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R Scholz

Publications and source records attributed to R Scholz.

At least 73 records · Page 4Linked to original sources
PubMed1984

Influence of fatty acids on energy metabolism. 1. Stimulation of oxygen consumption, ketogenesis and CO2 production following addition of octanoate and oleate in perfused rat liver.

Changes in metabolic rates (oxygen consumption, ketogenesis, 14CO2 production from labelled fatty acids, glycolysis) following the addition of octanoate or oleate were studied in isolated livers from fed and starved rats perfused with Krebs-Henseleit bicarbonate buffer in a non-recirculating system. The following results were obtained. The infusion of fatty acids caused a large increase in the rate of oxygen consumption. The effect was greater with octanoate than with oleate and was half-maximal with fatty acid concentrations (free plus albumin bound) around 0.1 mM. The effects of oleate were only partially suppressed when the perfusate contained albumin concentrations near the physiological range. When fatty acids were oxidized at high rates, the glycolytic rate was diminished by 50%. The increase in oxygen consumption could not be explained fully by the increased ATP demand for fatty acid metabolism or by a compensation for the diminished extramitochondrial ATP generation. In the presence of phenylalkyl oxirane carboxylic acid, an inhibitor of the transport of long-chain acyl-CoA derivates into the mitochondria, ketogenesis and 14CO2 production from labelled oleate were strongly inhibited, whereas the increase in oxygen consumption was only slightly affected. In the presence of antimycin A, the increase in oxygen consumption due to fatty acids was totally abolished. Following pretreatment of rats with ciprofibrate (induction of enzymes for peroxisomal beta-oxidation of long-chain fatty acids), ketogenesis (but not 14CO2 production) from oleate was enhanced threefold. The increase in oxygen consumption, however, was not affected. In conclusion, the increase in hepatic oxygen consumption due to addition of fatty acids reflects a mitochondrial process; it is, in part, independent of the ATP demand of the cell. An uncoupling-like effect of fatty acids on the respiratory chain and its possible physiological significance in ketogenesis are discussed.

Adenosine Triphosphate↗
PubMed1984

Influence of fatty acids on energy metabolism. 2. Kinetics of changes in metabolic rates and changes in subcellular adenine nucleotide contents and pH gradients following addition of octanoate and oleate in perfused rat liver.

The uncoupling-like effect of fatty acids [ Scholz , R., Schwabe , U., and Soboll , S. (1984) Eur. J. Biochem. 141, 223-230] was further substantiated in experiments with perfused rat livers by two ways: firstly the kinetics of changes in metabolic rates (oxygen consumption, ketogenesis, fatty acid oxidation) were analysed; secondly subcellular contents of adenine nucleotides and pH gradients across the mitochondrial membrane were determined following fractionation of freeze-fixed and dried tissues in non-aqueous solvents. The following results were obtained. The relaxation kinetics of the increase in oxygen consumption following fatty acid infusion revealed two components, a rapid one with a half-time around 10 s and a slow one with a half-time of more than 100 s. The rapid component was similar to the kinetics of fatty acid oxidation (ketogenesis and 14CO2 production from labelled fatty acids) whereas the half-time of the slow component was in the range of half-times observed with the increase in oxygen consumption following addition of carbonylcyanide p-trifluoromethoxyphenylhydrazone. In the presence of fatty acids, the cytosolic ATP concentrations and ATP/ADP ratios decreased, whereas the corresponding parameters for the mitochondrial space were either increased (oleate) or decreased (octanoate). The effects of oleate were dependent on the albumin concentrations in the perfusate. The normally large difference between cytosolic and mitochondrial ATP/ADP ratios became smaller. Similar observations were obtained with uncoupling agents. The pH gradient across the mitochondrial membrane as calculated from the subcellular distribution of 5,5 dimethyl[2-14C]oxazolidine-2,4-dione was inversed following the addition of both carbonylcyanide p-trifluoromethoxyphenylhydrazone and fatty acids, i.e. the mitochondrial matrix became more acidic than the cytosol. The pH gradient was not affected when oleate was added in the presence of high albumin concentrations. The data support the hypothesis that the increase in hepatic oxygen consumption due to octanoate or oleate is, in part, caused by a mechanism similar to uncoupling of oxidative phosphorylation. This mechanism seems not to be an artifact of isolated systems; it may be of physiological importance for processes in which reducing equivalents are removed independently of the ATP demand of the hepatocyte.

