ALCARvsNAC

ALCAR crosses the blood-brain barrier via the organic cation transporter (OCTN2) more effectively than L-carnitine. In neurons, it is hydrolyzed by carnitine acetyltransferase to donate its acetyl group to coenzyme A, forming acetyl-CoA—which can then be used for acetylcholine synthesis via choline acetyltransferase, effectively providing raw material for the memory neurotransmitter. ALCAR also transports long-chain fatty acids across the inner mitochondrial membrane via the carnitine palmitoyltransferase system for beta-oxidation and ATP production. ALCAR activates nerve growth factor (NGF) signaling, possibly through modulation of NGF receptor (TrkA) expression or downstream MAPK/ERK pathways. It has antioxidant properties, reducing lipid peroxidation in mitochondrial membranes and scavenging free radicals. These mechanisms support cognitive function and neuroprotection.

NAC is deacetylated to cysteine, the rate-limiting substrate for glutathione synthesis via gamma-glutamylcysteine synthetase and glutathione synthetase. Glutathione (GSH) is the primary intracellular antioxidant in neurons, neutralizing reactive oxygen species and maintaining redox balance. NAC also activates the cystine-glutamate antiporter (System Xc-, composed of SLC7A11 and SLC3A2 subunits), which exchanges extracellular cystine for intracellular glutamate in a 1:1 ratio. This non-vesicular mechanism modulates extrasynaptic glutamate levels, reducing NMDA receptor overactivation and excitotoxicity. The glutamate-modulating effect explains NAC's promise in OCD (reducing corticostriatal glutamate hyperactivity), addiction (normalizing nucleus accumbens glutamate after drug exposure), and neurodegenerative conditions involving glutamate dysregulation.