Gliotoxin
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Basic Info
| Common Name | Gliotoxin(F04878) |
| 2D Structure | |
| Description | Gliotoxin is a sulfur-containing antibiotic produced by several species of fungi, some of which are pathogens of humans such as Aspergillus, and also by species of Trichoderma, and Penicillium. Gliotoxin possesses immunosuppressive properties as it may suppress and cause apoptosis in certain types of cells of the immune system, including neutrophils, eosinophils, granulocytes, macrophages, and thymocytes. (L1941) |
| FRCD ID | F04878 |
| CAS Number | 67-99-2 |
| PubChem CID | 6223 |
| Formula | C13H14N2O4S2 |
| IUPAC Name | None |
| InChI Key | FIVPIPIDMRVLAY-RBJBARPLSA-N |
| InChI | InChI=1S/C13H14N2O4S2/c1-14-10(18)12-5-7-3-2-4-8(17)9(7)15(12)11(19)13(14,6-16)21-20-12/h2-4,8-9,16-17H,5-6H2,1H3/t8-,9-,12+,13+/m0/s1 |
| Canonical SMILES | CN1C(=O)C23CC4=CC=CC(C4N2C(=O)C1(SS3)CO)O |
| Isomeric SMILES | CN1C(=O)[C@]23CC4=CC=C[C@@H]([C@H]4N2C(=O)[C@]1(SS3)CO)O |
| Wikipedia | Gliotoxin |
| Synonyms |
gliotoxin
67-99-2
Aspergillin
UNII-5L648PH06K
CCRIS 4025
Gliotoxin from Gliocladium fimbriatum
NSC 102866
BRN 0050675
AI3-62383
CHEBI:5385
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organoheterocyclic compounds |
| Class | Diazinanes |
| Subclass | Piperazines |
| Intermediate Tree Nodes | Dioxopiperazines - 2,5-dioxopiperazines - Thiodioxopiperazines - Epipolythiodioxopiperazines |
| Direct Parent | Gliotoxins |
| Alternative Parents |
|
| Molecular Framework | Aliphatic heteropolycyclic compounds |
| Substituents | Gliotoxin-skeleton - Alpha-amino acid or derivatives - Indole or derivatives - N-alkylpiperazine - N-methylpiperazine - Dithiazinane - Tertiary carboxylic acid amide - Pyrrolidine - Carboxamide group - Lactam - Organic disulfide - Secondary alcohol - Carboxylic acid derivative - Azacycle - Organonitrogen compound - Hydrocarbon derivative - Organic oxide - Organopnictogen compound - Alcohol - Organic oxygen compound - Carbonyl group - Organic nitrogen compound - Organooxygen compound - Primary alcohol - Aliphatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as gliotoxins. These are polycyclic compounds containing the gliotoxin skeleton, which is structurally characterized by a epipolythiodioxopiperazine moiety fused to the pyrrolidine ring of an indol-7-ol derivative. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 326.385 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 1 |
| Complexity | 621 |
| Monoisotopic Mass | 326.039 |
| Exact Mass | 326.039 |
| XLogP | -0.7 |
| Formal Charge | 0 |
| Heavy Atom Count | 21 |
| Defined Atom Stereocenter Count | 4 |
| 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- | 0.7509 |
| Human Intestinal Absorption | HIA- | 0.5000 |
| Caco-2 Permeability | Caco2- | 0.5967 |
| P-glycoprotein Substrate | Substrate | 0.7144 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8771 |
| Non-inhibitor | 0.8445 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.6917 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.5981 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7912 |
| CYP450 2D6 Substrate | Non-substrate | 0.8203 |
| CYP450 3A4 Substrate | Substrate | 0.5730 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.7229 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.6673 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8572 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.7174 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8511 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.6994 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9893 |
| Non-inhibitor | 0.8251 | |
| AMES Toxicity | Non AMES toxic | 0.9132 |
| Carcinogens | Non-carcinogens | 0.8939 |
| Fish Toxicity | High FHMT | 0.8372 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.7220 |
| Honey Bee Toxicity | Low HBT | 0.5000 |
| Biodegradation | Not ready biodegradable | 0.7650 |
| Acute Oral Toxicity | III | 0.5146 |
