Metabolism of R- and S-1,3-butanediol in perfused livers from meal-fed and starved rats.
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ABSTRACT:
SUBMITTER: Desrochers S
PROVIDER: S-EPMC1132838 | biostudies-other | 1992 Jul
REPOSITORIES: biostudies-other
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Project description:Liver content of pentose-cycle intermediates and the activity of the three major cytoplasmic NADPH-producing enzymes and pentose-cycle enzymes were measured in three dietary states: 48 h-starved rats, rats fed on a standard diet ad libitum, and rats meal-fed with a low-fat high-carbohydrate diet. Measured tissue contents of pentose-cycle intermediates in starved liver were: 6-phosphogluconate, 4.7 +/- 0.5 nmol/g; ribulose 5-P, 3.7 +/- 0.5 nmol/g; xylulose 5-P, 4.3 +/- 0.4 nmol/g; sedoheptulose 7-P, 25.5 +/- 1.3 nmol/g; and combined sedoheptulose 7-P and ribose 5-P, 30.6 +/- 0.7 nmol/g. These values were in good agreement with values calculated from fructose 6-P and free glyceraldehyde 3-P, assuming the major transketolase, transaldolase, ribulose-5-P 3-epimerase and ribose-5-P isomerase reactions were all in near-equilibrium. Similar results were found in animals fed ad libitum. These relationships were not valid in animals fed on a low-fat high-carbohydrate diet, with tissue contents of metabolites in some cases being more than an order of magnitude higher than the calculated values. Measured tissue contents of pentose-cycle intermediates in these animals were: 6-phosphogluconate, 124.2 +/- 13.9 nmol/g; ribulose 5-P, 44.8 +/- 7.1 nmol/g; xylulose 5-P, 77.2 +/- 9.4 nmol/g; sedoheptulose 7-P, 129.9 +/- 10.1 nmol/g; and combined sedoheptulose 7-P and ribose 5-P, 157.0 +/- 11.3 nmol/g. In all animals, regardless of dietary state, tissue content of erythrose 4-P was less than 2 nmol/ml. Liver activities of glucose-6-P dehydrogenase and 6-phosphogluconate dehydrogenase were increased from 3.5 +/- 0.9 mumol/g and 7.3 +/- 0.5 mumol/min per g in starved animals to 13.2 +/- 1.1 and 10.5 +/- 0.7 mumol/min per g in low-fat high-carbohydrate-fed animals. Despite these changes, the activities of transaldolase (3.4 +/- 0.3 mumol/min per g), transketolase (7.8 +/- 0.2 mumol/min per g) and ribulose-5-P 3-epimerase (7.5 +/- 0.4 mumol/min per g) were not increased in meal-fed animals above those observed in starved animals (3.4 +/- 0.2, 7.1 +/- 0.3 and 8.6 +/- 0.4 mumol/min per g respectively). The increase in the activity of oxidative pentose-cycle enzymes in the absence of any change in the non-oxidative pentose cycle appeared to contribute to the observed disequilibrium in the pentose cycle in animals meal fed on a low-fat high-carbohydrate diet.
| S-EPMC1146893 | biostudies-other
Project description:Acetoacetate was the sole ketone body formed when livers from starved rats were perfused with minimal concentrations of non-esterified fatty acid. Absence of 3-hydroxybutyrate was related to a low substrate potential, which caused a more oxidized redox state and a decreased [ATP]/[ADP] ratio. Only under conditions of comparable non-esterified fatty acid uptake was lipoprotein triacylglycerol production inversely related to ketogenesis.
| S-EPMC1158602 | biostudies-other
Project description:1. Rats were starved for 48hr. or fed for 1 week on a high-fat or a high-carbohydrate diet. The effects of these dietary alterations on the rate of production of (14)CO(2) from trace amounts of [U-(14)C]glucose, [1-(14)C]palmitate or [1-(14)C]acetate administered intravenously were studied. 2. The oxidation of [(14)C]glucose was most rapid in the carbohydrate-fed condition and was decreased significantly and to the same extent after starvation and after feeding with fat. 3. Under all dietary regimes studied the maximum rate of elimination of (14)CO(2) from [(14)C]palmitate occurred within a few minutes after injection, but considerably more was oxidized after starvation and feeding with fat than after feeding with carbohydrate. 4. Alterations in diet had no effect on the oxidation and high recovery of administered [(14)C]acetate as (14)CO(2). 5. Graphical analysis showed the presence of several exponential components in the (14)CO(2)-elimination curves. 6. In all studies a marked similarity in oxidative pattern was noted between the starved and the fat-fed rat.
