Acetylcholinesterase Activity and Biogenic Amines in Phenylketonuria

Abstract

Phenylketonuria (PKU) is a disorder in which the aromatic amino acid Phe cannot be converted to Tyr (1)(2). Unfortunately, many PKU patients do not adhere to their low-Phe diet (off diet), which leads to high concentrations of the amino acid in their blood (1)(2). High Phe concentrations interfere with the production of adrenaline (A), noradrenaline (NA), and dopamine (DA) (1)(3). Furthermore, Krause et al. (4) reported an inverse relationship between NA and DA plasma concentrations and Phe because high Phe concentrations decrease the availability of the amino acids Tyr and Trp, the precursors of catecholamines and serotonin [5-hydroxytryptamine (5HT)], respectively (5)(6)(7). Acetylcholinesterase (AChE) is a membrane-bound enzyme with its active side exposed at the external leaflet of the bilayer (ectoenzyme). When the enzyme is inhibited, it can no longer participate in the hydrolysis of acetylcholine (ACh) (8), involving parasympathetic, sympathetic, peripheral, and central nervous system function (8)(9)(10). Alterations of the above substances in the cerebrospinal fluid are correlated with AChE activity in the cerebrospinal fluid of patients with mental impairment (11). In our previous study (12), incubation of high Phe concentrations with human AChE type XIII led to inhibition of the enzyme (40–60%). The effect of Phe on AChE of rat diaphragm and rat brain showed a concentration-dependent enzyme inhibition (13)(14). We therefore aimed to evaluate AChE activities in the erythrocyte membranes from patients with PKU and to correlate the enzyme activities with blood concentrations of the biogenic amines A, NA, DA, and 5HT as well as with the precursors Tyr and …