Impaired mitochondrial fatty acid oxidation in autism Glutamate-induced mitochondrial dysfunction indirectly and selectively suppresses mitochondrial fatty acid -oxidation.The formation of aspartate from glutamate via the transaminase reaction outcompetes citrate synthase for OAA resulting in a dramatic decrease in citrate and effectively shutting down mitochondrial processing of acetyl-CoA [2].High levels of acetyl-CoA then feedback inhibit mitochondrial -oxidation.Indirectly, the energetic outward transport of aspartate leads to an increased flux through malate dehydrogenase, which causes an increase in the mitochondrial NADH/NAD + ratio, which inhibits -oxidation at the NAD + -linked -hydroxyacyl-CoA dehydrogenase reaction[120].The extra-mitochondrial effects of disrupted mitochondrial fatty acid -oxidation are related to the carnitine-dependency of this system.Carnitine performs two essential metabolic functions.Its primary and most widely recognized function is to shuttle fatty acids (palmitate (16:0) and stearate (18:0)) from the cytosol into the mitochondrial matrix where it can be -oxidized to acetyl-CoA.Its secondary, less recognized function is to shuttle excess acetyl-CoA out of the mitochondrial matrix to the cytosol (for reviews see [121-124])
Alcohol-induced oxidative/nitrosative stress alters brain mitochondrial membrane properties
Antioxidant activity of carvedilol in cardiovascular disease
Parker BA, Sturm K, MacIntosh CG, Feinle C, Horowitz M, Chapman IM: Relation between food intake and visual analogue scale ratings of appetite and other sensations in healthy older and young subjects
Niacin requirements for genomic stability
Acetylation of human mitochondrial citrate carrier modulates mitochondrial citrate/malate exchange activity to sustain NADPH production during macrophage activation
