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N Siliprandi

Publications and source records attributed to N Siliprandi.

At least 55 records · Page 3Linked to original sources
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

L-carnitine effect on halothane-treated mitochondria.

Addition of halothane to the incubation medium is shown to lower respiratory control and transmembrane potential and to increase ATPase activity in isolated rat liver mitochondria. Evidence is presented that L-carnitine is able to substantially decrease the negative effects of halothane on the energy-linked processes of mitochondria. The effects of halothane and the protective action of L-carnitine are discussed in the light of a possible involvement of long-chain acyl CoA in the unpairing of mitochondrial energy-linked functions.

Acyl Coenzyme A↗
PubMed1986

Involvement of long-chain acyl CoA in the antagonistic effects of halothane and L-carnitine on mitochondrial energy-linked processes.

Incubation of rat liver mitochondria in the presence of halothane induced a consistent impairment of mitochondrial oxidative phosphorylation without significantly affecting the steady-state of transmembrane electrical potential. These alterations of mitochondrial energy-linked processes were associated with a consistent accumulation of long-chain acyl CoA. Addition of L-carnitine partially prevented the effects of halothane on oxidative phosphorylation and completely abolished the halothane-induced long-chain acyl CoA accumulation. The possibility is discussed that the damaging action of halothane on mitochondrial functions might be partially ascribed to the noxious action of the excess of long-chain acyl CoA induced the anesthetic.

Acyl Coenzyme A↗
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↗
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↗
PubMed1984

Pantethine and pantothenate effect on the CoA content of rat liver.

The role of pantethine as a precursor of CoA in rat liver has been examined. It has been demonstrated that pantethine induces a significant increase in the total CoA content both in perfused liver and in liver homogenate, while it fails to affect the mitochondrial CoA content when added to isolated mitochondria. Pantethine is more efficient than pantothenate in inducing the synthesis of CoA in rat liver, even in the presence of added cysteine. The possible metabolic implications are discussed.

Animals↗
PubMed1983

Studies on the transport of carnitine in the brain using synaptosomes isolated from guinea-pig cerebral cortex.

Synaptosomes isolated from guinea pig cerebral cortex accumulate L-carnitine from the medium in an active process, dependent on the sodium gradient across the plasma membrane and on (Na+ + K+)-ATPase activity. L-Carnitine uptake is inhibited by oxidative phosphorylation uncouplers and by ouabain, a known inhibitor of (Na+ + K+)-ATPase. In addition, the omission of Na+ or its replacement by Li+ inhibited the transport, which was also competitively inhibited by gamma-aminobutyrate. The kinetics of carnitine uptake show that the overall process would consist of two components: a passive diffusion and a carrier-mediated transport which is saturated at 1-2 mM carnitine concentration.

Animals↗
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↗
PubMed1983

On the mechanism by which Mg2+ and adenine nucleotides restore membrane potential in rat liver mitochondria deenergized by Ca2+ and phosphate.

The presence of ATP or ADP in the incubation medium prevents the collapse of membrane potential induced by external Ca2+ and phosphate. The same adenine nucleotides are unable to restore collapsed membrane potential unless Mg2+ are also added. Bongkrekate is also able to prevent the effects of external Ca2+ and phosphate and when added after membrane potential has collapsed strongly potentiates the restorative action of ATP or ADP. Atractyloside has an opposite effect.

Adenine Nucleotides↗
PubMed1983

On the relationship between calcium and phosphate transport, transmembrane potential and acetoacetate-induced oxidation of pyridine nucleotides in rat-liver mitochondria.

Acetoacetate addition to rat liver mitochondria induces a complete oxidation of pyridine nucleotides, a collapse of membrane potential, a release of mitochondrial Ca2+ and a loss of respiratory control only in the presence of external phosphate. Acetoacetate also enhances the efflux of mitochondrial Mg2+ promoted by phosphate. All these effects are not only prevented but also reversed, except the oxidation of pyridine nucleotides, by the combined addition of Mg2+, ADP and dithioerythritol to damaged mitochondria. It is concluded that acetoacetate, through the oxidation of mitochondrial pyridine nucleotides, potentiates the action of phosphate in altering the mitochondrial permeability barrier, which is closely dependent on the maintenance of membrane thiol groups in a reduced form.

Acetoacetates↗
PubMed1983

Favorable effects of L-carnitine treatment on hypertriglyceridemia in hemodialysis patients: decisive role of low levels of high-density lipoprotein-cholesterol.

Twenty-nine hemodialyzed patients with hypertriglyceridemia were given L-carnitine (20 mg/kg iv at the end of each dialysis) for 120 days and then placebo for the same duration in order to evaluate the lipid-lowering effects of the metabolite. A dramatic reduction in triglyceride levels was observed only in the group of patients (n = 12) with high basal triglyceride values, low levels of high-density lipoprotein-cholesterol, and with apoprotein A at the lower limit of normal range. During L-carnitine treatment these patients exhibited significantly increased high-density lipoprotein-cholesterol and apoprotein A. No rebound effects were observed. L-Carnitine did not provoke changes in the lipid parameters in the group (n = 17) with high basal triglyceride values, and normal high-density lipoprotein-cholesterol and apoprotein A. Hematocrit values increased in all the 29 patients during L-carnitine treatment. At the end of the experimental protocol, L-carnitine dosage was increased to 60 mg/kg iv (at the end of each dialysis) in four patients of the group of nonresponders and prolonged for 60 days. This produced a considerable reduction in triglyceride levels. The above results suggest that L-carnitine can be effective in the management of hypertriglyceridemia in the hemodialyzed patient especially when low high-density lipoprotein-cholesterol levels are present.

Adult↗