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F Di Lisa

Publications and source records attributed to F Di Lisa.

At least 55 records · Page 3Linked to original sources
PubMed1989

Carnitine: metabolism and clinical chemistry.

In man carnitine is synthesized from proteic trimethyllysine in liver, brain and kidney. Muscles which contain approximately 98% of carnitine must take it up from the blood in an exchange process with endogenous deoxycarnitine, the immediate precursor of carnitine. Uneven organ distribution of the enzymes catalyzing carnitine synthesis further implies an inter-organ transport of the intermediates. Assay of these intermediates in blood may assist causal definition of carnitine deficiency syndromes. Besides catalyzing the transport of long-chain acyls in mitochondria, carnitine is necessary for the export of intra-mitochondrially produced short-chain acyls and for trapping and elimination of unphysiological acyls (benzoic, pivalic, valproic acids etc.). Unlike the corresponding acyl-CoA, carnitine esters are capable of diffusing across cellular membranes, and may be eliminated in urine, distributed in tissues or both. Assay of physiological and unphysiological carnitine esters in urine is necessary for the diagnosis of carnitine insufficiencies.

Biological Transport↗
PubMed1989

Ca2+-mediated action of long-chain acyl-CoA on liver mitochondria energy-linked processes.

The decrease of steady-state transmembrane potential (delta psi) and loss of accumulated Ca2+ are magnified if palmitoyl-CoA is added to rat liver mitochondria exposed to Ca2+ and phosphate. The extent of this damage increases with increasing concentration of long-chain acyl-CoA. Addition of L-carnitine with or without the addition of palmitoyl-CoA considerably delays the deenergization. In the latter case, there is a substantial decrease in the assayed endogenous long-chain acyl-CoA content. This protective action of L-carnitine is abolished by L-aminocarnitine, a powerful inhibitor of carnitine palmitoyl transferase (palmitoyl-CoA: L-carnitine O-palmitoyltransferase, EC 2.3.1.21.). The removal of Ca2+ by EGTA, or the inhibition of its uptake by Ruthenium red or Mg2+ further enhances the degree of protection.

Acyl Coenzyme A↗
PubMed1988

Modification of the xanthine-converting enzyme of perfused rat heart during ischemia and oxidative stress.

The reversible and irreversible conversion of xanthine dehydrogenase to xanthine oxidase during ischemia/reperfusion and oxidative stress induced by hydrogen peroxide or diamide and its relationship with glutathione and protein SH groups were studied. The direct spectrophotometric measurement of the various forms of the xanthine-converting enzyme indicates that, in the fresh rat heart or after normoxic perfusion, there always is a basal level of 80% xanthine dehydrogenase and 20% of xanthine oxidase (15% irreversible and 5% reversible) that could contribute to the background production of free radicals. There is no significant increase of irreversible xanthine oxidase during ischemia nor during reperfusion. After global ischemia the reversible oxidase shows almost no increase while, when ischemia is followed by reperfusion, there is a limited increase (less then 9%) of the reversible xanthine oxidase. In the latter conditions there is a decrease of glutathione and of SH groups of about 70% and 25%, respectively. Perfusion for 1 h with oxidizing agents like hydrogen peroxide (60 microM) or diamide (100 microM) determines a marked conversion of xanthine dehydrogenase to reversible xanthine oxidase of about 40% and 60%, respectively; this oxidase activity partially reconverts to the dehydrogenase after withdrawing the oxidizing agents from the perfusion medium. The level of irreversible xanthine oxidase remains unchanged in all the conditions tested. Both hydrogen peroxide and diamide induce a strong decrease in SH groups and depletion of glutathione. The xanthine dehydrogenase----xanthine oxidase conversion thus appears to be sensitive to the redox state of thiol groups.

Animals↗
PubMed1987

Transport and function of L-carnitine and L-propionylcarnitine: relevance to some cardiomyopathies and cardiac ischemia.

Carnitine, an essential cofactor in fatty acid oxidation, plays a central role in myocardial metabolism. Interpretation of the biochemical features of disturbed myocardial function, particularly in ischemia, may be facilitated by understanding carnitine biosynthesis, transport and function. Biosynthesis: In man, deoxycarnitine, the immediate precursor of carnitine, is synthesized in all tissues, whereas the last step, the conversion of deoxycarnitine into carnitine may only take place in liver, kidney and brain (Figs. 1 and 2). Deoxycarnitine formed by organs like muscle or heart is released into the plasma, taken up by liver and kidney, converted into carnitine which is secreted into the bloodstream to be taken up by heart or muscle (Fig. 2). Carnitine transport and cellular function: The myocardial uptake of carnitine against a large concentration gradient (Table 1) occurs in an 1:1 exchange-diffusion process. Under physiological conditions, intracellular deoxycarnitine is exported and extracellular carnitine is imported. According to this model, myocardial carnitine deficiency may be due either to a functional alteration of the sarcolemmal carnitine carrier or to a deficient synthesis of deoxycarnitine. D-carnitine, acetylcarnitine and long-chain acylcarnitine esters are also transported by the carrier at different rates. This might account for the release of endogenous acylcarnitines accumulated in anoxic or ischemic conditions, contributing to the cardioprotective effect of carnitine by reduction in intracellular long-chain acyl-coenzyme A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Action of spermine on phosphate transport in liver mitochondria.