| Carcinogenicity (Three-class) | Non-required | 0.5677 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.7067 | LogS |
| Caco-2 Permeability | 0.7638 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.8183 | LD50, mol/kg |
| Fish Toxicity | 1.2800 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.4395 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| [The contamination and dietary exposure analysis for seven mycotoxins in theFifth Chinese Total Diet Study]. | Zhonghua Yu Fang Yi Xue Za Zhi | 2017 Oct 6 | 29036999 |
| Aspergillosis, a Natural Infection in Poultry: Mycological and Molecular Characterization and Determination of Gliotoxin in Aspergillus fumigatus Isolates. | Avian Dis | 2017 Mar | 28301237 |
| Role of mycotoxins in the pathobiology of autism: A first evidence. | Nutr Neurosci | 2017 Aug 10:1-13 | 28795659 |
| Ecophysiology of environmental Aspergillus fumigatus and comparison with clinical strains on gliotoxin production and elastase activity. | Lett Appl Microbiol | 2016 Feb | 26551056 |
| A new approach using micro HPLC-MS/MS for multi-mycotoxin analysis in maize samples. | Mycotoxin Res | 2015 May | 25759213 |
| Comparison of toxicogenic and immunosuppressive capacity of Aspergillus fumigatus strains isolated from clinical and corn silage samples. | J Appl Microbiol | 2015 Jan | 25346380 |
| Review on Mycotoxin Issues in Ruminants: Occurrence in Forages, Effects of Mycotoxin Ingestion on Health Status and Animal Performance and Practical Strategies to Counteract Their Negative Effects. | Toxins (Basel) | 2015 Aug 12 | 26274974 |
| Gliotoxin production by Aspergillus fumigatus strains from animal environment. Micro-analytical sample treatment combined with a LC-MS/MS method for gliotoxin determination. | Mycotoxin Res | 2015 Aug | 25982450 |
| Physiological behaviour of gliotoxigenic Aspergillus fumigatus sensu stricto isolated from maize silage under simulated environmental conditions. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2015 | 25599419 |
| GliA in Aspergillus fumigatus is required for its tolerance to gliotoxin and affects the amount of extracellular and intracellular gliotoxin. | Med Mycol | 2014 Jul | 24847038 |
| Gliotoxinogenic Aspergillus fumigatus in the dairy herd environment. | Mycotoxin Res | 2013 May | 23467846 |
| Typing clinical and animal environment Aspergillus fumigatus gliotoxin producer strains isolated from Brazil by PCR-RFLP markers. | Lett Appl Microbiol | 2013 Dec | 23889550 |
| Natural co-occurrence of fungi and mycotoxins in poultry feeds from Entre Ríos, Argentina. | Food Addit Contam Part B Surveill | 2013 | 24779900 |
| Gβ-like CpcB plays a crucial role for growth and development of Aspergillus nidulans and Aspergillus fumigatus. | PLoS One | 2013 | 23936193 |
| Method for identifying heat-resistant fungi of the genus Neosartorya. | J Food Prot | 2012 Oct | 23043829 |
| Survey of Aspergillus and Fusarium species and their mycotoxins in raw materials and poultry feeds from Córdoba, Argentina. | Mycotoxin Res | 2012 May | 23606049 |
| Gliotoxin contamination in and pre- and postfermented corn, sorghum and wet brewer's grains silage in Sao Paulo and Rio de Janeiro State, Brazil. | J Appl Microbiol | 2012 May | 22372472 |
| Multi-mycotoxin analysis of maize silage by LC-MS/MS. | Anal Bioanal Chem | 2010 May | 20213172 |
| Aspergillus fumigatus toxicity and gliotoxin levels in feedstuff for domestic animals and pets in Argentina. | Lett Appl Microbiol | 2010 Jan | 19889107 |
| Mycoflora and mycotoxin production in oilseed cakes during farm storage. | J Agric Food Chem | 2009 Feb 25 | 19183000 |
Targets
- General Function:
- Zinc ion binding
- Specific Function:
- Essential subunit of the farnesyltransferase complex. Catalyzes the transfer of a farnesyl moiety from farnesyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X.
- Gene Name:
- FNTB
- Uniprot ID:
- P49356
- Molecular Weight:
- 48773.2 Da
- Mechanism of Action:
- Gliotoxin inhibits the enzyme farnesyl-protein transferase.