Adenine Nucleotides↗
PubMed1984

Regulation of oxygen consumption in perfused rat liver: decrease by alpha-sympathetic nerve stimulation and increase by the alpha-agonist phenylephrine.

In livers perfused with Krebs-Henseleit bicarbonate buffer containing bovine red cells, 5 mM glucose and 2 mM lactate, electrical stimulation round the hepatic artery and the portal vein caused via alpha-receptors a decrease in oxygen consumption and portal flow, an increase in glucose output and a switch from lactate uptake to output. In livers perfused with erythrocyte- and substrate-free buffer both in a volume- or pressure-constant system stimulation of the liver nerves resulted in similar changes. Infusion of the alpha-agonist phenylephrine mimicked the metabolic and hemodynamic nerve effects, but led to an increase in oxygen uptake. The converse effects of alpha-sympathetic nerve stimulation and alpha-agonist infusion on oxygen consumption indicate either a different mode of action or a complex mechanism with opposing metabolic and hemodynamic components.

Animals↗
PubMed1984

A crystalline test specimen for checking the performance of high-resolution electron microscopes.

A thin single crystal (001) film of gold with a favourable perforation is described. Examples of its versatile applications to test procedures and calibrations in high-resolution electron microscopy are illustrated. The advantage of such gold films mainly results from the good visibility of dark-field/bright-field image displacements at perforation edges in well defined crystallographic orientations.

Microscopy, Electron↗
PubMed1984

Histoplasma capsulatum in the eye.

The ocular pathologic findings in an immunosuppressed patient who died of disseminated histoplasmosis are described. Histoplasma capsulatum was found in large numbers within the endothelial cells of the choroid, in one area each of the ciliary body and trabecular meshwork. There was a minimal inflammatory response. No granulomas were noted. Previously reported cases of ocular histoplasmosis in immunosuppressed patients are similar in that, with one exception, granulomatous inflammation was not demonstrated. Thirteen eyes in which histoplasma organisms have been found in the eye are reviewed.

Adult↗
PubMed1983

Actions of glucagon on flux rates in perfused rat liver. 1. Kinetics of the inhibitory effect on glycolysis and the stimulatory effect on glycogenolysis.

Changes in the rates of glucose, lactate and pyruvate production following infusion of glucagon were studied in isolated livers from fed or fasted rats perfused with non-recirculating Krebs-Henseleit bicarbonate buffer. Evidence was presented that under these experimental conditions, the release of lactate plus pyruvate into the perfusate represents 80-90% of the total glycolytic flux; oxidation of pyruvate derived from glucose and/or glycogen accounts for the remaining 10-20%, whereas recycling of pyruvate to glucose is negligible. In the presence of glucagon, rates of lactate plus pyruvate production were diminished to less than 30% in the fed state (glycogen as substrate) and to less than 10% in the fasted state (glucose as substrate). Rates of pyruvate oxidation were unchanged. Although recycling of pyruvate to glucose was enhanced, it could account for not more than 20% of the decrease in lactate plus pyruvate production. The data indicate a strong inhibition of the substrate flux through glycolysis. The glucagon concentration for half-maximal inhibition of glycolysis was 0.2 nM, independent of the substrate (glucose or glycogen) and the nutritional state. The effective concentrations were within the physiological range of glucagon concentrations reported for portal venous blood. Transient state analyses indicated that the inhibition of glycolysis precedes the stimulation of glycogenolysis. When after a delay glycogenolysis was accelerated, it was followed by a transient stimulation of glycolysis. The stimulatory component in the glucagon effect on glycolysis was diminished in glycogen-depleted livers and when glucose was the main substrate. The coordinated control of glycolysis and glycogenolysis by glucagon and the interaction of the two processes in the transient state are discussed.

