Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Ramiro Barcelos 2600, Porto Alegre, RS, CEP 90035-003, Brazil.
Centro Universitário Metodista IPA, Rua Cel. Joaquim Pedro Salgado, 80, Porto Alegre, RS, CEP 90420-060, Brazil.
Mol Neurobiol. 2018 Jun;55(6):5101-5110. doi: 10.1007/s12035-017-0711-3. Epub 2017 Aug 24.
β-Alanine occurs naturally in the human central nervous system and performs different functions. It can act as either a neurotransmitter or a neuromodulator, depletion of taurine levels and competitive antagonist of γ-aminobutyric acid (GABA). The β-amino acid accumulation exerts an important biological function as delay in brain development, oxidative stress and disturbances in energy metabolism, characterized as an inborn error of metabolism classified as β-alaninemia. We evaluated the effects of the chronic administration of β-alanine on some parameters of oxidative stress and enzymes of energy metabolism in cerebral cortex and cerebellum of 21-day-old Wistar rats. The animals received peritoneal injections of β-alanine (300 mg/kg of body weight), and the controls received the same volume (10 μl/g of body weight) of saline solution (NaCl 0.9%), twice a day at 12-h interval, from the 7th to the 21st postpartum day. We observed that β-amino acid was able to increase the levels of reactive oxygen species (ROS) in the two tissues; however, only in cerebral cortex total content of sulfhydryl was increased. ROS are possibly acting on antioxidant enzymes glutathione peroxidase (GPx) (cerebral cortex and cerebellum) and superoxide dismutase (SOD) (cerebellum) inhibiting their activities. We also evaluated the activities of enzymes of the phosphoryl transfer network, where we observed an increase in hexokinase and cytosolic creatine kinase (Cy-CK) activities; however, it decreased glyceraldehyde 3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK) and lactate dehydrogenase (LDH) activities, in both tissues. Besides, the β-alanine administration increased the activities of complex II, complex IV and succinate dehydrogenase (SDH). Those results suggest that the chronic administration of β-alanine causes cellular oxidative damage, significantly changing the energy metabolism.
β-丙氨酸自然存在于人体中枢神经系统中，具有不同的功能。它可以作为神经递质或神经调质，耗尽牛磺酸水平并成为γ-氨基丁酸（GABA）的竞争性拮抗剂。β-氨基酸的积累具有重要的生物学功能，可导致大脑发育迟缓、氧化应激和能量代谢紊乱，表现为代谢缺陷，归类为β-丙氨酸血症。我们评估了慢性给予β-丙氨酸对 21 日龄 Wistar 大鼠大脑皮层和小脑某些氧化应激参数和能量代谢酶的影响。动物接受腹膜内注射β-丙氨酸（300mg/kg 体重），对照组接受相同体积（10μl/g 体重）的生理盐水（0.9%NaCl），每天两次，间隔 12 小时，从产后第 7 天到第 21 天。我们观察到β-氨基酸能够增加两种组织中的活性氧（ROS）水平；然而，只有大脑皮层的总巯基含量增加。ROS 可能作用于抗氧化酶谷胱甘肽过氧化物酶（GPx）（大脑皮层和小脑）和超氧化物歧化酶（SOD）（小脑），抑制其活性。我们还评估了磷酸转移网络中酶的活性，其中我们观察到己糖激酶和细胞质肌酸激酶（Cy-CK）的活性增加；然而，它降低了甘油醛 3-磷酸脱氢酶（GAPDH）、丙酮酸激酶（PK）和乳酸脱氢酶（LDH）的活性，在两种组织中均如此。此外，β-丙氨酸的给予增加了复合物 II、复合物 IV 和琥珀酸脱氢酶（SDH）的活性。这些结果表明，慢性给予β-丙氨酸会导致细胞氧化损伤，显著改变能量代谢。
