Chromium
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Basic Info
Common Name | Chromium(F03330) |
2D Structure | |
Description | Chromium is a naturally occurring heavy metal found in the environment commonly in trivalent, Cr(III), and hexavalent, Cr(VI), forms. The reduction of Cr(VI) to Cr(III) results in the formation of reactive intermediates that contribute to the cytotoxicity, genotoxicity and carcinogenicity of Cr(VI)-containing compounds. The major non-occupational source of chromium for humans is food such as vegetables, meat, urban air, hip or knee prostheses and cigarettes. Cr(VI) is a widely used in industrial chemicals, extensively used in paints, metal finishes, steel including stainless steel manufacturing, alloy cast irons, chrome and wood treatment. On the contrary, Cr(III) salts such as chromium polynicotinate, chromium chloride and chromium picolinate (CrP) are used as micronutrients and nutritional supplements and have been demonstrated to exhibit a significant number of health benefits in animals and humans. Physiologically, it exists as an ion in the body. Chromium enters the body through the lungs, gastro-intestinal tract and to a lesser extent through skin. Inhalation is the most important route for occupational exposure, whereas non-occupational exposure occurs via ingestion of chromium-containing food and water. Regardless of route of exposure Cr(III) is poorly absorbed whereas Cr(VI) is more readily absorbed. Further, absorption of Cr(VI) is poorer by oral route, it is thus not very toxic when introduced by the oral route. But chromium is very toxic by dermal and inhalation routes and causes lung cancer, nasal irritation, nasal ulcer, hypersensitivity reactions and contact dermatitis. All the ingested Cr(VI) is reduced to Cr(III) before entering in the blood stream. The main routes for the excretion of chromium are via kidney/urine and the bile/feces. Cr(III) is unable to enter into the cells but Cr(VI) enters through membrane anionic transporters. Intracellular Cr(VI) is metabolically reduced to Cr(III). Cr(VI) does not react with macromolecules such as DNA, RNA, proteins and lipids. However, both Cr(III) and the reductional intermediate Cr(V) are capable of co-ordinate, covalent interactions with macromolecules. Chromium is an essential nutrient required by the human body to promote the action of insulin for the utilization of sugars, proteins and fats. CrP has been used as nutritional supplement; it controls blood sugar in diabetes and may reduce cholesterol and blood pressure levels. Chromium increases insulin binding to cells, insulin receptor number and activates insulin receptor kinase leading to increased insulin sensitivity. But high doses of chromium and long term exposure of it can give rise to various, cytotoxic and genotoxic reactions that affect the immune system of the body. However, the mechanism of the Cr(VI)-induced cytotoxicity is not entirely understood. A series of in vitro and in vivo studies have demonstrated that Cr(VI) induces oxidative stress through enhanced production of reactive oxygen species (ROS) leading to genomic DNA damage and oxidative deterioration of lipids and proteins. A cascade of cellular events occur following Cr(VI)-induced oxidative stress including enhanced production of superoxide anion and hydroxyl radicals, increased lipid peroxidation and genomic DNA fragmentation, modulation of intracellular oxidized states, activation of protein kinase C, apoptotic cell death and altered gene expression. Some of the factors in determining the biological outcome of chromium exposure include the bioavailability, solubility of chromium compounds and chemical speciation, intracellular reduction and interaction with DNA. The chromium genotoxicity manifests as several types of DNA lesions, gene mutations and inhibition of macromolecular synthesis. Further, chromium exposure may lead to apoptosis, premature terminal growth arrest or neoplastic transformation. Chromium-induced tumor suppressor gene p53 and oxidative processes are some of the major factors that may determine the cellular outcome. Studies have utilized these approaches to understand the interrelationship between chromium-induced genotoxicity, apoptosis and effects on immune response. (A7701). |
