Okadaic acid

Structural formula
General
Surname	Okadaic acid
other names	OA 9,10-deepithio-9,10-didehydroacanthifolicin
Molecular formula	C 44 H 68 O 13
Brief description	white solid
External identifiers / databases
CAS number 78111-17-8 EC number 616-589-8 ECHA InfoCard 100.116.145 PubChem 446512 ChemSpider 393845 DrugBank DB02169 Wikidata Q414042
properties
Molar mass	805.00 g · mol -1
Physical state	firmly
Melting point	144-146 ° C
solubility	almost insoluble in water
safety instructions
GHS labeling of hazardous substances danger H and P phrases H: 301-311-315-331 P: 261-280-301 + 310-311
Toxicological data	192 µg kg −1 ( LD 50 ,  mouse ,  ip )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Okadaic acid is a toxin produced by some marine algae ( dinoflagellates ). It accumulates in clams and causes fish poisoning .

Occurrence

Okadaic acid was named after the marine sponge Halichondria okadai , which occurs on the Japanese Pacific coast and from which okadaic acid was isolated for the first time. It was also isolated as a cytotoxin from the H. malanodocia sponge found in the Caribbean . Originally okadaic acid is produced by marine algae belonging to the dinophytes ( dinoflagellates ) , such as Dinophysis sp. or Prorocentrum sp. that produce okadaic acid in a precursor that is harmless to them, the so-called dinophysistoxin-4 . The dinophysistoxin-4 is released from the dinophytes to the surrounding medium or escapes upon death and is hydrolyzed in the medium to give okadaic acid diol ester.

properties

Okadaic acid diolester is fat-soluble, so it can pass through biomembranes and penetrate into cells of other organisms , where the okadaic acid diolester is hydrolyzed again to the actual, toxic okadaic acid.

toxicology

The toxicity of okadaic acid based on the inhibition of the serine - / threonine -specific protein - phosphatases 2b (PP2B), whereupon the classification of okadaic acid as type 1 (PP1), 2a (PP2A) and hepatotoxin and as a tumor promoter is based. The inhibitory effect on the individual phosphatase types is dependent on the concentration. Type 2a phosphatase , which is already 50% inhibited at okadaic acid concentrations in the range of 1 nM ( IC ₅₀ ), is most strongly inhibited . The IC ₅₀ for PP1 is 0.3 - 1 μM and for PP2B is over 1 μM. So induces Okada acid, for example, a permanent. Muscle contraction , as the dephosphorylation of the contraction of the involved protein myosin by the serine - / threonine -specific protein - phosphatases can no longer take place.

The lethal concentration of okadaic acid in mice ( LD ₅₀ ) is 192 μg / kg, ip. ( intraperitoneal )

Individual evidence

1. ↑ ^{a b c d} data sheet Okadaic acid from Prorocentrum concavum at Sigma-Aldrich , accessed on April 16, 2011 ( PDF ).
2. ↑ ^{a b} Data sheet okadaic acid from Acros, accessed on February 20, 2010.
3. ↑ Kazuo Tachibana, Paul J. Scheuer, Yasumasa Tsukitani, Hiroyuki Kikuchi, Donna Van Engen, Jon Clardy, Yalamanchili Gopichand, Francis J. Schmitz: Okadaic acid, a cytotoxic polyether from two marine sponges of the genus Halichondria. In: Journal of the American Chemical Society . 103, 9, 1981, pp. 2469-2471. doi: 10.1021 / ja00399a082 .
4. ^ Robert Edward Lee: Phycology. 4th edition. Cambridge University Press, New York 2008, ISBN 978-0-521-68277-0 .
5. ↑ ^{a b c} H. Ishihara, BL Martin, DL Brautigan, H. Karaki, H. Ozaki, Y. Kato, N. Fusetani, S. Watabe, K. Hashimoto, D. Uemura et al: Calyculin A and okadaic acid: inhibitors of protein phosphatase activity. In: Biochemical and Biophysical Research Communications . 159, 3, March 31, 1989, pp. 871-877.
6. ↑ H. Ibelgaufts: okadaic acid. ( Memento of February 10, 2013 in the web archive archive.today ) Retrieved on July 7, 2010.

literature

• Robert Edward Lee: Phycology 4th Edition. Cambridge University Press, New York 2008, ISBN 978-0-521-68277-0 .
• CJ Forsyth, RA Urbanek: An Efficient Total Synthesis of Okadaic Acid. In: Journal of the American Chemical Society. 119, 35, 1997, pp. 8381-8382, doi: 10.1021 / ja9715206 .