Ramsey, Una Patricia.2014-10-2119941994AAINN98928http://hdl.handle.net/10222/55458Domoic acid and kainic acid are neurotoxic amino acids that belong to a group of compounds called the kainoids. The pathway of domoic acid biosynthesis was investigated in the photosynthetic single-celled plankton or diatom Pseudonitzschia pungens f. multiseries using both $\sp $C- and $\sp $C-labelled precursors. Labelling with (1,2-$\sp $C) -acetate revealed that domoic acid is biosynthesized by the condensation of an isoprenoid chain with a citric acid cycle product. The addition of (1,2-$\sp $C) -acetate early and late during exponential growth did not affect the resulting $\sp $C enrichment pattern. Further studies with (2-$\sp $C, $\rm\sp2H\sb3$) -acetate showed that the hydroxyl group of isocitrate is converted to a carbonyl group before the transamination reaction, suggesting that the citric acid cycle product is a derivative of glutamate. (1,5-$\sp $C) -Citrate, (1-$\sp $C) -$\alpha$-ketoglutarate and L (1-$\sp $C) -glutamate were incorporated into domoic acid at low levels.The Palmaria palmata mutant GM, a known producer of kainic acid, was examined for possible intermediates of kainic acid biosynthesis. An unknown secondary amino acid was isolated and identified as 1$\sp\prime$-hydroxydihydrokainic acid. This compound is probably formed by hydration of kainic acid and is unlikely to be a precursor of kainic acid. 1$\sp\prime$-Hydroxydihydrokainic acid is able to chelate both calcium and copper and may function as a metal detoxifier within the cells.Two protein prenylation inhibitors, gliotoxin and (+)-limonene did not inhibit domoic acid biosynthesis in P. pungens f. multiseries. (+)-Limonene at a final concentration of 0.5 $\mu$M did result in an increase in domoic acid production. Preliminary kainic acid prenyltransferase assays with (1,5-$\sp $C) -citrate, (1-$\sp $C) -$\alpha$-ketoglutarate or L (1-$\sp $c) -glutamate added did not produce $\sp $C-labelled kainic acid.Thesis (Ph.D.)--Dalhousie University (Canada), 1994.Chemistry, Biochemistry.text