| S-EPMC1270421 | biostudies-other
Project description:1. The influence of ethanol on the metabolism of livers from fed and starved rats has been studied in liver-perfusion experiments. Results have been obtained on oxygen consumption and carbon dioxide production, on glucose release and uptake by the liver and on changes in the concentrations of lactate and pyruvate and of beta-hydroxybutyrate and acetoacetate in the perfusion medium. 2. Oxygen consumption and carbon dioxide production were lower in livers from starved rats than in livers from fed rats. Ethanol had no effect on the oxygen consumption of either type of liver. After the addition of ethanol to the perfusion medium carbon dioxide production ceased almost completely, the change being faster in livers from starved rats. 3. With livers from fed rats glucose was released from the liver into the perfusion medium. This release was slightly greater when ethanol was present. With livers from starved rats no release of glucose was observed, and when ethanol was added a marked uptake of glucose from the medium was found. A simultaneous release of glycolytic end products, lactate and pyruvate, into the medium occurred. 4. Acetate was the main metabolite accumulating in the perfusion medium when ethanol was oxidized. With livers from starved rats a slightly increased formation of ketone bodies was found when ethanol was present. 5. The lactate/pyruvate concentration ratio in the perfusion medium increased from 10 to 87 with livers from fed rats and from 20 to 171 with livers from starved rats when the livers were perfused with ethanol in the medium. The beta-hydroxybutyrate/acetoacetate concentration ratio increased from 0.8 to 7.6 with livers from fed rats and from 1.0 to 9.5 with livers from starved rats when ethanol was added to the medium. 6. The effects of ethanol are discussed and related to changes in the redox state of the liver that produce new conditions for some metabolic pathways.
| S-EPMC1206436 | biostudies-other
Project description:1. Rats were treated for 4 weeks with liquid diets that contained, on the basis of energy content, 35% fat, 18% protein and 47% carbohydrate (high-fat diet) or 35% fat, 18% protein, 11% carbohydrate and 36% ethanol (high-fat/ethanol diet). 2. The livers were perfused with 1mm-[1-(14)C]palmitate and with 0, 10mm- or 80mm-ethanol. The oxidation and esterification of palmitate was measured. Two subcellular pools of triacylglycerol were separated; one contained triacylglycerol from cytoplasmic lipid droplets and the other contained triacylglycerol from the endoplasmic reticulum and Golgi apparatus. 3. In the presence of ethanol, liver from rats fed on the high-fat diet esterified about 70% of the [1-(14)C]palmitate taken up compared with 90% in liver from rats fed chow (containing 11% fat on the basis of energy content). Compared with chow diet the high-fat diet did not potentiate the effect of ethanol on storage of [1-(14)C]palmitate in hepatic triacylglycerol. The relation between the fat content of the diet and the degree of fatty liver induced by by ethanol [Lieber & DeCarli (1970) Am. J. Clin. Nutr.23, 474-478] is discussed. 4. The ethanol-containing diet increased the hepatic content of triacylglycerol 4-fold and the increase was exclusively found in the fraction suggested to contain lipid from cytoplasmic lipid droplets. The ethanol-induced fatty liver, perfused with ethanol, esterified and oxidized palmitate at rates that were quite similar to the rates found in high-fat control livers perfused without ethanol. This suggests that the fatty liver had adapted to the presence of ethanol with respect to palmitate metabolism. 5. O(2) and ethanol uptake by the livers were not affected by the ethanol-containing diet.