FRCD ID | F03330 |
CAS Number | 7440-47-3 |
PubChem CID | 23976 |
Formula | Cr |
IUPAC Name | chromium |
InChI Key | VYZAMTAEIAYCRO-UHFFFAOYSA-N |
InChI | InChI=1S/Cr |
Canonical SMILES | [Cr] |
Isomeric SMILES | [Cr] |
Wikipedia | Chromium |
Synonyms | Chromium metal Chromium 7440-47-3 Chrom Chrome Chromium compounds cromo Chrome [French] Chrom [German] Chromium, elemental |
Classifies | Pollutant Metal |
Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
Kingdom | Inorganic compounds |
Superclass | Homogeneous metal compounds |
Class | Homogeneous transition metal compounds |
Subclass | Not available |
Intermediate Tree Nodes | Not available |
Direct Parent | Homogeneous transition metal compounds |
Alternative Parents | |
Molecular Framework | Not available |
Substituents | Homogeneous transition metal |
Description | This compound belongs to the class of inorganic compounds known as homogeneous transition metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a transition metal atom. |
Properties
Property Name | Property Value |
---|---|
Molecular Weight | 51.996 |
Hydrogen Bond Donor Count | 0 |
Hydrogen Bond Acceptor Count | 0 |
Rotatable Bond Count | 0 |
Complexity | 0 |
Monoisotopic Mass | 51.941 |
Exact Mass | 51.941 |
Formal Charge | 0 |
Heavy Atom Count | 1 |
Defined Atom Stereocenter Count | 0 |
Undefined Atom Stereocenter Count | 0 |
Defined Bond Stereocenter Count | 0 |
Undefined Bond Stereocenter Count | 0 |
Isotope Atom Count | 0 |
Covalently-Bonded Unit Count | 1 |
ADMET
Model | Result | Probability |
---|---|---|
Absorption | ||
Blood-Brain Barrier | BBB+ | 0.9733 |
Human Intestinal Absorption | HIA+ | 0.9838 |
Caco-2 Permeability | Caco2+ | 0.7354 |
P-glycoprotein Substrate | Non-substrate | 0.8810 |
P-glycoprotein Inhibitor | Non-inhibitor | 0.9787 |
Non-inhibitor | 0.9858 | |
Renal Organic Cation Transporter | Non-inhibitor | 0.9108 |
Distribution | ||
Subcellular localization | Lysosome | 0.5856 |
Metabolism | ||
CYP450 2C9 Substrate | Non-substrate | 0.8466 |
CYP450 2D6 Substrate | Non-substrate | 0.8259 |
CYP450 3A4 Substrate | Non-substrate | 0.8158 |
CYP450 1A2 Inhibitor | Non-inhibitor | 0.8809 |
CYP450 2C9 Inhibitor | Non-inhibitor | 0.9373 |
CYP450 2D6 Inhibitor | Non-inhibitor | 0.9708 |
CYP450 2C19 Inhibitor | Non-inhibitor | 0.9554 |
CYP450 3A4 Inhibitor | Non-inhibitor | 0.9880 |
CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8820 |
Excretion | ||
Toxicity | ||
Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9547 |
Non-inhibitor | 0.9746 | |
AMES Toxicity | Non AMES toxic | 0.9633 |
Carcinogens | Carcinogens | 0.6640 |
Fish Toxicity | Low FHMT | 0.6181 |
Tetrahymena Pyriformis Toxicity | Low TPT | 0.6631 |
Honey Bee Toxicity | High HBT | 0.8315 |
Biodegradation | Ready biodegradable | 0.7326 |
Acute Oral Toxicity | III | 0.5846 |
Carcinogenicity (Three-class) | Warning | 0.4769 |
Model | Value | Unit |
---|---|---|
Absorption | ||
Aqueous solubility | -1.0958 | LogS |
Caco-2 Permeability | 1.6017 | LogPapp, cm/s |
Distribution | ||
Metabolism | ||
Excretion | ||
Toxicity | ||
Rat Acute Toxicity | 2.0135 | LD50, mol/kg |
Fish Toxicity | 1.5413 | pLC50, mg/L |
Tetrahymena Pyriformis Toxicity | -0.7156 | pIGC50, ug/L |
References
Title | Journal | Date | Pubmed ID |
---|---|---|---|
Evaluation of chemical extractants to assess metals phytoavailability in Brazilian municipal solid waste composts. | Environ Pollut | 2018 Sep 21 | 30267920 |
Concentration of heavy metals in seafood (fishes, shrimp, lobster and crabs) and human health assessment in Saint Martin Island, Bangladesh. | Ecotoxicol Environ Saf | 2018 Sep 15 | 29747150 |
Source identification and spatial distribution of arsenic and heavy metals inagricultural soil around Hunan industrial estate by positive matrix factorizationmodel, principle components analysis and geo statistical analysis. | Ecotoxicol Environ Saf | 2018 Sep 15 | 29778047 |
