Changes induced by ischemia on some cerebral enzymatic activities related to energy transduction and amino acid metabolism

Abstract

The maximal rate of some cerebral enzymatic activities related to energy transduction (hexokinase; phosphofructokinase; lactate dehydrogenase; citrate synthase; malate dehydrogenase; total NADH-cytochrome c reductase; cytochrome oxidase), amino acid metabolism (glutamate decarboxylase; glutamate dehydrogenase) and cholinergic metabolism (acetylcholine esterase) were tested in the cerebral cortex and in sub-cortical area of rats. The evaluations were performed both in the homogenate in toto and in the crude mitochondrial fraction, before and after a postdecapitative normothermic ischemia of 5, 10, 20, and 40 min duration. The results are discussed also with respect to the pharmacological pretreatment with two biological substances which may modulate amino acid (L-alanine) and phospholipid metabolism (CDP-choline). The analysis of the present data suggests the occurrence in brain tissue of a variety of interrelated factors implicated in the ischemia-induced changes of the maximal rate of the enzymatic activities related to the energy transduction. These include: (a) rearrangement of the enzymatic activities because of the changed metabolic and chemico-physical condition; (b) decrease in the activity of enzymes related to the electron transfer chain and glycolysis; (c) changes in enzymes related to mitochondrial membranes. The effects of in vivo administration of alanine or CDP-choline, even if significant, are not consistent throughout the time period studied.

Effect of Ageing and Ischemia on Enzymatic Activities Linked to Krebs’ Cycle, Electron Transfer Chain, Glutamate and Aminoacids Metabolism of Free and Intrasynaptic Mitochondria of Cerebral Cortex

“…In this context, ''physiological'' ageing has been found to modify enzyme activities differently in the mitochondria populations: increases in malate dehydrogenase, succinate dehydrogenase, NADHcytochrome c reductase (both total and rotenone sensitive) and glutamate-pyruvate transaminase in the heavy type of intra-synaptic mitochondria, whereas no changes were found in the other mitochondrial population studied [1] largely confirming results of the former investigations on normal ageing [2][3][4]. More pronounced abnormalities in mitochondria-linked enzyme activities were found under defined experimental conditions such as brain hypoxia and ischemia [5][6][7].…”

“…The different behaviour of enzymes depending on the subcellular fractions on which they are in vivo located, is not surprising, because the same plasticity was also observed for ATP-ases activities during ageing in synaptic plasma membranes [48][49][50], during the recovery from hypoxic hypoxia cycles [51][52][53] and in others models of cerebral ischemia [5,6,54].…”

In vivo 13C saturation transfer effect of the lactate dehydrogenase reaction

“…The in vivo unidirectional lactate 3 pyruvate flux determined in this study can be compared to the LDH activities determined in samples of rat brain homogenate obtained from normal rats. In the pyruvate 3 lactate direction, the activity of LDH was determined to be 107-119 mol/g/min (31,32). In the lactate 3 pyruvate direction (measured in this study), the whole-brain LDH activity was determined to be 32 mol/g/min using 19 mM lactate, 1 mM NAD ϩ at pH ϭ 8.5 and 25°C (33).…”

Time course of changes in brain energy metabolism of the rat after microsphere-induced cerebral embolism.

“…The ATP and CP levels of both hemispheres isolated from sham-operated rats were slightly, but significantly lower than the initial. Numbers of experiments for microsphere administered rats were 17 (no operation) and 9 (each on the 1st, 3rd, 5th and 7th days after the operation), whereas those for sham-operated rats were 7 (on the 1st day), 8 (on the 3rd day), 7 (on the 5th day) and 6 (on the 7th day). *Significantly different from the initial value (P < 0.05).…”

“…The results provided information on a useful model for therapeutic studies of anti-ischemic agents in the brain. (1), hypoxia induced by artificial ventilation with an oxygen-deficient gas mixture (2-5), or hypercapnia provoked by ventilation with carbon dioxide-enriched gas mixture (6)(7)(8)(9). In general, most animals subjected to these oxygen-deficient conditions do not survive for more than one day.…”