| S-EPMC1161678 | biostudies-other
Project description:Meal-fed rats and rats fed ad libitum had similar rates of hepatic glycogenesis at 60 min after the initiation of re-feeding a chow meal after 22 h starvation, but hepatic PDHa (active form of pyruvate dehydrogenase) activities were 4-fold higher in the meal-fed group. In heart, PDHa activities were 3-fold higher before re-feeding and 2-fold higher after re-feeding in the meal-fed group compared with the group fed ad lib. The blood metabolite profile suggested diminished fat oxidation in starved meal-fed rats and accelerated flux through PDH in meal-fed re-fed rats compared with the group fed ad lib.
| S-EPMC1133263 | biostudies-other
Project description:1. Mitochondria isolated from livers of fed adult, starved adult, and embryonic rats can be separated into three distinct bands by isopycnic density centrifugation on a sucrose density gradient. The least dense band (B1) has a mean buoyant density of 1.162 and consists mainly of disrupted mitochondria. The middle band (B2) has a mean buoyant density of 1.184. The most dense band (B3) has a mean buoyant density of 1.216. B2 and B3 consist of intact mitochondria. 2. The mitochondria in B2 and B3 have very similar protein/phospholipid ratios, virtually identical phospholipid and fatty acid compositions and similar specific activities for cytochrome oxidase, malate dehydrogenase and monoamine oxidase. Both fractions have very low glucose 6-phosphatase and acid phosphatase activities. 3. As isolated, adult rat liver mitochondria have electron-dense matrices (condensed forms); some embryonic liver mitochondria are condensed, but a significant proportion have dilated matrices. All B2 mitochondria are in the condensed form. B3 mitochondria from adult rats are condensed if fixed in their equilibrium-density sucrose, but when this is diluted rapidly to 0.25m they become swollen. Some B3 mitochondria from embryonic rats are condensed, the others have dilated matrices. They all swell if rapidly diluted to 0.25m-sucrose. B2 mitochondria retain their condensed form on dilution of the sucrose. 4. It is concluded that the matrix space of B2 mitochondria is almost totally inaccessible to sucrose, but that of B3 mitochondria is readily accessible to sucrose. 5. In liver from normally fed adult rats the B2 mitochondria predominate, whereas in starved rats B2 and B3 are present in approximately equal proportions. Mitochondrial preparations from embryonic liver consist predominantly of B3 mitochondria, but the proportion of these decreases progressively as development proceeds. 6. The B2 mitochondria from livers of fed adult rats can be converted into B3 mitochondria by incubation with 10mm-succinate and 10mm-phosphate. 7. Some B2 mitochondria are converted into B3 mitochondria by exposure to high concentrations of sucrose.
| S-EPMC1179050 | biostudies-other
Project description:Isolated liver perfusion systems have been used to characterize intrinsic metabolic changes in liver as a result of various perturbations, including systemic injury, hepatotoxin exposure, and warm ischemia. Most of these studies were done using hyperoxic conditions (95% O(2)) but without the use of oxygen carriers in the perfusate. Prior literature data do not clearly establish the impact of oxygenation, and in particular that of adding oxygen carriers to the perfusate, on the metabolic functions of the liver. Therefore, herein the effects of oxygen delivery in the perfusion system on liver metabolism were investigated by comparing three modes of oxygenation. Rat livers were perfused via the portal and hepatic veins at a constant flow rate of 3 mL/min/g liver in a recirculating perfusion system. In the first group, the perfusate was equilibrated in a membrane oxygenator with room air (21% O(2)) before entering the liver. In the second group, the perfusate was equilibrated with a 95% O(2)/5% CO(2) gas mixture. In the third group, the perfusate was supplemented with washed bovine red blood cells (RBCs) at 10% hematocrit and also equilibrated with the 95% O(2)/5% CO(2) gas mixture. Oxygen and CO(2) gradients across the liver were measured periodically with a blood gas analyzer. The rate of change in the concentration of major metabolites in the perfusate was measured over time. Net extracellular fluxes were calculated from these measurements and applied to a stoichiometric-based optimization problem to determine the intracellular fluxes and active pathways in the perfused livers. Livers perfused with RBCs consumed oxygen at twice the rate observed using hyperoxic (95% O(2)) perfusate without RBCs, and also produced more urea and ketone bodies. At the flow rate used, the oxygen supply in perfusate without RBCs was just sufficient to meet the average oxygen demand of the liver but would be insufficient if it increased above baseline, as is often the case in response to environmental perturbations. Metabolic pathway analysis suggests that significant anaerobic glycolysis occurred in the absence of RBCs even using hyperoxic perfusate. Conversely, when RBCs were used, glucose production from lactate and glutamate, as well as pathways related to energy metabolism were upregulated. RBCs also reversed an increase in PPP fluxes induced by the use of hyperoxic perfusate alone. In conclusion, the use of oxygen carriers is required to investigate the effect of various perturbations on liver metabolism.
