Effect of injected glucagon or fatty acids on mitochondrial ATPase (original) (raw)
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Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1971
Liver mitochondria isolated from essential fatty acid-deficient rats oxidize in hypotonic solution exogenous NADH more slowly than mitochondria isolated from normal rats. Because this difference becomes apparent with the onset of the essential fatty acid deficiency, and disappears when the deficient animal is fed a normal (essential fatty acid-sufficient) diet it appeared that measurement of NADH oxidation rates might be the basis of an in vitro assay for essential fatty acid deficiency. However, no close correlation between the pattern of mitochondrial fatty acid unsaturation and the ability to oxidize NADH could be observed. Indeed, diets could be manipulated in several ways to produce conditions wherein mitochondria presumably sufficient in essential fatty acids exhibited either a low capacity to oxidize NADH, similar to essential fatty acid-deficient mitochondria, or the reverse. It is concluded that the pattern of mitochondrial fatty acid unsaturation may vary widely without affecting the capacity to oxidize NADH, and presumably, therefore, the specific stability of the membrane.
Mechanisms of Ageing and Development, 2001
Previous comparative studies have shown that long-lived animals have lower fatty acid double bond content in their mitochondrial membranes than short-lived ones. In order to ascertain whether this trait protects mitochondria by decreasing lipid and protein oxidation and oxygen radical generation, the double bond content of rat heart mitochondrial membranes was manipulated by chronic feeding with semi-purified AIN-93G diets rich in highly unsaturated (UNSAT) or saturated (SAT) oils. UNSAT rat heart mitochondria had significantly higher double bond content and lipid peroxidation than SAT mitochondria. They also showed increased levels of the markers of protein oxidative damage malondialdehyde-lysine, protein carbonyls, and N e -(carboxymethyl)lysine adducts. Basal rates of mitochondrial oxygen radical generation were not modified by the degree of fatty acid unsaturation, but the rates of H 2 O 2 generation stimulated by antimycin A were higher in UNSAT than in SAT mitochondria. These results demonstrate that increasing the degree of fatty acid unsaturation of heart mitochondria increases oxidative damage to their lipids and proteins, and can also www.elsevier.com/locate/mechagedev Abbre6iations: SAT -group fed saturated diet; UNSAT -group fed unsaturated diet; MDAmalondialdehyde; MDA-Lys -MDA-lysine; CML -N e -(carboxymethyl)lysine. : S 0 0 4 7 -6 3 7 4 ( 0 1 ) 0 0 2 1 4 -7
Life Sciences, 2018
Aims: Our earlier studies revealed the cardio-protective effects of oleic acid, a monounsaturated fatty acid, against adrenaline induced myocardial injury. Moreover, it has been found to possess antioxidant properties. Thus, in the present study we have investigated the protective role of oleic acid on adrenaline induced mitochondrial dysfunction in vitro in rat heart mitochondria. Main Methods: Isolated rat cardiac mitochondria was incubated in vitro with adrenalinebitartrate alone and with graded doses of oleic acid. Biomarkers of oxidative stress, mitochondrial Krebs cycle enzymes and respiratory chain enzymes along with mitochondrial morphology, membrane potential as well as intactness were analyzed. Isothermal titration calorimetric studies with pure adrenaline and oleic acid was also carried out.
The Journal of Nutritional Biochemistry, 1995
This study was designed to examine whether n-3 and n-6 polyunsaturated fatty acids (PUFA) at a very low level in the diet (about 0.2%) may alter the fatty acid composition of mitochondrial outer membranes and the characteristics of carnitine pa~mitoyltransferase I (CPT I) activity in the liver of normal Wistar rats. The animals were fed diets containing deferent oil mixtures (5% wtlwt) with the same ratio of n-6ln-3 fatty acids sapplied either as fish oil or arachidonic acid concentrate. The cholesterol content of the mitochondrial outer membranes from liver was similar for all diets, while the percentage of 22:6n-3 and 20:4n-6 in phospholipids was enhanced with the diets conta~ning~sh oil and arachidonic acid, respectively. With the fish oil diet, CPT I was found to be less sensitive to ~lonyI-boa inhibition. When ani~ls werefed the diet containing ararhidoni~ acid, the enzyme activity was lowered, but its sensitivity to malortyl-CoA was unaffected. In this group, the liver mitochondrial content appeared to be reduced both when expressed per unit of weight and on a whole organ basis. The results show that a low level of dietaty PUFAs supplied to normal Wistar rats is sufficient to injluence the content of n-3 and n-6 PUFAs in mitochondrial outer membranes and to alter some of the characteristics of CPT I. However, the data suggest that factors other than the PUFA content of membrane phospholipids must be involved in mediating the changes in CPT I kinetic characteristics observed in this study.