Animals↗
PubMed1983

Actions of glucagon on flux rates in perfused rat liver. 2. Relationship between inhibition of glycolysis and stimulation of respiration by glucagon.

The relationship between inhibition of glycolysis and stimulation of oxygen consumption by glucagon was studied in perfused rat livers. The two effects exhibit similar kinetics and dose-response curves; they are slower and less sensitive to the glucagon concentration than the stimulatory effect on glycogenolysis. A stoichiometry of 1 mol extra oxygen consumed/1.8 mol of diminished lactate plus pyruvate production was found. Under conditions where glucagon did not cause a marked inhibition of glycolysis (i.e. low glycolytic flux rates in the fasted state or in the presence of ethanol), oxygen consumption was also not markedly increased. These findings provide evidence that the major portion of glucagon-induced stimulation of hepatic respiration in the fed state is due to an enhanced demand for mitochondrial oxidative phosphorylation to compensate for the diminished extramitochondrial ATP production following inhibition of glycolysis by glucagon.

Animals↗
PubMed1982

Role of pyruvate transporter in the regulation of the pyruvate dehydrogenase multienzyme complex in perfused rat liver.

Metabolic substrates such as octanoate, beta-hydroxybutyrate, and alpha-ketoisocaproate which produce acetoacetate stimulate the rate of pyruvate decarboxylation in perfused livers from fed rats at perfusate pyruvate concentrations in the physiological range (below 0.2 mM). A quantitative relationship between pyruvate oxidation (14CO2 production from [1-14C]pyruvate) and ketogenesis (production of acetoacetate or total ketone bodies) was observed with all ketogenic substrates when studied over a wide range of concentrations. The ratio of extra pyruvate decarboxylated to extra acetoacetate produced was greater than 1 with octanoate and alpha-ketoisocaproate, but it was less than 1 with beta-hydroxybutyrate. The stimulatory effect of beta-hydroxybutyrate on pyruvate decarboxylation was abolished completely in the presence of 0.1 mM alpha-cyanocinnamate, an inhibitor of the pyruvate transporting system in the mitochondrial membrane. The data suggest that the mechanism by which the flux through the pyruvate dehydrogenase reaction is stimulated in liver under ketogenic conditions involves an acceleration of the net rate of pyruvate transport into the mitochondria compartment due to an exchange with acetoacetate and/or acetoacetate plus beta-hydroxybutyrate.

Acetoacetates↗
PubMed1982

Effects of genetic resistance against Herpes simplex virus in vaginally infected mice.

In order to take the conditions of natural Herpes simplex virus (HSV) infection into consideration, the genetic resistance of C57-Bl mice, which was established by intraperitoneal HSV-1 infection [Lopez, 1975], was investigated in vaginally infected mice. The course of infection in the mucous membranes did not differ in sensitive (NMRI) and resistant (C57-Bl) mice: both number of takes and virus elimination from the vagina were equal, and no difference in viral titer produced in the vagina was detected. Viral titer in the productively infected lumbosacral ganglia, however, was less in the resistant mice. An experiment with foot-pad-infected mice confirmed that the number of productively infected ganglia was reduced in resistant mice, and contralateral ganglia were infected only in the sensitive mouse strain. In spite of this, the number of latently infected animals did not vary significantly in the mouse strains. Higher activity of defense mechanisms in resistant mice, apparently localized in the ganglia, resulted in reduced lethality. As to the mechanisms of the resistance, neither antibody nor interferon response were enhanced in C57-Bl mice, but resistance was abolished by depletion of several cellular functions, i.e., lymphocytes by cyclophosphamide or X-rays, macrophages by silica or macrophage-antiserum, and M-cells by 89Sr.

Animals↗
PubMed1982

Rates of flux through the pentose cycle in perfused rat liver. A procedure for the calculation of rates of substrate flux from 14CO2 production from [1-14C]glucose.

