Record Information
Version 1.0
Creation Date 2010-05-10 10:23:41 -0600
Update Date 2014-08-11 10:36:20 -0600
Accession Number T3D3746
Identification
Common Name Territrem A
Description Territrem A is a tremorgenic mycotoxin found in the fungus Aspergillus terreus, which has been know to contaminate rice crops. Tremorgenic mycotoxins affect central nervous system activity, with their defining characteristic being the tremors that they cause. Territrems induce this effect by inhibiting the enzyme acetylcholinesterase in peripheral nerve endings. (A3028, A3029)
Compound Type
  • Organic Compound
  • Mycotoxin
Chemical Structure
Thumb
Synonyms
  1. 4H,11H-Naphtho(2,1-b)pyrano(3,4-e)pyran-1,11(5H)-dione, 4a,6,6a,12,12a,12b-hexahydro-4a,12a-dihydroxy-9-(7-methoxy-1,3-benzodioxo-5-yl)-4,4,6a,12b-tetramethyl-, (4aR,6aR,12aS,12bS)-
  2. 4H,11H-Naphtho(2,1-b)pyrano(3,4-e)pyran-1,11(5H)-dione, 4a,6,6a,12,12a,12b-hexahydro-4a,12a-dihydroxy-9-(7-methoxy-1,3-benzodioxo-5-yl)-4,4,6a,12b-tetramethyl-, (4aR-(4a-alpha,6a-beta,12a-alpha,12b-beta))-
Chemical Formula C28H30O9
Average Molecular Weight 510.5324
Monoisotopic Molecular Weight 510.188982558
IUPAC Name
7a,11b-dihydroxy-3-(7-methoxy-2H-1,3-benzodioxol-5-yl)-5a,8,8,11a-tetramethyl-1,5a,6,7,7a,8,11,11a,11b,12-decahydro-2,5-dioxatetraphene-1,11-dione
Traditional IUPAC Name
7a,11b-dihydroxy-3-(7-methoxy-2H-1,3-benzodioxol-5-yl)-5a,8,8,11a-tetramethyl-7,12-dihydro-6H-2,5-dioxatetraphene-1,11-dione
CAS Registry Number 70407-19-1
SMILES
COC1=CC(=CC2=C1OCO2)C1=CC2=C(CC3(O)C(C)(CCC4(O)C(C)(C)C=CC(=O)C34C)O2)C(=O)O1
InChI Identifier
InChI=1S/C28H30O9/c1-24(2)7-6-21(29)26(4)27(24,31)9-8-25(3)28(26,32)13-16-18(37-25)12-17(36-23(16)30)15-10-19(33-5)22-20(11-15)34-14-35-22/h6-7,10-12,31-32H,8-9,13-14H2,1-5H3
InChI Key InChIKey=LCJHAHVVYAVVPA-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Heterocyclic Compounds
Class Naphthopyrans
Sub Class Not Available
Direct Parent Naphthopyrans
Alternative Parents
  • Naphthalenes
  • Benzodioxoles
  • Anisoles
  • Cyclohexanols
  • Pyranones and Derivatives
  • Alkyl Aryl Ethers
  • Tertiary Alcohols
  • Cyclic Alcohols and Derivatives
  • Ketones
  • Cycloalkenes
  • Acetals
Molecular Framework Aromatic Heteropolycyclic Compounds
Substituents
  • benzene
  • naphthalene
  • cycloalkene
  • phenol ether
  • anisole
  • alkyl aryl ether
  • ketone
  • acene
  • benzodioxole
  • cyclohexanol
  • cyclic alcohol
  • acetal
  • alcohol
  • tertiary alcohol
  • pyran
  • pyranone
External Descriptors Not Available
Biological Properties
Status Unknown/Not Detected
Origin Not Available
Cellular Locations Not Available
Biofluid Locations Not Available
Tissue Locations Not Available
Pathways Not Available
Physical Properties
State Not Available
Appearance Not Available
Experimental Properties
Property Value
Melting Point Not Available
Boiling Point Not Available
Solubility Not Available
LogP Not Available
Predicted Properties
PropertyValueSource
water solubility2.53e-02 g/lALOGPS
logP2.3ALOGPS
logP2.44ChemAxon
logS-4.3ALOGPS
pKa (strongest acidic)5.5ChemAxon
pKa (strongest basic)-3.4ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count8ChemAxon
hydrogen donor count2ChemAxon
polar surface area120.75ChemAxon
rotatable bond count2ChemAxon
refractivity133.18ChemAxon
polarizability53.42ChemAxon
Spectra
Spectra Not Available
Toxicity Profile
Route of Exposure Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101)
Mechanism of Toxicity Territrems act at the peripheral nerve endings as irreversible inhibitors of acetylcholinesterase. As acetylcholinesterase is needed to hydrolyze the neurotransmitter acetylcholine in cholinergic synapses, inhibition of this enzyme continually potentiates the acetylcholine-induced current of the neuron. It is thought that territrems inhibits acetylcholinesterase by becoming noncovalently trapped within the unique active-site gorge structure of the enzyme. (A3028, A3029)
