Cyclopiazonic acid

Cyclopiazonic acid
Names
	Preferred IUPAC name (6aR,11aS,11bR)-10-Acetyl-11-hydroxy-7,7-dimethyl-2,6,6a,7,11a,11b-hexahydro-9H-pyrrolo[1′,2′:2,3]isoindolo[4,5,6-cd]indol-9-one
Identifiers
CAS Number	18172-33-3 ;
3D model (JSmol)	Interactive image;
Beilstein Reference	707309
ChEBI	CHEBI:22450 ;
ChEMBL	ChEMBL480627 ;
ChemSpider	21106432 ;
ECHA InfoCard	100.162.058
EC Number	634-041-6;
IUPHAR/BPS	5350;
KEGG	C03032;
PubChem CID	65261;
UNII	X9TLY4580Z ;
CompTox Dashboard (EPA)	DTXSID00891798 ;
	InChI InChI=1S/C20H20N2O3/c1-9(23)14-18(24)17-16-11-8-21-13-6-4-5-10(15(11)13)7-12(16)20(2,3)22(17)19(14)25/h4-6,8,12,16-17,21,24H,7H2,1-3H3/t12-,16+,17+/m1/s1 Key: SZINUGQCTHLQAZ-DQYPLSBCSA-N ; InChI=1/C20H20N2O3/c1-9(23)14-18(24)17-16-11-8-21-13-6-4-5-10(15(11)13)7-12(16)20(2,3)22(17)19(14)25/h4-6,8,12,16-17,21,24H,7H2,1-3H3/t12-,16+,17+/m1/s1 Key: SZINUGQCTHLQAZ-DQYPLSBCBO;
	SMILES CC(=O)C1=C(O)[C@H]5N(C1=O)[C@@](C)(C)[C@@H]4Cc2cccc3[nH]cc(c23)[C@@H]45;
Properties
Chemical formula	C20H20N2O3
Molar mass	336.391 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

Cyclopiazonic acid (α-CPA), a mycotoxin and a fungal neurotoxin, is made by the molds Aspergillus and Penicillium.^[1]^[2]^[3] It is an indole-tetramic acid that serves as a toxin due to its ability to inhibit calcium-dependent ATPases found in the endoplasmic and sarcoplasmic reticulum.^[4] This inhibition disrupts the muscle contraction-relaxation cycle and the calcium gradient that is maintained for proper cellular activity in cells.^[2]

Cyclopiazonic acid is known to contaminate multiple foods because the molds that produce them are able to grow on different agricultural products, including but not limited to grains, corn, peanuts, and cheese.^[2]^[5] Due to this contamination, α-CPA can be harmful to both humans and farm animals that were exposed to contaminated animal feeds. However, α-CPA needs to be introduced in very high concentrations to produce mycotoxicosis in animals. Due to this, α-CPA is not a potent acute toxin.^[2]

Chemically, CPA is related to ergoline alkaloids. CPA was originally isolated from Penicillium cyclopium and subsequently from other fungi including Penicillium griseofulvum, Penicillium camemberti, Penicillium commune, Aspergillus flavus, and Aspergillus versicolor. CPA only appears to be toxic in high concentrations. Ingestion of CPA causes anorexia, dehydration, weight loss, immobility, and signs of spasm when near death. CPA can be found in molds, corns, peanuts, and other fermented products, such as cheese and sausages.^[6] Biologically, CPA is a specific inhibitor of SERCA ATPase in intracellular Ca²⁺ storage sites.^[7] CPA inhibits SERCA ATPase by keeping it in one specific conformation, thus, preventing it from forming another.^[8] CPA also binds to SERCA ATPase at the same site as another inhibitor, thapsigargin (TG). In this way, CPA lowers the ability of SERCA ATPase to bind an ATP molecule.^[9]

