Victor N. Konji

Interaction of benzoquinones with mitochondria interferes with oxidative phosphorylation characteristics

Studies with four benzoquinones, viz. juglone, embelin, maesaquinone and maesanin, on rat liver mitochondria oxidative phosphorylation have been carried out. Three of the benzoquinones are uncouplers in the order juglone > maesoquinone > embelin, while maesanin is an inhibitor of electron transport and oxidative phosphorylation.

Effect of different doses and routes of administration of embelin on plasma testosterone levels

Embelin has been shown to have potential for fertility regulation in male mammals. To further investigate this the effect of varying doses of embelin administered through different routes on plasma testosterone levels in sexually mature male white New Zealand rabbits was studied. An intramuscular injection of 5 mg/kg body weight of embelin caused a 54% declined in testosterone levels from 8.35±0.4 nmol (pre‐treatment) to 3.8±0.15 nmol/L (post‐treatment); mean±SEM. When orally administered as a suspension of 10 mg/kg body weight embelin caused a significant (p <0.001) lowering in the hormone levels from 12.2±0.70 nmol/L (pre‐treatment) to 4.55±0.35 nmol/L after treatment. But when administered orally as a 50 mg base tablet, a decline of 40% in testosterone levels was observed. Subcutaneous administration of 20 mg/kg body weight of embelin caused a 12.4% decline in the hormone levels from 26.6±1.30 nmol/L (pre‐treatment) to 18.9±1.30 nmol/L after treatment. The decline in the testosterone levels when embelin was administered either intramuscularly or as a suspension orally was rapid, while a tablet or subcutaneous injection caused a gradual decline. From the study it was concluded that oral administration offered the most effective and convenient route of delivery of embelin.

Enzyme activities in the fat body of the tsetse fly Glossina morsitans and the fleshfly Sarcophaga tibialis in relation to proline metabolism

Enzymes were assayed in the fat body of the tsetse fly Glossina morsitans and compared with those in the fat body of the fleshfly Sarcophaga tibialis. Alanine aminotransferase, 3-hydroxyacyl-CoA dehydrogenase, NADP-linked isocitrate dehydrogenase and proline synthetase were much more active in G. morsitans. NADP-linked malic enzyme, pyruvate carboxylase, citrate synthase and aconitase were also more active in G. morsitans, but α-oxoglutarate dehydrogenase, fumarase, malate dehydrogenase and various glycolytic enzymes were more active in S. tibialis. Pyruvate carboxylase was mainly mitochondrial in the fat body of both insects, whereas NADP-linked malic enzyme was cytoplasmic. Alanine aminotransferase and NADP-linked isocitrate dehydrogenase were more predominantly mitochondrial in G. morsitans than in S. tibialis. In the fat body of G. morsitans the Km values of pyruvate carboxylase for pyruvate and bicarbonate were quite low, whereas those of NADP-linked malic enzyme were high. Alanine aminotransferase from G. morsitans fat body had lower apparent Km values for alanine and α-oxoglutarate than flight muscle enzyme from the same species. The proline synthesizing potential of G. morsitans fat body is discussed. It is suggested that the pathway involves the enzymes pyruvate carboxylase and NADP-linked isocitrate dehydrogenase.

Respiratory activity of isolated liver Mitochondria following Trypanosoma congolense infection in rabbits: the role of thyroxine.

1. The effect of trypanosome infection on rabbit liver mitochondrial oxidative phosphorylation was investigated, with and without thyroxine replacement. 2. State 3 respiration, respiratory control ratio (RCR) and ADP/O ratio were significantly reduced in mitochondria from trypanosome-infected animals whereas there was no change in state 4 respiration. 3. State 3 respiration, RCR and ADP/O ratio were not significantly altered in trypanosome-infected animals given thyroxine replacement therapy. 4. Trypanosome infection leads to impairment of mitochondrial integrity, apparently through lowered thyroxine levels. Replacement of thyroxine therefore sustains optimal mitochondrial respiratory activity.

Defects in resting metabolic rates and mitochondrial respiration in Kwashiorkor and dietary obese rats

SummaryResting metabolic rates have been measured and compared with hepatic mitochondrial respiration in Kwashiorkor and diet-induced obese weaned rats. In Kwashiorkor, resting metabolic rate was 21% lower than the value of controls, while that of the obese rats was 14% higher than in control animals. The resting metabolic rate for Kwashiorkor animals was 50% of the predicted basal metabolic rate (BMR), whereas that of the obese rats was 23% higher than the predicted BMR. The mitochondrial oxygen consumption patterns, using malate plus glutamate or succinate as respiratory substrates, revealed that the resting respiration (state 4) was 23.9% higher in Kwashiorkor and 29.1% higher in obese animals, while the active (state 3) respiration was 34.8% lower in Kwashiorkor and 43.3% lower in obese rats compared to controls. The respiratory control ratios (RCR) were 51.1% and 43.8% in Kwashiorkor and obese rats, respectively, relative to the values in control rats. It is concluded from these studies that Kwashiorkor disease and diet-induced obesity appear to interfere with oxygen utilization at the level of state 3 mitochondrial respiration, which is markedly decreased when compared to the values for control animals.

Proline synthesis in the fat body of the tsetse fly Glossina morsitans, and its stimulation by isocitrate

Abstract The in vitro synthesis of proline from glutamate was followed in fat body homogenates from the tsetse fly Glossina morsitans . Rates of synthesis were much higher in freeze-thawed or sonicated homogenate than in untreated homogenate. Synthesis in the presence of added glutamate was significantly stimulated by addition of NADH, NADPH and ATP, the effects of these coenzymes being approximately additive. Isocitrate stimulated proline production in the presence of glutamate. This effect was most marked when no coenzymes were added, but was observed also when all three coenzymes were present. α-Oxoglutarate was without action. α-Oxoglutarate was produced when freeze-thawed fat body homogenate was incubated with isocitrate. Production was enhanced when glutamate was also present, and enhanced further by the combined addition of NADH, NADPH and ATP. The role of isocitrate in proline synthesis is discussed. It is suggested that synthesis from glutamate utilizes NADPH generated by the oxidation of isocitrate through the mitochondrial NADP-isocitrate dehydrogenase reaction.