European Journal of Biochemistry, 1982
Previous work has shown that dibutyryl adenosine 3',5'-monophosphate (Bt,cAMP) markedly activates ketogenesis from fatty acids released during the mobilization of cytoplasmic triacylglycerol-rich vesicles in the chick liver cell. In the present investigation, activation of the formation of [I4C]acetoacetate and 3-['4C]hydroxybutyrate from [l-'4C]oleate by the cyclic nucleotide was shown to occur at two mitochondrial sites: (a) the L-(-)-carnitinedependent translocation of the fatty acid across the inner mitochondrial membrane and (b) the intramitochondrial metabolism of acetyl-CoA. The hypothesis was tested that cAMP regulates ketogenesis and fatty acid synthesis by controlling acetyl-CoA flux at the mitochondrial branch-point leading into the 3-hydroxy-3-methylglutaryl-CoA cycle or to citrate formation. Bt,cAMP caused an immediate activation of acetoacetate formation and a concomitant inhibition of fatty acid synthesis from acetate. Evidence is presented that these effects are due to a cyclic-nucleotide-induced fall in the mitochondrial concentration of oxaloacetate. An assay for oxaloacetate, sufficiently sensitive to analyze extracts of cells in monolayer culture, was employed. With this assay, Bt,cAMP was shown to cause a > 90 % decrease in cellular oxaloacetate concentration. The calculated level to which intramitochondrial oxaloacetate fell was below the
Stimulation of potassium cycling in mitochondria by long-chain fatty acids
Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2003
Nonesterified long-chain fatty acids (myristic, palmitic, oleic and arachidonic), added at low amounts (around 20 nmol/mg protein) to rat liver mitochondria, energized by respiratory substrates and suspended in isotonic solutions of KCl, NaCl, RbCl or CsCl, adjusted to pH 8.0, induce a large-scale swelling followed by a spontaneous contraction. Such swelling does not occur in alkaline solutions of choline chloride or potassium gluconate or sucrose. These changes in the matrix volume reflect a net uptake, followed by net extrusion, of KCl (or another alkali metal chloride) and are characterized by the following features: (1) Lowering of medium pH from 8.0 to 7.2 results in a disappearance of the swelling-contraction reaction. (2) The contraction phase disappears when the respiration is blocked by antimycin A. (3) Quinine, an inhibitor of the K + /H + antiporter, does not affect swelling but suppresses the contraction phase. (4) The swelling phase is accompanied by a decrease of the transmembrane potential and an increase of respiration, whereas the contraction is followed by an increase of the membrane potential and a decrease of oxygen uptake. (5) Nigericin, a catalyst of the K + /H + exchange, prevents or partly reverses the swelling and partly restores the depressed membrane potential. These results indicate that long-chain fatty acids activate in liver mitochondria suspended in alkaline saline media the uniporter of monovalent alkali metal cations, the K + /H + antiporter and the inner membrane anion channel. These effects are presumably related to depletion of mitochondrial Mg 2 + , as reported previously [Arch. Biochem. Biophys. 403 (2002) 16], and are responsible for the energy-dissipating K + cycling. The uniporter and the K + /H + antiporter are in different ways activated by membrane stretching and/or unfolding, resulting in swelling followed by contraction.
Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1996
Liver mitochondria isolated from controls or polyunsaturated fatty acid (PUFA) deficient rats were studied for oxidative phosphorylation. A PUFA-deficient diet led to a dramatic change in the fatty acid composition of mitochondrial lipid content, similar to that reported in the literature. Besides the changes in lipid composition, mitochondrial volume was enlarged (+ 45% in state 4 and two-fold in state 3). State 4 respiration was increased together with a decrease in protonmotive force. The non-ohmicity of the relationship between non-phosphorylating respiration and protonmotive force was more pronounced in the PUFA-deficient group. State 3 oxygen consumption as well as the rate of ATP synthesis showed no difference between the two groups, whereas the protonmotive force decreased substantially in mitochondria from PUFA-deficient animals. In contrast, ATP/O ratios were decreased in the PUFA-deficient group when determined at subsaturating ADP concentration. Taken together, these results are in agreement with both an increased non-ohmic proton leak and an increased redox slipping. The relative importance of these two effects on the overall efficiency of oxidative phosphorylation depends on both the rate of oxidative phosphorylation and the maintained protonmotive force. Hence, in isolated mitochondria the respective role of each effect may vary between state 4 and state 3.