^ Holzapfel CW (March 1968). "The isolation and structure of cyclopiazonic acid, a toxic metabolite of Penicillium cyclopium Westling". Tetrahedron. 24 (5): 2101–19. doi:10.1016/0040-4020(68)88113-X. PMID 5636916.
^ ^a ^b ^c ^d Chang PK, Ehrlich KC, Fujii I (December 2009). "Cyclopiazonic acid biosynthesis of Aspergillus flavus and Aspergillus oryzae". Toxins. 1 (2): 74–99. doi:10.3390/toxins1020074. PMC 3202784. PMID 22069533.
^ Cite error: The named reference Liu_2009 was invoked but never defined (see the help page).
^ Seidler NW, Jona I, Vegh M, Martonosi A (October 1989). "Cyclopiazonic acid is a specific inhibitor of the Ca2+-ATPase of sarcoplasmic reticulum". The Journal of Biological Chemistry. 264 (30): 17816–23. doi:10.1016/S0021-9258(19)84646-X. PMID 2530215.
^ Nishie K, Cole RJ, Dorner JW (September 1985). "Toxicity and neuropharmacology of cyclopiazonic acid". Food and Chemical Toxicology. 23 (9): 831–9. doi:10.1016/0278-6915(85)90284-4. PMID 4043883.
^ Bullerman LB (2003). "MYCOTOXINS | Classifications". Encyclopedia of Food Sciences and Nutrition. pp. 4080–4089. doi:10.1016/B0-12-227055-X/00821-X. ISBN 978-0-12-227055-0.
^ Sosa MJ, Córdoba JJ, Díaz C, Rodríguez M, Bermúdez E, Asensio MA, Núñez F (June 2002). "Production of cyclopiazonic acid by Penicillium commune isolated from dry-cured ham on a meat extract-based substrate". Journal of Food Protection. 65 (6): 988–92. doi:10.4315/0362-028X-65.6.988. PMID 12092733.
^ Soler F, Plenge-Tellechea F, Fortea I, Fernandez-Belda F (March 1998). "Cyclopiazonic acid effect on Ca2+-dependent conformational states of the sarcoplasmic reticulum ATPase. Implication for the enzyme turnover". Biochemistry. 37 (12): 4266–74. doi:10.1021/bi971455c. PMID 9521749.
^ Ma H, Zhong L, Inesi G, Fortea I, Soler F, Fernandez-Belda F (November 1999). "Overlapping effects of S3 stalk segment mutations on the affinity of Ca2+-ATPase (SERCA) for thapsigargin and cyclopiazonic acid". Biochemistry. 38 (47): 15522–7. doi:10.1021/bi991523q. PMID 10569935.

[Holzapfel_1968-1] Holzapfel CW (March 1968). "The isolation and structure of cyclopiazonic acid, a toxic metabolite of Penicillium cyclopium Westling". Tetrahedron. 24 (5): 2101–19. doi:10.1016/0040-4020(68)88113-X. PMID 5636916.

[Chang_2009-2] Chang PK, Ehrlich KC, Fujii I (December 2009). "Cyclopiazonic acid biosynthesis of Aspergillus flavus and Aspergillus oryzae". Toxins. 1 (2): 74–99. doi:10.3390/toxins1020074. PMC 3202784. PMID 22069533.

[Liu_2009-3] Cite error: The named reference Liu_2009 was invoked but never defined (see the help page).

[Seidler_1989-4] Seidler NW, Jona I, Vegh M, Martonosi A (October 1989). "Cyclopiazonic acid is a specific inhibitor of the Ca2+-ATPase of sarcoplasmic reticulum". The Journal of Biological Chemistry. 264 (30): 17816–23. doi:10.1016/S0021-9258(19)84646-X. PMID 2530215.

[Nishie_1985-5] Nishie K, Cole RJ, Dorner JW (September 1985). "Toxicity and neuropharmacology of cyclopiazonic acid". Food and Chemical Toxicology. 23 (9): 831–9. doi:10.1016/0278-6915(85)90284-4. PMID 4043883.

[:0-6] Bullerman LB (2003). "MYCOTOXINS | Classifications". Encyclopedia of Food Sciences and Nutrition. pp. 4080–4089. doi:10.1016/B0-12-227055-X/00821-X. ISBN 978-0-12-227055-0.

[Sosa_2002-7] Sosa MJ, Córdoba JJ, Díaz C, Rodríguez M, Bermúdez E, Asensio MA, Núñez F (June 2002). "Production of cyclopiazonic acid by Penicillium commune isolated from dry-cured ham on a meat extract-based substrate". Journal of Food Protection. 65 (6): 988–92. doi:10.4315/0362-028X-65.6.988. PMID 12092733.

[Soler_1998-8] Soler F, Plenge-Tellechea F, Fortea I, Fernandez-Belda F (March 1998). "Cyclopiazonic acid effect on Ca2+-dependent conformational states of the sarcoplasmic reticulum ATPase. Implication for the enzyme turnover". Biochemistry. 37 (12): 4266–74. doi:10.1021/bi971455c. PMID 9521749.

[Ma_1999-9] Ma H, Zhong L, Inesi G, Fortea I, Soler F, Fernandez-Belda F (November 1999). "Overlapping effects of S3 stalk segment mutations on the affinity of Ca2+-ATPase (SERCA) for thapsigargin and cyclopiazonic acid". Biochemistry. 38 (47): 15522–7. doi:10.1021/bi991523q. PMID 10569935.

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