Biomass decaying and elemental release of aquatic macrophyte detritus inwaterways of the Indian River Lagoon basin, South Florida, USA. | Sci Total Environ | 2018 Sep 1 | 29710610 |
Heavy metal and microbial safety assessment of raw and cooked pumpkin and <i>Amaranthus viridis</i> leaves grown in Abakaliki, Nigeria. | Food Sci Nutr | 2018 Sep | 30258596 |
Patterns of toxic metals bioaccumulation in a cross-border freshwater reservoir. | Chemosphere | 2018 Sep | 29800819 |
Nickel and associated metals in New Caledonia: Exposure levels and theirdeterminants. | Environ Int | 2018 Sep | 29864722 |
Rice flakes produced from commercial wild rice: Chemical compositions, vitamin B compounds, mineral and trace element contents and their dietary intake evaluation. | Food Chem | 2018 Oct 30 | 29853391 |
High-density element concentrations in fish from subtidal to hadal zones of the Pacific Ocean. | Heliyon | 2018 Oct | 30320235 |
Risk assessment for potentially toxic metal(loid)s in potatoes in the indigenous zinc smelting area of northwestern Guizhou Province, China. | Food Chem Toxicol | 2018 Oct | 30016697 |
Chromium uptake by lettuce as affected by the application of organic matter and Cr(VI)-irrigation water: Implications to the land use and water management. | Chemosphere | 2018 Nov | 30031343 |
Impacts of ultramafic outcrops in Peninsular Malaysia and Sabah on soil and waterquality. | Environ Monit Assess | 2018 May 8 | 29737421 |
Probiotic mitigates the toxic effects of potassium dichromate in a preclinical study: a randomized controlled trial. | J Sci Food Agric | 2018 May 30 | 29851070 |
Influence of Chronic Toxicity, Lipid Metabolism, Learning and Memory Ability, and Related Enzyme in Sprague-Dawley Rats by Long-Term Chromium Malate Supplementation. | Biol Trace Elem Res | 2018 May 24 | 29797207 |
Prevalence of elevated blood lead levels among pregnant women and sources of leadexposure in rural Bangladesh: A case control study. | Environ Res | 2018 May 24 | 29804028 |
Assessment of metal levels in foodstuffs from the Region of Valencia (Spain). | Toxicol Rep | 2018 May 21 | 30003045 |
Analysis and Risk Assessment of Seven Toxic Element Residues in Raw Bovine Milk in China. | Biol Trace Elem Res | 2018 May | 28825229 |
Environmental Exposure of Children to Toxic Trace Elements (Hg, Cr, As) in an Urban Area of Yucatan, Mexico: Water, Blood, and Urine Levels. | Bull Environ Contam Toxicol | 2018 May | 29508017 |
Trace elements in seafood from the Mediterranean sea: An exposure riskassessment. | Food Chem Toxicol | 2018 May | 29510219 |
[Biological significance of chromium III for the human organism]. | Med Pr | 2018 Mar 9 | 29035404 |
Targets
- 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
- Mechanism of Action:
- Chromium has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases.
References
- 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 ]
- General Function:
- Transferrin receptor binding
- Specific Function:
- Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation.
- Gene Name:
- TF
- Uniprot ID:
- P02787
- Molecular Weight:
- 77063.195 Da
References
- Moshtaghie AA, Ani M, Bazrafshan MR: Comparative binding study of aluminum and chromium to human transferrin. Effect of iron. Biol Trace Elem Res. 1992 Jan-Mar;32:39-46. [1375080 ]
- 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
- Mechanism of Action:
- Chromium may increase its own toxicity by modifying metal regulatory transcription factor 1, causing the inhibition of zinc-induced metallothionein transcription.
References
- Kimura T: [Molecular mechanism involved in chromium(VI) toxicity]. Yakugaku Zasshi. 2007 Dec;127(12):1957-65. [18057785 ]
- 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
- Mechanism of Action:
- Chromium can cause transcriptional repression by cross-linking histone deacetylase 1-DNA methyltransferase 1 complexes to CYP1A1 promoter chromatin, inhibiting histone modification.
References
- 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 ]
- 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
- Mechanism of Action:
- Chromium has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases.
References
- 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 ]