A method for the determination of substrate flux through the pentose cycle was developed employing [1-14C]glucose in experiments with perfused rat livers. The method consists first of a kinetic analysis which differentiates between the production of 14CO2 from [1-14C]glucose via the pentose cycle and via the citrate cycle and, second of a calculation of the specific radioactivity of the hexose monophosphate pool from measured rates of glycolysis and the specific radioactivity of lactate released into the perfusate. The method was validated by experiments comparing the results of tracer infusions with [1-14C]glucose, [6-14C]glucose and [3-14C]pyruvate. In livers from fed rats perfused with 10 mM glucose, the rate of substrate flux through the pentose cycle was around 0.2 mumol X min-1 X g-1; it was about 20% of the substrate flux via glycolysis. The kinetic data were inconsistent with the existence of an L-type pentose cycle in liver.

Animals↗
PubMed1981

Transport of inorganic anions in perfused rat liver.

The transport of inorganic anions (sulfate, chloride, phosphate and bicarbonate) across the plasma membrane was investigated in hemoglobin-free perfused rat livers, applying the multiple-indicator dilution technique (pulse labelling of inorganic anions and indicator substances). The following results were obtained: 1. Chloride and phosphate exchanged very slowly between extracellular and intracellular spaces, whereas the exchange of sulfate was rapid. 2. The exchange of sulfate exhibited saturation kinetics with half-maximal rates at approximately 8mM sulfate. The maximal steady-state exchange rate was near 60 micromol x min-1 x (g liver wet wt)-1. 3. The exchange of sulfate was inhibited completely by cyanocinnamate; the inhibition was fully reversible. It was also completely, but irreversibly inhibited by diisothiocyanostilbenedisulfonic acid; the amount of the inhibitor bound by the liver that was required for half-maximal effect was considerably less than that required for the inhibition of D-lactate transport. 4. The exchange of sulfate was also inhibited by pyruvate and L-lactate at high concentrations; the inhibition was not competitive. 5. The exchange of D-lactate was not inhibited by sulfate or chloride. 6. Bicarbonate exchanges very rapidly; this process cannot be inhibited by cyanocinnamate. From these observations the following conclusions were drawn. A carrier system for the transport of inorganic anions, at least for sulfate, exists in the plasma membrane of liver. This carrier is specific for inorganic anions and is independent of the carrier system for the transport of monocarboxylates, in contrast to the findings with erythrocytes. Moreover, this carrier does not transport bicarbonate at a significant rate. Most likely, the rapid exchange of bicarbonate reflects the free diffusion of carbon dioxide.

Animals↗
PubMed1981

Changes in the subcellular distribution of metabolites due to ethanol oxidation in the perfused rat liver.

The subcellular distribution of metabolites involved in the transfer of reducing equivalents across the mitochondrial membrane was studied in perfused livers from fed rats. A tenfold increase in the flux rate of the malate-aspartate shuttle and the inhibition of the citrate cycle due to ethanol oxidation, were reflected by characteristic changes in the cytosolic and mitochondrial concentrations of malate, 2-oxoglutarate, aspartate, glutamate and citrate. The data suggest that the malate-aspartate shuttle is triggered by a decrease in the cytosolic oxaloacetate concentration which, due to the cytosolic aspartate aminotransferase equilibrium, leads to an increased efflux of 2-oxoglutarate and aspartate from the mitochondria in exchange for malate and glutamate, respectively. The first site at which the citrate cycle is inhibited appears to be the level of 2-oxoglutarate oxidation.

Animals↗
PubMed1980

Metabolic changes after prior treatment with ethanol. Evidence against in involvement of the Na+ + K+-activated ATPase in the increase in ethanol metabolism.

In perfused rat liver, the inhibition of ethanol uptake by ouabain does not follow the rapid inhibition of the Na+ K+- activated ATPase as assessed by changes in perfusate [K+] (half-time, t 1/2 = 2--3 min), but correlated rather with the slow inhibition of oxygen uptake (maximal inhibition = 40% in 20 min). The data indicate that ouabain exerts its effect on ethanol metabolism via the following sequence of events; inhibition of the sodium pump is followed gradually by a perturbation of the intracellular cation milieu; this leads to an inhibition of the mitochondrial respiratory chain, resulting in diminished rate of NADH oxidation, which in turn causes in inhibition of ethanol metabolism.

Animals↗