Spermine, at concentrations similar to those normally present in the cytosol of liver cells, facilitates the transport of phosphate into mitochondria and thus its accumulation within the matrix space. Both mersalyl and N-ethylmaleimide (NEM) inhibit phosphate influx either in the absence or in the presence of spermine. These inhibitors also inhibit, but only partially, the efflux from mitochondria of phosphate generated within the matrix space by the hydrolysis of ATP induced by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) or the valinomycin-K+ system. The inhibition of phosphate efflux by both mersalyl and NEM is almost completely removed, unlike that of phosphate influx, by spermine. The possibility that spermine may induce phosphate efflux by damaging mitochondrial membranes and consequently inducing an unspecific permeability to phosphate is excluded by the full restoration of transmembrane potential once FCCP has been removed by albumin. Since spermine does not react with either thiol groups or thiol group reagents, the simplest explanation of the reported results is that the pathway of phosphate efflux is distinct from that of phosphate influx.

Animals↗
PubMed1986

Myocardial recovery during post-ischaemic reperfusion: effects of nifedipine, calcium and magnesium.

We studied the effects of various interventions introduced at the time of post-ischaemic reperfusion on mechanical activity, tissue and mitochondrial calcium, mitochondrial function and tissue ATP and CP of isolated perfused rabbit hearts. These interventions were: nifedipine, low calcium (0.75 mM, 0.15 mM and 0.05 mM), high magnesium (15 mM) and high magnesium (15 mM) with low calcium (0.75 mM). Ischemia was induced by abolishing coronary flow for 60 min, followed by 30 min of reperfusion. The results indicate that nifedipine when given during reperfusion had no protective effect, whilst it was beneficial when administrated before ischaemia. Lowering calcium content of the perfusate during reperfusion may be advantageous, depending on the degree of calcium reduction. Reperfusion with high magnesium reduced the mitochondrial calcium overload and maintained the mitochondrial ATP-producing capacity but failed to modify the increase of tissue calcium and of diastolic pressure. Lowering calcium content in the presence of high magnesium resulted in better protection. These data suggest that the conditions of reperfusion may influence the capacity of myocardial recovery.

Adenosine Triphosphate↗
PubMed1985

Stabilising action of carnitine on energy linked processes in rat liver mitochondria.

Rat liver mitochondria exposed to stressing conditions - ageing at room temperature, incubation in the presence of t-butyl hydroperoxide or damaging concentrations of Ca2+ and phosphate- undergo a rapid fall in their membrane potential (delta psi) with a concomitant release of endogenous Mg2+ and accumulated Ca2+. Addition of L-carnitine to the incubation medium considerably delays mitochondrial deenergization. A similar, though lower, protection has also been observed in L-carnitine pretreated and subsequently washed rat liver mitochondria. Furthermore mitochondria isolated from livers of starved rats, treated with L-carnitine 30 minutes before death and exposed to the same stressing conditions show similar delay in the decrease of delta psi and concurrent energy linked processes as compared with untreated animals. Both the in vitro and in vivo results strongly indicate that the stabilising action of L-carnitine on liver mitochondria is due to the removal of membrane bound long chain acyl CoA.

Animals↗
PubMed1985

Uptake of spermine by rat liver mitochondria and its influence on the transport of phosphate.

Spermine, a polyamine present in the mammalian cells at rather high concentration, has, among other actions, a remarkable stabilizing effect on mitochondria, functions which have generally been attributed to the capability of this and other polyamines to bind to membrane anionic sites. In the present paper evidence is provided that at physiological concentrations spermine may also be transported into rat liver mitochondrial matrix space, provided that mitochondria are energized and inorganic phosphate is simultaneously transported. The close dependence of spermine transport is also demonstrated by the concurrent efflux of spermine and inorganic phosphate when mitochondria preloaded with the two ionic species are deenergized either with uncouplers or respiratory chain inhibitors. Furthermore, Mersalyl, the known inhibitor of phosphate transport, prevents both spermine uptake and release. Mg2+ inhibits the transport of spermine conceivably by competing for the some binding sites on the mitochondrial membrane. The physiological significance of these results is discussed.

Animals↗
PubMed1984

Biochemical derangements in ischemic myocardium: the role of carnitine.

The most important biochemical derangements in ischemic myocardium are the decrease of energy rich phosphates (ATP and phosphocreatine) and intracellular acidosis, both of which contribute to a rapid loss of the contractile function. How and to which extent the alterations of carbohydrate and lipid metabolism are involved in these derangements is briefly discussed. In conditions of oxygen restriction the synchronism between the cytosolic and mitochondrial phase of carbohydrate metabolism is disrupted and beta-oxidation of long chain fatty acids is prevented. Consequently less ATP and more lactate is produced and fatty acids accumulate together with their activation products, acyl CoA in particular. In ischemia free carnitine is also decreased and the carnitine dependent functions (acyl transfer across mitochondrial membrane and pyruvate and alpha ketoglutarate dehydrogenase stimulation) impaired. The meaning of the altered carnitine dependent functions is considered together with the possible (demonstrated and supposed) metabolic effects of carnitine administration in cardiac ischemia.

Acyl Coenzyme A↗
PubMed1983

On the mechanism of citrate and isocitrate protective action on rat liver mitochondria.

Both citrate and isocitrate prevent the damage (efflux of endogenous Mg2+ and pyridine nucleotides, decay of delta psi and release of accumulated Ca2+) induced in rat liver mitochondria by Ca2+ and phosphate fluxes. Addition of fluorocitrate suppresses the action of isocitrate, but not that of citrate. The same results have been obtained with mitochondria isolated from animals treated with fluoroacetate. It is suggested that citrate directly and isocitrate by prior conversion into citrate exert the protective action by chelating and retaining Mg2+ within the mitochondria.

Animals↗