Decrease In Succinate Research Articles

Decrease of phosphorylating oxidation and increase of heat producing NADH oxidation in rat liver mitochondria during life-span prolongation of rats by calorie-restricted diet

The influence of calorie-restricted diet, initiated at weaning, on some of the oxidative processes in liver homogenates and isolated mitochondria of 2-, 3-, 4-, 24-, 35- and 45-month-old male Wistar rats was studied in comparison with control ad libitum-fed 1–2 day-old rats and 0.5-, 1-, 2-, 3-, 4- and 24-month-old rats. It was shown that a calorie-restricted diet (at 37% of the ad libitum calorific level) did not change the rate of succinate oxidation coupled with oxidative phosphorylation in homogenates, but resulted in a decrease of succinate, glutamate plus malate and β-hydroxybutyrate oxidation and cytochrome c-oxidase activity in isolated mitochondria without any uncoupling of oxidative phosphorylation or change in cytochrome content in the mitochondria. On the other hand, a significant increase in mitochondrial rotenone-insensitive NADH oxidation and a higher level mass/body mass ratio in rats under the calorie-restricted diet was established. It may be considered that the activation of a heat-producing mechanism is a very important physiological function in such a condition.

Mitochondrial effect of orally administered dibutyl phthalate in rats.

Rats fed a diet containing 5% dibutyl phthalate (DBP) for 35 to 45 days revealed growth depression, liver enlargement and testicular atrophy. These effects were accompanied by inhibited respiration in liver mitochondria. This inhibition was caused by the decrease of succinate and pyruvate dehydrogenases activities rather than by the inhibition in the other respiratory redox components, in the coupling process or in the energy-transfer process. Such inhibitory effect was also observed in vitro, where nealy the same inhibitory potency as that found in vivo, occurred at a concentration less than 100μM DBP for the respiration and 150μM DBP for the dehydrogenase activities. The present study also showed that DBP can be easily taken up into the matrix of mitochondria and that it directly affects succinate dehydrogenase without altering the transport system for succinate.

In vivo sub-acute physiological stress induced by Sumithion on some aspects of oxidative metabolism in the fresh water crab

Specimens of fresh water crab, Oziotelphusa senex senex were exposed to sub-lethal concentration (25 % of LC50/48 hr) of Sumithion for 7 days. Sumithion was found to inhibit the activity levels of acetylcholinesterase, succinate dehydrogenase,isocitrate dehydrogenase and pyruvate dehydrogenase, activate lactate dehydrogenase and cause accumulation of acetylcholine in the hepatopancreas and muscle. The increase in lactate dehydrogenase and the decrease in succinate, isocitrate and pyruvate dehydrogenases in these tissues indicate the development of anaerobic conditions and is interpreted as a functional adaptation to pesticide induced metabolic stress.

Ammonia toxicity mechanism in fish: Studies on rainbow trout ( Salmo gairdneri Rich.)

Salmo gairdneri specimens were exposed for 4–48 hr to various environmental un-ionized ammonia (UIA) concentrations. In the brain of NH 3-treated trout glutamate, GABA, total sugars, ATP, NADH, and succinate decrease, while tissue NH 3 content, glutamine, and lactate increase. In the liver total sugars, succinate, and lactate decrease, while tissue NH 3, glutamine, and the taurine/glycine ratio increase. Such variations depend upon exposure time and environmental UIA level. Ammonia toxicity mechanism in fish is discussed and compared with the one proposed in mammals. Further data obtained from overturned specimens suggest that in these animals a cerebral hypoxic phenomenon also occurs.

REGIONAL BRAIN LEVELS OF γ‐HYDROXYBUTYRATE IN HUNTINGTON'S DISEASE

Abstract—A highly sensitive electron capture gas chromatographic method was developed for quantitation of γ‐hydroxybutyrate (GHB) in tissue. This method involves an improved, extraction and purification procedure and a one‐step derivatization of GHB to the methyl ester‐O‐heptafluorobutyrate. As low as 5 ng of GHB in tissue was accurately quantitated by this method.By means of this improved method, endogenous levels of GHB in several regions of brains obtained post‐mortem from patients with Huntington's disease were determined, and compared with brain samples obtained post‐mortem from non‐neurological controls. The levels of GHB found in the caudate and substantia nigra obtained from Huntington's patients were significantly higher than the GHB levels found in similar regions of brain obtained from a non‐neurological control group. The content of GABA in the same choreic and control brain samples was also determined. No significant correlation between changes in GHB and GABA levels was observed although there was a trend towards an inverse relationship. The high level of GHR in Huntington's disease may be related to the decrease in succinate:oxidoreductase (EC 1.3.99.1) activity reported by Stahl & Swanson (1974).In two subjects (one control and one Huntington patient) the zonal distribution of GHB in substantia nigra was also determined. The zona reticulata from choreic brain contained a substantially higher level of GHB, whereas the zona compacta contained an amount similar to the level found in control brain.

Effects of chronic ethanol treatment upon rat liver mitochondria

Liver mitochondria of male Sprague-Dawley rats chronically treated with ethanol showed a similar depression (40–50 per cent) of oxygen uptake under state 4, state 3 and DNP-uncoupled conditions with succinate as substrate. Using β-hydroxybutyrate as the substrate, respiratory rates in states 4 and 3 were depressed, but the rate under DNP-uncoupled conditions was not. ADP: 0 ratios were depressed by 16 per cent with pyruvate but not with succinate. Upon closer examination of the electron transport chain in freeze-thawed mitochondria, several heretofore undetected defects were noted. These include similar depressions (41–46 per cent) in the oxidations of NADH, β-hydroxy-butyrate, malate or glutamate with cytochrome c as electron acceptor. These results suggest that defects do not occur at the level of substrate dehydrogenation but between NADH and cytochrome c. Other defects in the electron transport chain were observed: a 30 per cent decrease in NADH:ferricyanide reductase activity; a 38 per cent decrease in ubiquinone content and a 68 per cent decrease in succinate: cytochrome c reductase activity. However, the last result may not be attributed to effects upon succinic dehydrogenase per se, because succinate: DCIP reductase activity was unaltered. A 59 per cent depression of cytochrome c oxidase activity was also noted and must reflect a 44 per cent decrease in cytochrome aa 3 content, since K m and V max values were identical for control and ethanol-treated animals.

Energy-linked and energy-independent transhydrogenase activities in Escherichia coli vesicles

Active transport vesicles of Escherichia coli were shown to possess low levels of energy-independent and energy-dependent nicotinamide nucleotide transhydrogenase activities. Breakage of such vesicles in a French pressure cell resulted in a fraction which had an 8–10-fold increased respiration- and ATP-driven transhydrogenase activities. Stimulation of the ATPase activity in vesicles with Triton X-100 was also paralleled by a 2-fold increase in the energy-independent transhydrogenase. Disruption of the vesicles similarly resulted in increases in the energy-independent transhydrogenase, NADH and succinate oxidase activities but a decrease in succinate supported proline uptake. In the light of these findings, the ‘sidedness’ of the vesicle membranes is discussed.