Phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism caused by deficient phenylalanine hydroxylase (PAH) activity. The deficiency results in increased levels of Phe and its metabolites in fluids and tissues of patients. PKU patients present neurological signs and symptoms including hypomyelination and intellectual deficit. This study assessed brain bioenergetics at 1 h after acute Phe administration to induce hyperphenylalaninemia (HPA) in rats. Wistar rats were randomized in two groups: HPA animals received a single subcutaneous administration of Phe (5.2 μmol/g) plus p-Cl-Phe (PAH inhibitor) (0.9 μmol/g); control animals received a single injection of 0.9% NaCl. In cerebral cortex, HPA group showed lower mitochondrial mass, lower glycogen levels, as well as lower activities of complexes I-III and IV, ATP synthase and citrate synthase. Higher levels of free Pi and phospho-AMPK, and higher activities of LDH, α-ketoglutarate dehydrogenase and isocitrate dehydrogenase were also reported in cerebral cortex of HPA animals. In striatum, HPA animals had higher LDH (pyruvate to lactate) and isocitrate dehydrogenase activities, and lower activities of α-ketoglutarate dehydrogenase and complex IV, as well as lower phospho-AMPK immunocontent. In hippocampus, HPA rats had higher mRNA expression for MFN1 and higher activities of α-ketoglutarate dehydrogenase and isocitrate dehydrogenase, but decreased activities of pyruvate dehydrogenase and complexes I and IV. In conclusion, our data demonstrated impaired bioenergetics in cerebral cortex, striatum and hippocampus of HPA rats.

苯丙酮尿症（PKU）是由苯丙氨酸羟化酶（PAH）活性不足引起的苯丙氨酸（Phe）代谢紊乱。缺乏会导致患者体液和组织中Phe及其代谢产物的水平升高。PKU患者表现出神经系统症状和体征，包括髓鞘过少和智力缺陷。这项研究评估了急性Phe给药后1小时诱发大鼠高苯丙氨酸血症（HPA）的大脑生物能。Wistar大鼠随机分为两组：HPA动物皮下注射Phe（5.2μmol/ g）加p-Cl-Phe（PAH抑制剂）（0.9μmol/ g）；对照动物单次注射0.9％NaCl。在大脑皮层中，HPA组的线粒体质量降低，糖原水平降低，复合物I-III和IV的活性降低，ATP合酶和柠檬酸合酶。在HPA动物的大脑皮层中还报告了更高水平的游离Pi和磷酸-AMPK，以及更高的LDH，α-酮戊二酸脱氢酶和异柠檬酸脱氢酶活性。在纹状体中，HPA动物具有较高的LDH（丙酮酸至乳酸盐）和异柠檬酸脱氢酶活性，而α-酮戊二酸脱氢酶和复合物IV的活性较低，并且磷-AMPK免疫含量较低。在海马中，HPA大鼠的MFN1 mRNA表达较高，α-酮戊二酸脱氢酶和异柠檬酸脱氢酶的活性较高，而丙酮酸脱氢酶和复合物I和IV的活性降低。总之，我们的数据表明HPA大鼠大脑皮质，纹状体和海马中的生物能受损。HPA动物的大脑皮层中也有α-酮戊二酸脱氢酶和异柠檬酸脱氢酶的报道。在纹状体中，HPA动物具有较高的LDH（丙酮酸至乳酸盐）和异柠檬酸脱氢酶活性，而α-酮戊二酸脱氢酶和复合物IV的活性较低，并且磷-AMPK免疫含量较低。在海马中，HPA大鼠的MFN1 mRNA表达较高，α-酮戊二酸脱氢酶和异柠檬酸脱氢酶的活性较高，而丙酮酸脱氢酶和复合物I和IV的活性降低。总之，我们的数据表明HPA大鼠大脑皮质，纹状体和海马中的生物能受损。HPA动物的大脑皮层中也有α-酮戊二酸脱氢酶和异柠檬酸脱氢酶的报道。在纹状体中，HPA动物具有较高的LDH（丙酮酸至乳酸盐）和异柠檬酸脱氢酶活性，而α-酮戊二酸脱氢酶和复合物IV的活性较低，并且磷-AMPK免疫含量较低。在海马中，HPA大鼠的MFN1 mRNA表达较高，α-酮戊二酸脱氢酶和异柠檬酸脱氢酶的活性较高，而丙酮酸脱氢酶和复合物I和IV的活性降低。总之，我们的数据表明HPA大鼠大脑皮质，纹状体和海马中的生物能受损。HPA动物具有较高的LDH（丙酮酸至乳酸盐）和异柠檬酸脱氢酶活性，而α-酮戊二酸脱氢酶和复合物IV的活性较低，并且磷-AMPK免疫含量较低。在海马中，HPA大鼠的MFN1 mRNA表达较高，α-酮戊二酸脱氢酶和异柠檬酸脱氢酶的活性较高，而丙酮酸脱氢酶和复合物I和IV的活性降低。总之，我们的数据表明HPA大鼠大脑皮质，纹状体和海马中的生物能受损。HPA动物具有较高的LDH（丙酮酸至乳酸盐）和异柠檬酸脱氢酶活性，而α-酮戊二酸脱氢酶和复合物IV的活性较低，并且磷-AMPK免疫含量较低。在海马中，HPA大鼠的MFN1 mRNA表达较高，α-酮戊二酸脱氢酶和异柠檬酸脱氢酶的活性较高，而丙酮酸脱氢酶和复合物I和IV的活性降低。总之，我们的数据表明HPA大鼠大脑皮质，纹状体和海马中的生物能受损。但丙酮酸脱氢酶和复合物I和IV的活性降低。总之，我们的数据表明HPA大鼠大脑皮质，纹状体和海马中的生物能受损。但丙酮酸脱氢酶和复合物I和IV的活性降低。总之，我们的数据表明HPA大鼠大脑皮质，纹状体和海马中的生物能受损。