Search PubMed⌕ Search

Biomedical subjects

J Swierczyński

Publications and source records attributed to J Swierczyński.

At least 19 recordsLinked to original sources
PubMed2001

[Adenine reutilization as a cause of increased ATP concentration in erythrocytes of patients with chronic renal failure].

Abnormalities of adenine nucleotide metabolism are observed in erythrocytes of patients with chronic renal failure (CRF) and the elevated ATP concentration is the most impressive one. In humans, adenine and/or adenosine reutilization is the only source of purine moiety used to erythrocyte adenine nucleotide synthesis. In the present study we have focused on the role of adenine as a substrate for the intraerythrocyte ATP production. 10 patients with CRF and 10 healthy volunteers (control group) were included into the study. Using HPLC, the measurements were performed in plasma and erythrocyte extracts. We observed a few fold higher adenine concentration in both plasma and erythrocytes of patients with CRF when compared with control group. There was also elevated an intraerythrocyte ATP concentration in the studied group of patients. Moreover, we have found a positive correlations between a) plasma creatinine concentration and plasma adenine concentration, b) plasma creatinine concentration and erythrocyte adenine concentration, c) plasma adenine concentration and intraerythrocyte ATP concentration. It appears that increased adenine reutilization could be a principle reason of the increased ATP synthesis in erythrocytes of patients with CRF.

Adenine↗
PubMed2001

[Renal replacement therapy results in correction of plasma and erythrocyte adenine nucleotide abnormalities in patients with chronic renal failure].

High concentration of intraerythrocyte ATP is a common phenomenon in patients with chronic renal failure (CRF). It is likely that this is a result of increased plasma concentration of adenine--one of purine moiety donors which is necessary for ATP synthesis. In the present study we monitored changes of both adenine and intraerythrocyte ATP concentration during renal replacement therapy. We have also estimated the influence of erythropoietin treatment. 4 groups of patients were included into the study: 22 patients with CRF, 22 patients on maintenance hemodialysis treatment (11 patients with EPO therapy), 19 patients after kidney transplantation (7 patients with insufficiency of transplanted kidney) and 26 healthy volunteers served as a control group. The measurements were performed in plasma and erythrocyte extracts using HPLC. Significant decrease of high plasma adenine concentration was observed after both HD session and successful kidney transplantation, however the achieved values were still higher than in healthy volunteers. Kidney transplantation resulted in a permanent decrease of plasma adenine concentration, but along with the deterioration of transplanted kidney function, the plasma adenine concentration reincreased. Also, it started to increase right after HD session had ended. On the other hand, the intraerythrocyte concentration of adenine and ATP after successful kidney transplantation and single HD session came back to normal values. Also in this case, along with the deterioration of transplanted kidney function, both studied parameters reincreased. We have not observed any significant influence of erythropoietin treatment on studied adenine nucleotide concentration in hemodialysis patients. The present study confirms the strong interrelationship between the adenine nucleotide metabolism abnormalities and the advancement of renal failure. The abnormalities intensify along with the disease progression and the renal replacement therapy results in partial their correction.

Adenine↗
PubMed2000

Differential effect of clofibrate on acetyl-CoA carboxylase mRNA level in rat white and brown adipose tissue.

Regulation of some lipogenic enzyme gene expression by clofibrate was studied in rat white and brown adipose tissue. In white adipose tissue the drug administration for 14 days to rats resulted in the increase in acetyl-CoA carboxylase, ATP-citrate lyase, and glucose 6-phosphate dehydrogenase mRNA levels. Opposing effect of clofibrate on the acetyl-CoA carboxylase, ATP-citrate lyase, and glucose 6-phosphate dehydrogenase mRNA levels was found in brown adipose tissue. These data indicate a tissue specificity of clofibrate action on lipogenic enzyme gene expression. The results presented in this paper provide further evidence that hypolipidaemia caused by the treatment with clofibrate cannot be related to the inhibition of fatty acid synthesis in white adipose tissue in rat.

Acetyl-CoA Carboxylase↗
PubMed1997

Unususal increase of lipogenesis in rat white adipose tissue after multiple cycles of starvation-refeeding.

