Effects of β-alanine administration on selected parameters of oxidative stress and phosphoryltransfer network in cerebral cortex and cerebellum of rats

Abstract

β-Alanine is a β-amino acid derivative of the degradation of pyrimidine uracil and precursor of the oxidative substrate acetyl-coenzyme A (acetyl-CoA). The accumulation of β-alanine occurs in β-alaninemia, an inborn error of metabolism. Patients with β-alaninemia may develop neurological abnormalities whose mechanisms are far from being understood. In this study we evaluated the effects of β-alanine administration on some parameters of oxidative stress and on creatine kinase, pyruvate kinase, and adenylate kinase in cerebral cortex and cerebellum of 21-day-old rats. The animals received three peritoneal injections of β-alanine (0.3 mg /g of body weight) and the controls received the same volume (10 μL/g of body weight) of saline solution (NaCl 0.85 %) at 3 h intervals. CSF levels of β-alanine increased five times, achieving 80 μM in the rats receiving the amino acid. The results of β-alanine administration in the parameters of oxidative stress were similar in both tissues studied: reduction of superoxide dismutase activity, increased oxidation of 2',7'-dihydrodichlorofluorescein, total content of sulfhydryl and catalase activity. However, the results of the phosphoryltransfer network enzymes were similar in all enzymes, but different in the tissues studied: the β-alanine administration was able to inhibit the enzyme pyruvate kinase, cytosolic creatine kinase, and adenylate kinase activities in cerebral cortex, and increase in cerebellum. In case this also occurs in the patients, these results suggest that oxidative stress and alteration of the phosphoryltransfer network may be involved in the pathophysiology of β-alaninemia. Moreover, the ingestion of β-alanine to improve muscular performance deserves more attention in respect to possible side-effects.

Mitochondrial defects associated with β-alanine toxicity: relevance to hyper-beta-alaninemia

“…Gemelli et al [9] proposed that oxidative stress might contribute to the symptoms of hyper-beta-alaninemia. A major source of superoxide production in the cytosol of most cells is NADPH oxidase.…”

“…Gemelli et al [9] have suggested that the neurotoxicity might be caused by oxidative stress. In β-alanine-treated rats, they observed an increase in catalase activity of the cerebral cortex and cerebellum and a reduction in the activity of superoxide dismutase, which together are capable of elevating H 2 O 2 and superoxide anion.…”

Perinatal hypoxia: different effects of the inhibitors of GABA transporters GAT1 and GAT3 on the initial velocity of [3H]GABA uptake by cortical, hippocampal, and thalamic nerve terminals

“…Moreover, Mathers et al (34) has recently shown that chemical transmission at the inhibitory synapses in the thalamus involves receptor activation by β-alanine. The importance of β-alanine for synaptic transmission is supported by the fact that the patients with β-alaninemia (accumulation of β-alanine as inborn error of metabolism) may develop neurological abnormalities whose mechanisms are far from being understood (35). …”

Evaluation of Oxidative Stress Parameters and Energy Metabolism in Cerebral Cortex of Rats Subjected to Sarcosine Administration

“…Adenylate kinase (AK) (EC 2.7.4.3) catalyzes the reversible phosphoryl transfer between ATP and AMP [11,12]. This enzyme, along with creatine kinase (CK) (EC 2.7.3.2), hexokinase (HK) (EC 2.7.1.1), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12), is responsible for the enzymatic phosphoryl transfer network or, in other words, responsible for the transfer of the phosphoryl of ATP where it is produced (mainly in the mitochondrial) to the place where it is consumed (mainly in the cytosol) [12].…”