Alanine reverses the inhibitory effect of phenylalanine on acetylcholinesterase activity

The aim of this work was to evaluate, in vitro, the effect of L-alanine (Ala) on suckling rat brain acetylcholinesterase (AChE) and on eel Electrophorus electricus pure AChE inhibited by L-phenylalanine (Phe) as well as to investigate whether Phe or Ala is a competitive inhibitor or an effector of the enzyme. AChE activity was determined in brain homogenates and in the pure enzyme after 1 h preincubation with 1.2 mM of Phe or Ala as well as with Phe plus Ala. The activity of the pure AChE was also determined using as a substrate different amounts of acetylthiocholine. Ala reversed completely the inhibited AChE by Phe (18-20% in 500-600 μM substrate, p<0.01). Lineweaver-Burk plots showed that Vmax remained unchanged. However, KM was found increased with Phe (150%, p<0.001), decreased with Ala alone (50%, p<0.001) and unaltered with Phe plus Ala. It is suggested that: a) Phe presents a competitive inhibitory action with the substrate whereas Ala a competitive activation; b) Ala competition with Phe might unbind the latter from AChE molecule inducing the enzyme stimulation; c) Ala might reverse the inhibitory effect of Phe on brain AChE in phenylketonuric patients, if these results are extended into the in vivo reality

The effect of galactose metabolic disorders on rat brain acetylcholinesterase activity

To evaluate whether in classical galactosemia galactose (Gal), galactose-1-phosphate (Gal-1-P) and galactitol (Galtol) affect brain acetylcholinesterase (AChE) activity, various concentrations (1-16mM) of these compounds were preincubated with brain homogenates of suckling rats as well as with pure eel Electroforus electricus AChE at 37°C for 1 h. Initially, Galtol (up to 2.0mM) increased (25%) AChE activity which decreased, thereafter, reaching the control value in high Galtol concentrations. Gal-1-P decreased gradually the enzyme activity reaching a plateau (38%), when incubated with 8-16 mM. However, when the usually found 2 mM of Galtol and 2 mM of Gal-1-P, concentrations in galactosemia were added in the incubation mixture simultaneously, brain AChE was stimulated (16%). Galtol or Gal-1-P modulated brain AChE as well as enzyme activity of E. electricus in the same way. Gal, Glucose (Glu) and glucose-1-phosphate (Glu-1-P) had no effect on AChE activity. It is suggested that Galtol as well as Gal-1-P can affect acetylcholine degradation acting directly on AChE molecule. Consequently the direct action of these substances on the enzyme might explain the brain cholinergic dysfunction in untreated galactosemia patients

The Effect of Galactose Metabolic Disorders on Rat Brain Na+,K+-ATPase Activity

To evaluate the effect of galactose metabolic disorders on the brain Na+,K+-ATPase in suckling rats. Separate preincubations of various concentrations (1-16 mM) of the compounds galactose-1-phosphate (Gal-1-P) and galactitol (galtol) with whole brain homogenates at 37 °C for 1 h resulted in a dose dependent inhibition of the enzyme whereas the pure enzyme (from porcine cerebral cortex) was stimulated. Glucose-1-phosphate (Glu-1-P) or galactose (Gal) stimulated both rat brain Na+,K+-ATPase and pure enzyme. A mixture of Gal-1-P (2 mM), galtol (2 mM) and Gal (4 mM), concentrations commonly found in untreated patients with classical galactosemia, caused a 35% (p < 0.001) rat brain enzyme inhibition. Additionally, incubation of a mixture of galtol (2 mM) and Gal (1 mM), which is usually observed in galactokinase deficient patients, resulted in a 25% (p < 0.001) brain enzyme inactivation. It is suggested that: a) The indirect inhibition of the brain Na+,K+-ATPase by Gal-1-P should be due to the presence of the epimer Gal and phosphate and that the pure enzyme direct activation by Gal-1-P and Glu-1-P to the presence of phosphate only. b) The observed brain Na+,K+-ATPase inhibitions in the presence of toxic concentrations of Gal-1-P and/ or galtol could modulate the neural excitability, the metabolic energy production and the catecholaminergic and serotoninergic system. © 2002, Verlag der Zeitschrift für Naturforschung. All rights reserved

The protective effect of L-cysteine and glutathione on the adult and aged rat brain (Na+,K+)-ATPase and Mg2+-ATPase activities in galactosemia in vitro