The purpose of the study was to determine the response of liver and brown (BAT) and white (WAT) adipose tissue lipogenesis and total body weight in rats subjected to multiple cycles of 3 days of fasting and 3 days of refeeding. Rats fasted for 3 days showed significant reduction in body weight. These changes were reversed on 3 days' refeeding. Body weight was much higher in rats fed ad libitum than in animals experiencing more than one cycle of 3 days of fasting followed by 3 days of refeeding. Despite the significant body weight reduction, an unusual increase of lipogenesis in WAT was found after multiple cycles of starvation-refeeding of rats on standard laboratory diet. The rate of lipogenesis in the liver and BAT was also elevated but to a much smaller extent. A parallel increase in enzymatic activities related to fatty acid synthesis, ie, fatty acid synthase, acetyl-coenzyme A carboxylase, adenosine triphosphate (ATP)-citrate lyase, NADP-linked malic enzyme, and hexose monophosphate shunt dehydrogenases, suggests that the increased rate of lipogenesis in WAT is a consequence of increased lipogenic enzyme activities. These data suggest that upregulation of WAT lipogenesis occurs after the multiple cycles of the starvation-refeeding protocol. An unusual increase of lipogenesis in rat WAT may have a survival advantage, because starved-refed rats must develop the ability to ingest large amounts of food during a refeeding period to store it in a convenient form than can be used as an oxidizable substrate during a period of starvation. Moreover, these results suggest that it is possible to develop appropriate starvation-refeeding conditions that may inhibit body weight gain.

Adipose Tissue↗
PubMed1997

[Obesity genes].

Explore the source record for details and available documents.

Adipose Tissue↗
PubMed1996

Erythrocyte nucleotides and blood hypoxanthine in patients with uremia evaluated immediately and 24 hours after hemodialysis.

Using high-performance liquid chromatography, concentrations of erythrocyte adenine nucleotides and hypoxanthine were evaluated in patients undergoing regular acetate hemodialysis before dialysis, immediately following dialysis, and 24 hr after. It was shown that adenosine triphosphate concentration was maintained consistently high, not only just after hemodialysis but also 24 hr later. There was also no difference in concentration of mono- and diphosphates of adenosine. Hypoxanthine concentration decreased twofold after hemodialysis. However, it was still markedly higher than normal values. The level of hypoxanthine was maintained at the postdialysis level, 24 hr later. This suggests that hypoxanthine production could be stimulated during acetate dialysis.

Adult↗
PubMed1995

A comparison of the secondary structure of human brain mitochondrial and cytosolic 'malic' enzyme investigated by Fourier-transform infrared spectroscopy.

The secondary structure of human brain cytosolic and mitochondrial 'malic' enzymes purified to homogeneity has been investigated by Fourier-transform IR spectroscopy. The absorbance IR spectra of these two isoenzymes were slightly different, but calculated secondary-structure compositions were essentially similar (38% alpha-helix, 38-39% beta-sheet, 14% beta-turn and 9-10% random structure). These proportions were not affected by succinate, a positive effector of mitochondrial 'malic' enzyme activity. IR spectra indicate that the tertiary structures of human brain cytosolic and mitochondrial 'malic' enzymes are slightly different, and addition of succinate does not cause conformational changes to the tertiary structure of the mitochondrial enzyme. Thermal-denaturation patterns of the cytosolic and mitochondrial enzymes, obtained from spectra recorded at different temperatures in the absence or presence of Mg2+, suggest that the tertiary structure of both isoenzymes is stabilized by bivalent cations and that the cytosolic enzyme possesses a more compact tertiary structure.

Brain↗
PubMed1995

Comparative studies on NADP(+)-linked malic enzyme in the central nervous system of ectothermic and endothermic animals.

The maximum activity and intracellular distribution of NADP(+)-linked malic enzyme in brain of Mammalia, Aves, Reptilia, Amphibia and Pisces are reported. Malic enzyme activity was present in all animals brains investigated. Most of the enzyme activity was located in the mitochondrial fraction. In brain of endothermic animals the activity of malic enzyme was several-fold higher than in ectothermic animals. Other NADPH-producing enzymes (i.e. NADP(+)-linked isocitrate dehydrogenase and hexosemonophosphate shunt dehydrogenase) activities were essentially similar in all animals brains tested. However, the total potential capability of NADPH production was lower in ectothermic animals (due mainly to lower malic enzyme activity). It is suggested that the presence of NADP(+)-linked malic enzyme in the brain may be related mainly to mitochondrial metabolism, especially to maintain the mitochondrial pool of NADP+ in reduced form.

Animals↗
PubMed1995

Purification and properties of cytosolic and mitochondrial malic enzyme isolated from human brain.

