Influence of proline on rat brain activities of alanine aminotransferase, aspartate aminotransferase and acid phosphatase

Abstract

Hyperprolinemia type II ( HPII) is an autosomal recessive disorder caused by the severe deficiency of enzyme Delta(1)-pyrroline-5-carboxylic acid dehydrogenase leading to tissue accumulation of proline. Chronic administration of Pro led to significant reduction of cytosolic ALT activity of olfactory lobes (50.57 percent), cerebrum (40 percent) and medulla oblongata (13.71 percent) only. Whereas mitochondrial ALT activity was reduced significantly in, all brain regions such as olfactory lobes (73.23 percent), cerebrum (70.26 percent), cerebellum (65.39 percent) and medulla oblongata (65.18 percent). The effect of chronic Pro administration on cytosolic AST activity was also determined. The cytosolic AST activity from olfactory lobes, cerebrum and medulla oblongata reduced by 75.71, 67.53 and 76.13 percent, respectively while cytosolic AST activity from cerebellum increased by 28.05 percent. The mitochondrial AST activity lowered in olfactory lobes (by 72.45 percent), cerebrum (by 78 percent), cerebellum (by 49.56 percent) and medulla oblongata (by 69.30 percent). In vitro studies also showed increase in brain tissue proline and decrease in glutamate levels. In vitro studies indicated that proline has direct inhibitory effect on these enzymes and glutamate levels in brain tissue showed positive correlation with AST and ALT activities. Acid phosphatase (ACP) activity reduced significantly in olfactory lobes (40.33 percent) and cerebrum (20.82 percent) whereas it elevated in cerebellum (97.32 percent) and medulla oblongata (76.33 percent). The histological studies showed degenerative changes in brain. Following proline treatment, the animals became sluggish and showed low responses to tail pricks and lifting by tails and showed impaired balancing. These observations indicate influence of proline on AST, ALT and ACP activities of different brain regions leading to lesser synthesis of glutamate thereby causing neurological dysfunctions.