Creatine and Taurine as Novel Competitive Inhibitors of Acetylcholinesterase: A Biochemical Basis for Nutritional Modulation of Brain Function

Acetylcholinesterase (AChE) is a key enzyme responsible for terminating cholinergic neurotransmission by hydrolyzing acetylcholine. While clinically approved AChE inhibitors such as donepezil, rivastigmine, and galantamine are used in the symptomatic treatment of Alzheimer's disease and related dementias, little is known about the modulatory effects of common dietary compounds on AChE activity. In this study, we investigated the influence of creatine (CR) and taurine (TA)-two widely consumed nutritional supplements with reported neuroprotective and cognitive-enhancing properties-on AChE. Enzyme kinetics were evaluated using a modified Ellman's method, and Lineweaver-Burk analyses revealed that both CR and TA act as competitive inhibitors. Calculated parameters (Km, Vmax), inhibition constants (Ki), and half maximal inhibitory concentrations (IC₅₀) consistently indicated stronger potency for CR (IC₅₀ = 0.0056 ± 0.00018 mM) compared to TA (IC50 = 0.0097 ± 0.00035 mM). To complement the experimental data, molecular docking was performed using two crystal structures of human AChE. Docking confirmed that both ligands preferentially occupy the active-site region in a manner consistent with competitive inhibition, with CR showing more favorable binding scores than TA. Although markedly weaker than clinical drugs, these findings provide the first biochemical and in silico evidence that CR and TA directly interact with AChE, suggesting subtle cholinergic modulation relevant to cognitive function and neuroprotection.