The aim of this study was to evaluate whether the addition of the antioxidants L-cysteine (Cys) or the reduced glutathione (GSH) could reverse the alterations of brain total antioxidant status (TAS) and the modulated activities of the enzymes (Na+,K+)-ATPase, and Mg 2+-ATPase in adult or aged rat brain homogenates induced by galactosemia in vitro. Mixture A [mix. A: galactose-1-phosphate (Gal-1-P, 2 mM) plus galactitol (Galtol, 2 mM) plus galactose (Gal, 4 mM) = classical galactosemia] or mixture B [mix. B: Galtol (2 mM) plus Gal (1 mM) = galactokinase deficiency galactosemia] were preincubated in the presence or absence of Cys (0.83 mM) or GSH (0.83 mM) with adult or aged brain homogenates at 37°C for 1 h. TAS and the enzyme activities were determined spectrophotometrically. Mix. A or mix. B preincubation with the adult brain resulted in a significant (Na+,K+)-ATPase inhibition (-30%) and a Mg2+-ATPase stimulation (+300% and +33%, respectively), whereas lower modifications of the enzyme activities (p < 0.001) were found in the aged brain. Gal mixtures decreased TAS by 40% (p < 0.001) and by 20% (p < 0.01) in adult and aged samples, respectively. The antioxidants significantly increased TAS resulting in the reversion of (Na+,K +)-ATPase inhibition and Mg2+-ATPase stimulation by mix. B only. The inhibitory effect of Gal and its derivatives on brain (Na +,K+)-ATPase and their stimulatory effect on Mg 2+-ATPase are being decreased with age, probably due to the producion of free radicals. Cys and GSH increased TAS resulting in a reversion of the inhibited (Na+,K+)-ATPase in both models of the in vitro galactosemia and the stimulated Mg2+-ATPase in galactokinase deficiency galactosemia only. © 2005 Springer Science+Business Media, Inc

L-Phenylalanine Effect on Rat Diaphragm Acetylcholinesterase and Na+,K+-ATPase

I-Phenylalanine, Rat Diaphragm. Acetylcholinesterase, Na+.K+-ATPase The effect of different L-phenylalanine (Phe) concentrations (0.24-12.1 mM), on acetylcholinesterase (AChE) and Na+,K+-ATPase activities of diaphragm homogenates from 21-day old rats and pure enzymes, was investigated at 37 °C. AChE and Na+,K+-ATPase activities were determined after preincubation with Phe. AChE activity in diaphragm homogenate or in pure eel E. electricus enzyme showed a decrease, which reached a maximum of 18% with Phe concentrations of 0.9-12.1 mM. However lower Phe concentrations (0.24 min) increased the enzyme activity (by approximately 22%), only in the diaphragm homogenate. Diaphragm-associated Na+,K+-ATPase activity showed a progressive and concentration-dependent decrease, by about 30-35% in the presence of high Phe concentrations. Pure enzyme activity (from porcine cerebral cortex) was not affected by high Phe concentrations (≥0.48 mM), while it was increased by low concentrations. The above results suggest: a) A direct inactivating effect of high Phe concentrations on AChE and an indirect activating effect induced by low concentrations, b) A direct activating effect of low Phe concentrations and an indirect inactivating effect of high ones on Na+,K+-ATPase. c) The combination of high Phe concentrations effects on AChE and Na+,K+-ATPase could influence the levels of the diaphragm synaptic ACh. © 1998, Verlag der Zeitschrift für Naturforschung. All rights reserved

Classical galactosemia patients can achieve high IQ scores

Very recently, it was reported that a patient with classical galactosemia and a very high intelligence quotient (IQ) score obtained a university degree. In the present study, two siblings with classical galactosemia (homozygous for Q188R mutation) received upper normal IQ scores when tested with psychometric tools. Additionally, the same IQ scores were determined in their healthy brother when tested at the same age. It was concluded that patients could achieve upper normal IQ scores when on diet and followed up closely. Family and especially maternal care may ameliorate the psychomotor development. © 2019 Walter de Gruyter GmbH, Berlin/Boston 2019

Increased blood concentrations of neurotransmission amino acids and modulation of specific enzyme activities after resistance and endurance exercise

Background: There are twenty-one amino acids in the human body and some of them have neurotransmission action during exercise. Aims: The aim of this review is to present the increase of neurotransmission amino acids in the blood after training. Additionally, we highlight the neurotransmission action of certain amino acids and their beneficial effects on a wide range of neurological disorders. Methods: A Medline and Scopus search was performed to identify articles published on this topic. Only articles published in English were considered. Results: Cognitive functioning of memory, attention, arousal, as well as motor control and emotion functioning, are related to modifications in the glutamatergic, monoaminergic and serotonergic systems in patients with some types of dementia. A direct effect of phenylalanine on certain neurotransmission enzymes is also described. Tyrosine is highly involved in dopamine production, resulting in amelioration of the symptoms of patients with moderate Parkinson’s disease via dopamine increase. Conclusions: Training could be beneficial, not only to healthy people but also to patients with moderate neurodegenerative disorders. © 2020, Springer-Verlag Italia S.r.l., part of Springer Nature