References
- Van der Pyl D, Inokoshi J, Shiomi K, Yang H, Takeshima H, Omura S: Inhibition of farnesyl-protein transferase by gliotoxin and acetylgliotoxin. J Antibiot (Tokyo). 1992 Nov;45(11):1802-5. [1281813 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. Known substrates include RAC1, RAC2, RAP1A and RAP1B.
- Gene Name:
- PGGT1B
- Uniprot ID:
- P53609
- Molecular Weight:
- 42367.81 Da
References
- Vigushin DM, Brooke G, Willows D, Coombes RC, Moody CJ: Pyrazino[1,2-a]indole-1,4-diones, simple analogues of gliotoxin, as selective inhibitors of geranylgeranyltransferase I. Bioorg Med Chem Lett. 2003 Nov 3;13(21):3661-3. [14552752 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. Also weakly methylates histone H1 (in vitro). H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes, such as repression of MYOD1-stimulated differentiation, regulation of the control switch for exiting the cell cycle and entering differentiation, repression by the PML-RARA fusion protein, BMP-induced repression, repression of switch recombination to IgA and regulation of telomere length. Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Recruited by the large PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation.
- Gene Name:
- SUV39H1
- Uniprot ID:
- O43463
- Molecular Weight:
- 47907.065 Da
References
- Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
- General Function:
- Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
- Specific Function:
- NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer.
- Gene Name:
- NFKB2
- Uniprot ID:
- Q00653
- Molecular Weight:
- 96748.355 Da
- Mechanism of Action:
- Gliotoxin specifically inhibits transcription factor NF-kappaB, causing immunosuppressive effects.
References
- Pahl HL, Krauss B, Schulze-Osthoff K, Decker T, Traenckner EB, Vogt M, Myers C, Parks T, Warring P, Muhlbacher A, Czernilofsky AP, Baeuerle PA: The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kappaB. J Exp Med. 1996 Apr 1;183(4):1829-40. [8666939 ]
- General Function:
- Rab geranylgeranyltransferase activity
- Specific Function:
- Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. Contributes to the transfer of a farnesyl or geranylgeranyl moiety from farnesyl or geranylgeranyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. May positively regulate neuromuscular junction development downstream of MUSK via its function in RAC1 prenylation and activation.
- Gene Name:
- FNTA
- Uniprot ID:
- P49354
- Molecular Weight:
- 44408.32 Da
- Mechanism of Action:
- Gliotoxin inhibits the enzyme farnesyl-protein transferase.
References
- Van der Pyl D, Inokoshi J, Shiomi K, Yang H, Takeshima H, Omura S: Inhibition of farnesyl-protein transferase by gliotoxin and acetylgliotoxin. J Antibiot (Tokyo). 1992 Nov;45(11):1802-5. [1281813 ]
- General Function:
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function:
- Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
- Gene Name:
- SLC22A11
- Uniprot ID:
- Q9NSA0
- Molecular Weight:
- 59970.945 Da
- Mechanism of Action:
- Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity.
References
- Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
- General Function:
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function:
- Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-independent uptake of p-aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid (By similarity). PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate.
- Gene Name:
- SLC22A6
- Uniprot ID:
- Q4U2R8
- Molecular Weight:
- 61815.78 Da
- Mechanism of Action:
- Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity.
References
- Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
- General Function:
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function:
- Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha-ketoglutarate.
- Gene Name:
- SLC22A7
- Uniprot ID:
- Q9Y694
- Molecular Weight:
- 60025.025 Da
- Mechanism of Action:
- Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity.
References
- Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.
- Gene Name:
- EHMT2
- Uniprot ID:
- Q96KQ7
- Molecular Weight:
- 132369.205 Da
References
- Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
- General Function:
- Secondary active organic cation transmembrane transporter activity
- Specific Function:
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
- Gene Name:
- SLC22A1
- Uniprot ID:
- O15245
- Molecular Weight:
- 61153.345 Da
- Mechanism of Action:
- Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity.
References
- Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
- General Function:
- Quaternary ammonium group transmembrane transporter activity
- Specific Function:
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
- Gene Name:
- SLC22A2
- Uniprot ID:
- O15244
- Molecular Weight:
- 62579.99 Da
- Mechanism of Action:
- Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity.
References
- Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
- General Function:
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function:
- Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
- Gene Name:
- SLC22A8
- Uniprot ID:
- Q8TCC7
- Molecular Weight:
- 59855.585 Da
- Mechanism of Action:
- Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity.
References
- Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]