Three isoforms of malic enzyme have been described in mammalian tissues: a cytosolic NADP(+)-dependent enzyme, a NADP(+)-dependent mitochondrial isoform and a mitochondrial isozyme which can use both NAD+ and NADP+ but is more effective with NAD+. We purified mitochondrial and cytosolic malic enzyme from human brain extract to apparent homogeneity in order to compare properties of these isozymes and to verify whether mitochondria contain one or two malic enzyme. Specific activities of both isoforms are approx. 90 mumol/min/mg of protein, which corresponds to about 1900-fold purification. The two isozymes have identical native molecular mass (257 kDa) and are presumably tetramers composed of four identical subunits (M(r) = 64 kDa). The isoelectric point of cytosolic isozyme is 5.65, and that of mitochondrial one is 7.0. The isozymes show a substantial difference in their capability to catalyse the reductive carboxylation of pyruvate to malate: the maximal carboxylation rate approaches 80% that of decarboxylation velocity for the cytosolic enzyme, and only 17% for the mitochondrial isozyme. The coenzyme specificity of both isozymes is not stringent; NADP+ is the preferred and NAD+ can substitute it, although with much lower efficiency. The homogenous cytosolic malic enzyme catalysed decarboxylation of oxaloacetate and NADPH-dependent reduction of pyruvate at about 24 and 0.5% of the maximum rate of NADP-dependent oxidative decarboxylation of malate respectively. Decarboxylation of oxaloacetate catalysed by mitochondrial malic enzyme has not been detectable, while NADP-linked reduction of pyruvate approaches only 0.15% of the maximum rate of NADP-linked oxidative decarboxylation of malate.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1995

Different regulatory properties of the cytosolic and mitochondrial forms of malic enzyme isolated from human brain.

The human brain contains a cytosolic and mitochondrial form of NADP(+)-dependent malic enzyme. To investigate their possible metabolic roles we compared the regulatory properties of these two iso-enzymes. The mitochondrial malic enzyme exhibited a sigmoid substrate saturation curve at low malate concentration which was shifted to the right at both higher pH values and in the presence of low concentration of Mn2+ or Mg2+. Succinate or fumarate increased the activity of the mitochondrial malic enzyme at low malate concentration. Both activators shifted the plot of reaction velocity versus malate concentration to the left, and removed sigmoidicity, but the maximum velocity was unaffected. The activation was associated with a decrease in Hill coefficient from 2.3 to 1.1. The human brain cytosolic malic enzyme displayed a hyperbolic substrate saturation kinetics and no sigmoidicity was detected even at high pH and low malate concentrations. Succinate or fumarate exerted no effect on the enzyme activity. Excess of malate inhibited the oxidative decarboxylation catalysed by cytosolic enzyme at pH 7.0 and below. In contrast, decarboxylation catalysed by mitochondrial malic enzyme, was unaffected by the substrate. These results suggest that under in vivo conditions, cytosolic malic enzyme catalyses both oxidative decarboxylation of malate and reductive carboxylation of pyruvate, whereas the role of mitochondrial enzyme is limited to decarboxylation of malate. One may speculate that in vivo the reaction catalysed by cytosolic malic enzyme supplies dicarboxylic acids (anaplerotic function) for the formation of neurotransmitters, while the mitochondrial enzyme regulates the flux rate via Krebs cycle by disposition of the tricarboxylic acid cycle intermediates (cataplerotic function).

Brain↗
PubMed1994

Subregional and intracellular distribution of NADP-linked malic enzyme in human brain.

High total activity (expressed as mumol/min/g of wet tissue or per milligram of DNA) and differential subregional distribution of NADP-linked malic enzyme was found in autopsy specimens of human brain. Striatum showed the highest activity of malic enzyme, which was two- to five-fold higher than that in other human organs tested. High activity was also found in frontal cortex, while the lowest activity of the enzyme in the central nervous system was found in cerebellum, substantia alba, and corpus callosum. In striatum, frontal cortex, pons, and cerebellum more than 80% of total malic enzyme activity was localized in the mitochondrial fraction, while in substantia alba and corpus callosum approximately 60% of the enzyme activity was present in the mitochondrial fraction. Relatively high specific activity of malic enzyme was found in a crude mitochondrial fraction isolated from various regions of human brain. The highest specific activity was found in the mitochondria isolated from striatum (more than 100 nmol/min/mg of mitochondrial protein); the lowest, but still high (approximately 32 nmol/min/mg of mitochondrial protein) was present in corpus callosum. These data and the different ratios of citrate synthase to mitochondrial malic enzyme activities found in different regions of brain suggest that human brain mitochondria, like the mitochondria isolated from other mammalian brains, are extremely heterogenous. A possible role of mitochondrial malic enzyme in human brain metabolism is discussed.

