Isopimaric acid

Isopimaric acid
Names
	IUPAC name (13S)-Pimara-7,15-dien-18-oic acid
	Systematic IUPAC name (1R,4aR,4bS,7S,10aR)-7-Ethenyl-1,4a,7-trimethyl-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodecahydrophenanthrene-1-carboxylic acid
Identifiers
CAS Number	5835-26-7 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:6039 ;
ChEMBL	ChEMBL512164 ;
ChemSpider	390596 ;
ECHA InfoCard	100.163.144
KEGG	C09118 ;
PubChem CID	442048;
UNII	1E37K85HHK ;
CompTox Dashboard (EPA)	DTXSID9022233 ;
	InChI InChI=1S/C20H30O2/c1-5-18(2)12-9-15-14(13-18)7-8-16-19(15,3)10-6-11-20(16,4)17(21)22/h5,7,15-16H,1,6,8-13H2,2-4H3,(H,21,22)/t15-,16+,18-,19+,20+/m0/s1 Key: MXYATHGRPJZBNA-KRFUXDQASA-N ; InChI=1/C20H30O2/c1-5-18(2)12-9-15-14(13-18)7-8-16-19(15,3)10-6-11-20(16,4)17(21)22/h5,7,15-16H,1,6,8-13H2,2-4H3,(H,21,22)/t15-,16+,18-,19+,20+/m0/s1 Key: MXYATHGRPJZBNA-KRFUXDQABR;
	SMILES [H][C@]12[C@](C)(C(O)=O)CCC[C@]1(C)[C@]3([H])C(C[C@](C=C)(C)CC3)=CC2;
Properties
Chemical formula	C20H30O2
Molar mass	302.458 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Isopimaric acid (IPA) is a toxin which acts as a large conductance Ca²⁺-activated K⁺ channel (BK channel) opener.

Sources

IPA originates from many sorts of trees, especially conifers.^[1]

Chemistry

IPA is one of the members of the resin acid group and it is a tricyclic diterpene.^[1]

Target

IPA acts on the large-conductance calcium activated K+ channels (BK channels).^[2]^[3]

Mode of action

BK channels are formed by α subunits and accessory β subunits arranged in tetramers. The α subunit forms the ion conduction pore and the β subunit contributes to channel gating. IPA interaction with the BK channel enhances Ca²⁺ and / or voltage sensitivity of the α subunit of BK channels without affecting the channel conductance. In this state BK channels can still be inhibited by one of their inhibitors, like charybdotoxin (CTX).^[2]^[3] Opening of the BK channel leads to an increased K⁺-efflux which hyperpolarizes the resting membrane potential, reducing the excitability of the cell in which the BK-channel is expressed.

Toxicity

Studies on rainbow trout hepatocytes have shown that IPA increases intracellular calcium release, leading to a disturbance in the calcium homeostasis. This could be important in the possible toxicity of the toxin.

Notes

^ ^a ^b Wilson, AE; Moore, ER; Mohn, WW (1996). "Isolation and characterization of isopimaric acid-degrading bacteria from a sequencing batch reactor". Applied and Environmental Microbiology. 62 (9): 3146–51. Bibcode:1996ApEnM..62.3146W. doi:10.1128/aem.62.9.3146-3151.1996. PMC 168108. PMID 8795202.
^ ^a ^b Kaczorowski, GJ; Knaus, HG; Leonard, RJ; McManus, OB; Garcia, ML (1996). "High-conductance calcium-activated potassium channels; structure, pharmacology, and function". Journal of Bioenergetics and Biomembranes. 28 (3): 255–67. doi:10.1007/bf02110699. PMID 8807400. S2CID 25857254.
^ ^a ^b Imaizumi, Y; Sakamoto, K; Yamada, A; Hotta, A; Ohya, S; Muraki, K; Uchiyama, M; Ohwada, T (2002). "Molecular basis of pimarane compounds as novel activators of large-conductance Ca(2+)-activated K(+) channel alpha-subunit". Molecular Pharmacology. 62 (4): 836–46. doi:10.1124/mol.62.4.836. PMID 12237330.

References

Råbergh, Christina M.I.; Lilius, Henrik; Eriksson, John E.; Isomaa, Boris (1999). "The resin acids dehydroabietic acid and isopimaric acid release calcium from intracellular stores in rainbow trout hepatocytes". Aquatic Toxicology. 46: 55–65. doi:10.1016/S0166-445X(98)00115-5.
Råbergh, C.M.I.; Isomaa, B.; Eriksson, J.E. (1992). "The resin acids dehydroabietic acid and isopimaric acid inhibit bile acid uptake and perturb potassium transport in isolated hepatocvtes from rainbow trout (Oncorhynchus mykiss)". Aquatic Toxicology. 23 (3–4): 169–179. doi:10.1016/0166-445X(92)90050-W.

[Wilson-1] Wilson, AE; Moore, ER; Mohn, WW (1996). "Isolation and characterization of isopimaric acid-degrading bacteria from a sequencing batch reactor". Applied and Environmental Microbiology. 62 (9): 3146–51. Bibcode:1996ApEnM..62.3146W. doi:10.1128/aem.62.9.3146-3151.1996. PMC 168108. PMID 8795202.

[Kaczorowski-2] Kaczorowski, GJ; Knaus, HG; Leonard, RJ; McManus, OB; Garcia, ML (1996). "High-conductance calcium-activated potassium channels; structure, pharmacology, and function". Journal of Bioenergetics and Biomembranes. 28 (3): 255–67. doi:10.1007/bf02110699. PMID 8807400. S2CID 25857254.

[Imaizumi-3] Imaizumi, Y; Sakamoto, K; Yamada, A; Hotta, A; Ohya, S; Muraki, K; Uchiyama, M; Ohwada, T (2002). "Molecular basis of pimarane compounds as novel activators of large-conductance Ca(2+)-activated K(+) channel alpha-subunit". Molecular Pharmacology. 62 (4): 836–46. doi:10.1124/mol.62.4.836. PMID 12237330.

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