). Toxicological profile for chromium. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  8. Wikipedia. Zinc. Last Updated 24 March 2009. [Link]
  9. ATSDR - Agency for Toxic Substances and Disease Registry (2005). Toxicological profile for zinc. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  10. Wikipedia. Metallothionein. Last Updated 20 December 2008. [Link]
  11. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  12. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Histone deacetylase 1
General Function:
Transcription regulatory region sequence-specific dna binding
Specific Function:
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation.
Gene Name:
HDAC1
Uniprot ID:
Q13547
Molecular Weight:
55102.615 Da
References
  1. Schnekenburger M, Talaska G, Puga A: Chromium cross-links histone deacetylase 1-DNA methyltransferase 1 complexes to chromatin, inhibiting histone-remodeling marks critical for transcriptional activation. Mol Cell Biol. 2007 Oct;27(20):7089-101. Epub 2007 Aug 6. [17682057 ]
2. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2008). Toxicological profile for chromium. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
Target Details
3. Metal regulatory transcription factor 1
General Function:
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function:
Activates the metallothionein I promoter. Binds to the metal responsive element (MRE).
Gene Name:
MTF1
Uniprot ID:
Q14872
Molecular Weight:
80956.22 Da
References
  1. Kimura T: [Molecular mechanism involved in chromium(VI) toxicity]. Yakugaku Zasshi. 2007 Dec;127(12):1957-65. [18057785 ]
Target Details
4. Mitogen-activated protein kinase 1
General Function:
Rna polymerase ii carboxy-terminal domain kinase activity
Specific Function:
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation.Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.
Gene Name:
MAPK1
Uniprot ID:
P28482
Molecular Weight:
41389.265 Da
References
  1. Kim G, Yurkow EJ: Chromium induces a persistent activation of mitogen-activated protein kinases by a redox-sensitive mechanism in H4 rat hepatoma cells. Cancer Res. 1996 May 1;56(9):2045-51. [8616849 ]
Target Details
5. Mitogen-activated protein kinase 3
General Function:
Phosphatase binding
Specific Function:
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade.
Gene Name:
MAPK3
Uniprot ID:
P27361
Molecular Weight:
43135.16 Da
References
  1. Kim G, Yurkow EJ: Chromium induces a persistent activation of mitogen-activated protein kinases by a redox-sensitive mechanism in H4 rat hepatoma cells. Cancer Res. 1996 May 1;56(9):2045-51. [8616849 ]
Target Details
6. Superoxide dismutase [Cu-Zn]
General Function:
Zinc ion binding
Specific Function:
Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Gene Name:
SOD1
Uniprot ID:
P00441
Molecular Weight:
15935.685 Da
References
  1. Vonk WI, Klomp LW: Role of transition metals in the pathogenesis of amyotrophic lateral sclerosis. Biochem Soc Trans. 2008 Dec;36(Pt 6):1322-8. doi: 10.1042/BST0361322. [19021549 ]