Brain↗
PubMed1993

Phosphate-dependent glutaminase of rat skeletal muscle. Some properties and possible role in glutamine metabolism.

A relatively high activity (26.7 nmol/min per mg mitochondrial protein) of phosphate-dependent glutaminase (EC 3.5.1.2; L-glutamine amidohydrolase) was found in rat skeletal muscle (mixed type from hindlegs) mitochondria incubated in 200 mM potassium phosphate (pH 8.2); the activity was lower in rat heart and diaphragm mitochondria. Phosphate-dependent glutaminase was also found in human skeletal muscle mitochondria, but the activity was about 3-5 times lower than in rat skeletal muscle. Multiplying the specific activity of mitochondrial glutaminase by the amount of mitochondrial protein present in 1 g of rat skeletal muscle the maximum glutaminase activity was found to be 0.352 mumol/min per g wet tissue. The rat skeletal muscle enzyme appears to be similar in many respects to phosphate-dependent glutaminase of the kidney (e.g., S0.5 for glutamine, K0.5 for phosphate, the pH activity profile, inhibition by glutamate). These properties make the skeletal muscle enzyme very similar to the 'kidney type' glutaminase isoenzyme of rat tissues. A significant difference between rat kidney and skeletal muscle enzymes is their adaptive response during acidosis. While the kidney enzyme increases during acidosis, the skeletal muscle glutaminase activity does not. A possible role of glutaminase in the glutamine metabolism in rat skeletal muscle is discussed.

Animals↗
PubMed1993

Acetate-induced changes of adenine nucleotide levels in rat liver.

The changes in adenine nucleotide concentration induced by acetate were investigated in rat liver in situ and in isolated rat hepatocytes. Adenosine monophosphate (AMP) concentration increased approximately threefold within 15 minutes after intraperitoneal injection of sodium acetate. A small but significant decrease in adenosine triphosphate (ATP) concentration also occurred. Consequently, the ATP/AMP ratio decreased from approximately 14 (the value found in control or sodium chloride-injected rats) to approximately 3 (the value found in sodium acetate-injected rats). Adenosine diphosphate (ADP) concentration increased slightly, but this was statistically nonsignificant. Total adenine nucleotide concentrations after acetate injection remained essentially the same as those in control rats. Adenylate energy charge decreased after acetate administration. No significant changes in nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) concentrations were found after sodium acetate injection. Similar patterns of changes in adenine nucleotide concentrations were found in isolated rat hepatocytes incubated in the presence of acetate. These data indicate that acetate, which appears in human blood either during hemodialysis with acetate-containing solution or after ethanol consumption, may alter energy equilibrium of adenine nucleotides in the liver. This is due to the conversion of ATP to AMP in the course of acetate to acetyl-coenzyme A (CoA) activation. It is therefore possible that accelerated ATP turnover in the liver may contribute both to the "intolerance to acetate" in patients subjected to dialysis with the sodium acetate-containing solution and to the pathogenesis of gout associated with excessive ethanol consumption.

Acetates↗
PubMed1993

Changes of nucleotide content in human and rat heart during cardiac surgery and ischemia.

The influence of ischemia on purine nucleotide and their catabolite concentration in human myocardium was investigated during surgery of acquired and congenital heart defects. This was compared with the influence of ischemia on rat heart. Concentrations of adenine and guanine nucleotides and their catabolites were measured in the extracts of heart biopsies taken at the onset of ischemia and at the time of reperfusion. The content of myocardial ATP in human heart decreased from the initial value of 22.3 +/- 1.1 to 14.6 +/- 1.5 nmol/mg protein and total adenine nucleotide pool decreased from 34.2 +/- 1.8 to 27.6 +/- 1.5 nmol/mg protein during the operation. Significant increases in myocardial concentrations of purine catabolites were also observed with the most prominent rise in inosine from below 0.5 at the onset of the ischemia to 3.0 +/- 0.5 nmol/mg protein at the time of reperfusion. A positive correlation was demonstrated between the concentration of purine catabolites in the heart at the end of ischemia with the decrease of both ATP and the total nucleotide pool. An interesting metabolic specificity of the ischemic human heart appeared to be only a small accumulation of inosine monophosphate (IMP). The increase of IMP in the rat heart after ischemia was several-fold higher. Thus, cardiac surgery of congenital and acquired heart defects was associated with a significant decrease in myocardial adenylate pool and a single biopsy collected at the end of ischemia seems to be sufficient to evaluate the extent of this metabolic and possibly functional impairment of the heart.

Adenine Nucleotides↗