| S-EPMC3193557 | biostudies-literature
Project description:A model has been developed to measure the effects of dietary protein on daily fluctuations in the rate of endogenous amino acid oxidation in meal-fed and starved rats. In addition, N tau-methylhistidine and hydroxyproline were utilized to determine changes in the rate of degradation of myofibrillar and collagen proteins. In rats meal-fed a normal diet of 18% (w/w) casein, a diurnal response was observed in rate of oxidation of radioactive amino acids contained in endogenous labelled body protein, with a nadir 16--20 h and maximum 4--8 h after beginning the feeding. This observation in part may be related to alterations in flux of amino acids from non-hepatic tissues to site of oxidation in liver, as well as alterations in rates of amino acid oxidation after a protein meal. When meal-fed a 70% protein diet, the maximal rates of endogenous amino acid oxidation were significantly increased by 4--8 h after meal-feeding, with no change in fractional rates of degradation of myofibrillar- or collagen-protein breakdown. This could suggest increases in activities of enzymes involved in amino acid oxidation, in rats meal-fed 70% compared with 18% dietary protein. In contrast, meal-feeding of a protein-free diet muted the diurnal response in the rate of oxidation of endogenously labelled amino acids, which correlated with a decrease in the fractional rate of degradation of myofibrillar or collagen protein. Thus dietary protein is apparently responsible for the observed diurnal rhythm rhythms in the rate of amino acid oxidation, whereas carbohydrates tend to mute the response.
| S-EPMC1162145 | biostudies-other
Project description:1. To investigate the role of ribosome function in regulating protein synthesis, the activity, distribution and functional states of ribosomal particles were investigated in livers of mice fed ad libitum or starved overnight. 2. The distribution of protein-synthesizing activity between polyribosomes of different sizes was analysed after incorporation of radioactive leucine, and the quantitative distribution of ribosomes as native subunits, monomers and polyribosomes was analysed after incorporation of orotic acid. Precursors labelled with (3)H or (14)C were given separately to fed and starved mice, so that livers from the two groups of animals were processed together. 3. The former experiments showed that starvation has little effect on the distribution of protein-synthesizing activity across polyribosome sedimentation patterns, though the latter experiments showed that the proportion of ribosomes existing as monomers increased from 9.5% to 15.2%, whereas the proportion existing as polyribosomes decreased from 81.4% to 75.6%. Starvation had a negligible effect on the proportion of native subunits, which accounted for 9.1% and 9.2% of the ribosomes in fed and starved mice respectively. 4. The monomeric ribosome fraction was isolated and subjected to ionic conditions which selectively dissociate single ribosomes. Starvation increased the proportion of monomers that dissociated from 59% to 72%, so the monomers that accumulate in livers of starved animals are single ribosomes and not monoribosomes resulting from degradation of polyribosomes. 5. The fate of newly formed ribosomal particles was studied by measuring the specific radioactivity of native subunits, monomers and polyribosomes at different times after injection of radioactively labelled orotic acid. Starvation did not appear to affect equilibration between newly formed particles and polyribosomes, and the radioactivity of polyribosomes in both groups of mice reached about 90% of that in native subunits after 4h. The radioactive labelling of monomers proceeded at a slower rate, especially after starvation. At 4h, the radioactivity of monomers was 64% and 55% that of native subunits in fed and starved mice respectively.
| S-EPMC1177823 | biostudies-other