Enhanced Production of Fatty Acids via Redirection of Carbon Flux in Marine Microalga Tetraselmis sp.

Lipids in microalgae are energy-rich compounds and considered as an attractive feedstock for biodiesel production. To redirect carbon flux from competing pathways to the fatty acid synthesis pathway of Tetraselmis sp., we used three types of chemical inhibitors that can block the starch synthesis pathway or photorespiration, under nitrogen-sufficient and nitrogen-deficient conditions. The starch synthesis pathway in chloroplasts and the cytosol can be inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea and 1,2-cyclohexane diamine tetraacetic acid (CDTA), respectively. Degradation of glycine into ammonia during photorespiration was blocked by aminooxyacetate (AOA) to maintain biomass concentration. Inhibition of starch synthesis pathways in the cytosol by CDTA increased fatty acid productivity by 27% under nitrogen deficiency, whereas the blocking of photorespiration in mitochondria by AOA was increased by 35% under nitrogen-sufficient conditions. The results of this study indicate that blocking starch or photorespiration pathways may redirect the carbon flux to fatty acid synthesis.

Influence of bilateral clamping of carotid arteries on the seizures susceptibility and central action of AOAA in mice.

In the experiments carried out on Albino-Swiss mice it was found, that bilateral clamping of carotid arteries (BCCA) for 30 min produce the increase of GABA content in hippocampus, striatum and frontal cortex and decrease of the seizures susceptibility to bicuculline, investigated 7 days after surgery. Moreover, BCCA modulates the action of aminooxyacetic acid (AOAA): potentiates anticonvulsive effect of low doses of AOAA (33 mg/kg) and inhibits the convulsive action of high doses. Also the potentiation of the anticonvulsive effect of diazepam, phenobarbital and valproic acid (VPA) was observed in BCCA and AOAA (CD97, 150 mg/kg) treated animals. Observed effects suggests that enhanced GABA-ergic activity and decrease of excitatory amino acid (EAA) system could be involved in these processes.

Aminooxyacetic acid striatal lesions attenuated by 1,3-butanediol and coenzyme Q10.

We previously showed that intrastriatal administration of aminooxyacetic acid (AOAA) produces striatal lesions by a secondary excitotoxic mechanism associated with impairment of oxidative phosphorylation. In the present study, we show that and the specific complex I inhibitor rotenone produces a similar neurochemical profile in the striatum, consistent with an effect of AOAA on energy metabolism. Lesions produced by AOAA were dose-dependently blocked by MK-801, with complete protection against GABA and substance P depletions at a dose of 3 mg/kg. AOAA lesions were significantly attenuated by pretreatment with either 1,3-butanediol or coenzyme Q10, two compounds which are thought to improve energy metabolism. These results provide further evidence that AOAA produces striatal excitotoxic lesions as a consequence of energy depletion and they suggest therapeutic strategies which may be useful in neurodegenerative diseases.

Aminooxyacetic acid produces excitotoxic brain injury in neonatal rats.

Impairment of cellular energy metabolism plays an important role in the expression of brain injury resulting from a variety of acute neurologic disorders. The role of mitochondrial energy metabolism in excitotoxic perinatal brain injury was assessed by studying the toxicity of aminooxyacetic acid (AOAA), an inhibitor of mitochondrial malate-aspartate shunt, in postnatal (PND) 7 rats. Intrastriatal injection of AOAA produced seizures and dose-dependent excitotoxic injury. The neuronal damage was attenuated by pyridoxine suggesting involvement of pyridoxal dependent mechanisms. The lesion was selectively blocked by the NMDA antagonist MK-801 but not the AMPA antagonist GYKI-52466. Furthermore, AOAA potentiated NMDA, but not AMPA or 1S,3R-ACPD, induced brain injury. The data suggest that regional impairment of cellular energy metabolism is an important determinant of selective vulnerability to excitotoxic injury in perinatal rats. Furthermore, the role of impaired energy metabolism is particularly relevant to NMDA receptor mediated brain injury.

[The role of cholinergic processes in realizing the analgesic effect of GABA-positive preparations]. / O roli kholinergicheskikh protsessov v realizatsii boleutoliaiushchego éffekta GAMK-pozitivnykh preparatov.

In experiments on male rats it was shown that scopolamine diminished while pilocarpine and physostigmine potentiated the antinociceptive effect of baclofen, gamma-acetylenic-GABA, THIP and depakine. At the same time the antinociceptive effect of pilocarpine virtually underwent no changes in baclofen- and depakine-tolerant animals. The results suggest that the cholinergic processes may be involved in GABAergic antinociception but not in the development of tolerance to the antinociceptive effect of GABA-positive drugs.

[Antagonistic effect of sodium hydroxybutyrate on several effects of aminoxyacetic acid]. / Antagonisticheskoe vliianie oksibutirata natriia na nekotorye éffekty aminooksiuksusnoi kisloty

A well-known protective effect of aminooxyacetic acid against thiosemicarbazide convulsions was confirmed; it was shown that a similar, although somewhat weaker activity, was exerted by sodium hydroxybutyrate. Surprisingly, the effect of aminooxyacetic acid was diminished by sodium hydroxybutyrate. Sodium hydroxybutyrate in combination with aminooxyacetic acid decreased the protective activity of the latter against thiosemicarbazide convulsions and diminished the extent of GABA accumulation characteristic of aminooxyacetic acid action. This effect is attributed to the competition between the aminooxyacetic acid, sodium hydroxybutyrate and GABA for alpha-ketoglutarate-GABA-transaminase and possible for the GABA-ergic receptor.