Metabolism The biotransformation of territrems involves hydroxylation and 0-demethylation. Metabolism is performed by cytochrome P-450 monooxygenases in the liver, with CYP3A4 and CYP3A5 being the major enzymes used. (A3028, A3030)
Toxicity Values Not Available
Lethal Dose Not Available
Carcinogenicity (IARC Classification) Not Available
Uses/Sources Territrem A is a tremorgenic mycotoxin found in the fungus Aspergillus terreus. (A3028)
Minimum Risk Level Not Available
Health Effects Tremorgenic mycotoxins affect central nervous system activity. They cause a neurological disease of cattle known as "staggers syndrome". (A2976)
Symptoms Tremorgenic mycotoxins affect central nervous system activity, inducing neurologic symptoms including mental confusion, paralysis, tremors, seizures, and death. They cause a neurological disease of cattle known as "staggers syndrome", which is characterized by muscle tremors and hyperexcitability. (A2976)
Treatment To control severe tremorscaused by tremorgenic mycotoxins, methocarbamol should be administered. Generalized seizures may be treated with diazepam followed by methocarbamol or a barbiturate such as pentobarbital sodium. Gastric lavage should be performed and activated charcoal administered to limit further absorption of toxins. (T318)
Normal Concentrations
Not Available
DrugBank ID Not Available
HMDB ID Not Available
PubChem Compound ID 115079
ChEMBL ID Not Available
ChemSpider ID Not Available
KEGG ID Not Available
UniProt ID Not Available
OMIM ID Not Available
ChEBI ID Not Available
BioCyc ID Not Available
CTD ID Not Available
Stitch ID Not Available
PDB ID Not Available
ACToR ID Not Available
Wikipedia Link Not Available
References
General References
  • A2974 — Valdes JJ, Cameron JE, Cole RJ: Aflatrem: a tremorgenic mycotoxin with acute neurotoxic effects. Environ Health Perspect. 1985 Oct;62:459-63. [2867895 ]
  • A2976 — Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
  • A3028 — Ling KH, Chiou CM, Tseng YL: Biotransformation of territrems by S9 fraction from rat liver. Drug Metab Dispos. 1991 May-Jun;19(3):587-95. [1680623 ]
  • A3029 — Chen JW, Luo YL, Hwang MJ, Peng FC, Ling KH: Territrem B, a tremorgenic mycotoxin that inhibits acetylcholinesterase with a noncovalent yet irreversible binding mechanism. J Biol Chem. 1999 Dec 3;274(49):34916-23. [10574966 ]
  • A3030 — Peng FC, Chang CC, Yang CY, Edwards RJ, Doehmer J: Territrems B and C metabolism in human liver microsomes: major role of CYP3A4 and CYP3A5. Toxicology. 2006 Feb 1;218(2-3):172-85. Epub 2005 Dec 5. [16337070 ]
  • A3101 — Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
  • T318 — Schell MM. Tremorgenic mycotoxin intoxication. Veterinary Medicine. 2000.

Targets

1. Acetylcholinesterase

Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.

Territrems act at the peripheral nerve endings as irreversible inhibitors of acetylcholinesterase. As acetylcholinesterase is needed to hydrolyze the neurotransmitter acetylcholine in cholinergic synapses, inhibition of this enzyme continually potentiates the acetylcholine-induced current of the neuron. It is thought that territrems inhibits acetylcholinesterase by becoming noncovalently trapped within the unique active-site gorge structure of the enzyme. (A3028, A3029)
UniProt ID: P22303
Gene: ACHE
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A3028 — Ling KH, Chiou CM, Tseng YL: Biotransformation of territrems by S9 fraction from rat liver. Drug Metab Dispos. 1991 May-Jun;19(3):587-95. [1680623 ]
  • A3029 — Chen JW, Luo YL, Hwang MJ, Peng FC, Ling KH: Territrem B, a tremorgenic mycotoxin that inhibits acetylcholinesterase with a noncovalent yet irreversible binding mechanism. J Biol Chem. 1999 Dec 3;274(49):34916-23. [10574966 ]