In vitro evidence that phytanic acid compromises Na(+),K(+)-ATPase activity and the electron flow through the respiratory chain in brain cortex from young rats.

Abstract

Phytanic acid (Phyt) tissue concentrations are increased in Refsum disease and other peroxisomal disorders characterized by neurologic damage and brain abnormalities. The present work investigated the in vitro effects of Phyt, at concentrations found in these peroxisomal disorders, on important parameters of energy metabolism in brain cortex of young rats. The parameters analyzed were CO(2) production from labeled acetate and glucose, the activities of the citric acid cycle enzymes citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase and malate dehydrogenase, as well as of the respiratory chain complexes I-IV, creatine kinase and Na(+),K(+)-ATPase. Our results show that Phyt did not alter citric acid cycle enzyme activities, or CO(2) production from acetate, reflecting no impairment of the functionality of the citric acid cycle. In contrast, respiratory chain activities were reduced at complexes I, II, I-III, II-III and IV. Membrane synaptical Na(+),K(+)-ATPase activity was also reduced by Phyt, with no alteration of creatine kinase activity. Considering the importance of the electron flow through the respiratory chain for brain energy metabolism (oxidative phosphorylation) and of Na(+),K(+)-ATPase activity for maintaining membrane potential necessary for neurotransmission, the data indicate that Phyt impairs brain bioenergetics at the level of energy formation, as well as neurotransmission. It is presumed that Phyt-induced impairment of these important systems may be involved at least in part in the neurological damage found in patients affected by disorders in which brain Phyt concentrations are increased.

• Authors: Estela Natacha Brandt Busanello, Carolina Maso Viegas, Alana Pimentel Moura, Anelise Miotti Tonin, Mateus Grings, Carmen R Vargas, Moacir Wajner
• Journal: Brain research (Brain Res) Vol. 1352 Pg. 231-8 (Sep 17 2010) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 20624373 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetates
• Phytanic Acid
• Sodium-Potassium-Exchanging ATPase

Topics

• Acetates (metabolism)
• Animals
• Cell Membrane (enzymology)
• Cerebral Cortex (drug effects, enzymology, metabolism)
• Citric Acid Cycle (drug effects)
• Electron Transport (drug effects)
• Glycolysis (drug effects)
• Oxygen Consumption (drug effects)
• Phytanic Acid (pharmacology)
• Rats
• Refsum Disease (drug therapy, metabolism)
• Sodium-Potassium-Exchanging ATPase (drug effects, metabolism)