Metabolism of acetyl‐l‐carnitine for energy and neurotransmitter synthesis in the immature rat brain
Open Access
- 6 July 2010
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 114 (3), 820-831
- https://doi.org/10.1111/j.1471-4159.2010.06807.x
Abstract
J. Neurochem. (2010) 114, 820–831. Abstract Acetyl‐l‐carnitine (ALCAR) is an endogenous metabolic intermediate that facilitates the influx and efflux of acetyl groups across the mitochondrial inner membrane. Exogenously administered ALCAR has been used as a nutritional supplement and also as an experimental drug with reported neuroprotective properties and effects on brain metabolism. The aim of this study was to determine oxidative metabolism of ALCAR in the immature rat forebrain. Metabolism was studied in 21–22 day‐old rat brain at 15, 60 and 120 min after an intraperitoneal injection of [2‐13C]acetyl‐l‐carnitine. The amount, pattern, and fractional enrichment of 13C‐labeled metabolites were determined by ex vivo13C‐NMR spectroscopy. Metabolism of the acetyl moiety from [2‐13C]ALCAR via the tricarboxylic acid cycle led to incorporation of label into the C4, C3 and C2 positions of glutamate (GLU), glutamine (GLN) and GABA. Labeling patterns indicated that [2‐13C]ALCAR was metabolized by both neurons and glia; however, the percent enrichment was higher in GLN and GABA than in GLU, demonstrating high metabolism in astrocytes and GABAergic neurons. Incorporation of label into the C3 position of alanine, both C3 and C2 positions of lactate, and the C1 and C5 positions of glutamate and glutamine demonstrated that [2‐13C]ALCAR was actively metabolized via the pyruvate recycling pathway. The enrichment of metabolites with 13C from metabolism of ALCAR was highest in alanine C3 (11%) and lactate C3 (10%), with considerable enrichment in GABA C4 (8%), GLN C3 (∼ 4%) and GLN C5 (5%). Overall, our 13C‐NMR studies reveal that the acetyl moiety of ALCAR is metabolized for energy in both astrocytes and neurons and the label incorporated into the neurotransmitters glutamate and GABA. Cycling ratios showed prolonged cycling of carbon from the acetyl moiety of ALCAR in the tricarboxylic acid cycle. Labeling of compounds formed from metabolism of [2‐13C]ALCAR via the pyruvate recycling pathway was higher than values reported for other precursors and may reflect high activity of this pathway in the developing brain. This is, to our knowledge, the first study to determine the extent and pathways of ALCAR metabolism for energy and neurotransmitter biosynthesis in the brain.Keywords
This publication has 73 references indexed in Scilit:
- Delayed cerebral oxidative glucose metabolism after traumatic brain injury in young ratsJournal of Neurochemistry, 2009
- Acetate transport and utilization in the rat brainJournal of Neurochemistry, 2009
- New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscleThe Journal of Physiology, 2007
- Hyperoxic Reperfusion After Global Ischemia Decreases Hippocampal Energy MetabolismStroke, 2007
- Redistribution of Neuroactive Amino Acids in Hippocampus and Striatum during Hypoglycemia: A Quantitative Immunogold StudyJournal of Cerebral Blood Flow & Metabolism, 2001
- In vitro and ex vivo 13C-NMR Spectroscopy Studies of Pyruvate Recycling in BrainDevelopmental Neuroscience, 1998
- High Uptake of [2-11C]Acetyl-l-Carnitine into the Brain: A Pet StudyBiochemical and Biophysical Research Communications, 1997
- Metabolism of [U‐13C5]Glutamine in Cultured Astrocytes Studied by NMR Spectroscopy: First Evidence of Astrocytic Pyruvate RecyclingJournal of Neurochemistry, 1996
- Approaches to Studies on Neuronal/Glial Relationships by 13C-MRS AnalysisDevelopmental Neuroscience, 1996
- Uptake, release and metabolism of alaume in neurons and astrocytes in primary culturesJournal of Neuroscience Research, 1993