scholarly journals The effect of propionate on the metabolism of pyruvate and lactate in the perfused rat liver

1972 ◽  
Vol 127 (3) ◽  
pp. 539-543 ◽  
Author(s):  
T. M. Chan ◽  
R. A. Freedland

1. Rates of gluconeogenesis in the perfused rat liver from propionate, l-lactate, pyruvate and the combination of propionate with either lactate or pyruvate were measured. Less than additive rates were obtained with either propionate plus lactate or propionate plus pyruvate. 2. The uptake of pyruvate plus lactate from the perfusion medium was decreased more seriously when propionate was present with lactate than with pyruvate. 3. The use of [2-14C]pyruvate in the presence of propionate showed that the decreased disappearance of pyruvate plus lactate did not result in their formation from propionate. 4. The addition of sodium butyrate to the perfusion medium caused an inhibition of gluconeogenesis from propionate and stimulated gluconeogenesis and uptake of pyruvate and lactate. 5. The observations are consistent with there being a sparing effect of propionate on lactate and pyruvate metabolism.

1967 ◽  
Vol 102 (3) ◽  
pp. 942-951 ◽  
Author(s):  
B. D. Ross ◽  
R. Hems ◽  
H. A Krebs

1. The rates of gluconeogenesis from many precursors have been measured in the perfused rat liver and, for comparison, in rat liver slices. All livers were from rats starved for 48hr. Under optimum conditions the rates in perfused liver were three to five times those found under optimum conditions in slices. 2. Rapid gluconeogenesis (rates of above 0.5mumole/g./min.) were found with lactate, pyruvate, alanine, serine, proline, fructose, dihydroxyacetone, sorbitol, xylitol. Unexpectedly other amino acids, notably glutamate and aspartate, and the intermediates of the tricarboxylic acid cycle (with the exception of oxaloacetate), reacted very slowly and were not readily removed from the perfusion medium, presumably because of permeability barriers which prevent the passage of highly charged negative ions. Glutamine and asparagine formed glucose more readily than the corresponding amino acids. 3. Glucagon increased the rate of gluconeogenesis from lactate and pyruvate but not from any other precursor tested. This occurred when the liver was virtually completely depleted of glycogen. Two sites of action of glucagon must therefore be postulated: one concerned with mobilization of liver glycogen, the other with the promotion of gluconeogenesis. Sliced liver did not respond to glucagon. 4. Pyruvate and oxaloacetate formed substantial quantities of lactate on perfusion, which indicates that the reducing power provided in the cytoplasm was in excess of the needs of gluconeogenesis. 5. Values for the content of intermediary metabolites of gluconeogenesis in the perfused liver are reported. The values for most intermediates rose on addition of lactate. 6. The rates of gluconeogenesis from lactate and pyruvate were not affected by wide variations of the lactate/pyruvate ratio in the perfusion medium.


1978 ◽  
Vol 176 (3) ◽  
pp. 959-965 ◽  
Author(s):  
Gerard J. Mulder ◽  
Katja Keulemans

1. The metabolism of inorganic [35S]sulphate (Na235SO4) was studied in the isolated perfused rat liver at three initial concentrations of inorganic sulphate in the perfusion medium (0, 0.65 and 1.30mm), in relation to sulphation and glucuronidation of a phenolic drug, harmol (7-hydroxy-1-methyl-9H-pyrido[3,4-b]indole). 2. [35S]Sulphate rapidly equilibrated with endogenous sulphate in the liver. It was excreted in bile and reached, at the lowest concentration in the perfusion medium, concentrations in bile that were much higher than those in the perfusion medium; at the higher sulphate concentrations, these concentrations were equal. The physiological concentration of inorganic sulphate in the liver, available for sulphation of drugs, is similar to the plasma concentration. 3. At zero initial inorganic sulphate in the perfusion medium, the rate of sulphation was very low and harmol was mainly glucuronidated. At 0.65mm-sulphate glucuronidation was much decreased and considerable sulphation took place, indicating efficient competition of conjugation by sulphation. At 1.30mm-sulphate the sulphation increased still further. 4. The results suggest that an important factor in sulphation is the relatively high Km of synthesis of adenosine 3′-phosphate 5′-sulphatophosphate (the co-substrate of sulphation) for inorganic sulphate, which is of the order of the plasma concentration of inorganic sulphate. The steady-state adenosine 3′-phosphate 5′-sulphatophosphate concentration may determine the rate of sulphate conjugation of drugs in the rat in vivo.


1973 ◽  
Vol 132 (1) ◽  
pp. 55-60 ◽  
Author(s):  
H. F. Woods ◽  
H. A. Krebs

1. The changes in the metabolite content in the isolated perfused rat liver and in the perfusion medium were measured after loading the liver with glycerol or dihydroxyacetone. 2. Glycerol was rapidly taken up by livers from fed and starved rats; glucose, lactate and pyruvate were discharged into the medium. The [lactate]/[pyruvate] ratio in the medium rose from 10 to 30 and in the tissue from 9.6 to 36.6. 3. The most striking effects of glycerol loading were: (i) the accumulation in the liver of α-glycerophosphate, which increased from 0.13 to 8.45μmol/g at 40min; (ii) the decrease in the concentration of adenine nucleotides to 70% of the control value at 40min. 4. The Pi content of the tissue also fell, from 4.25 to 2.31μmol/g at 10min, but the sum of the phosphates measured rose from the normal value of 13.8 to 18.8μmol/g at 40min, because of an uptake of Pi from the medium. 5. Omission of phosphate from the standard perfusion medium increased the depletion of adenine nucleotides on glycerol loading. 6. Dihydroxyacetone was more rapidly metabolized than glycerol. Again glucose, lactate and pyruvate were the main products. The [lactate]/[pyruvate] ratio remained below 10. 7. Dihydroxyacetone caused an increase of the fructose 1-phosphate content from 0.23 to 0.39μmol/g at 10min. The adenine nucleotide content of the tissue was not significantly decreased by dihydroxyacetone loading. 8. The rate of removal of both glycerol and dihydroxyacetone was about 60% greater in the livers from fed than in those from starved animals. 9. The results extend previous findings by Burch et al. (1970), who administered glycerol and dihydroxyacetone intraperitoneally.


1973 ◽  
Vol 51 (6) ◽  
pp. 418-423 ◽  
Author(s):  
I. M. Yousef ◽  
R. Magnusson ◽  
V. M. Price ◽  
M. M. Fisher

The hepatic metabolism of chenodeoxycholic acid (CDCA) was studied using the isolated perfused rat liver technique. In 12 perfusions, six male and six female, 30 μmol of CDCA were added to the perfusion medium, and in 12 other perfusions, also six of each sex, 1 μmol of CDCA was added to the perfusion medium. The CDCA was added after 2 h of base-line perfusion and the bile acids of liver, plasma, and bile were analyzed by combined thin-layer and gas chromatography. In the 2 h of perfusion prior to the addition of exogenous CDCA there were sex differences in the kinetics of bile acid secretion in the bile and in the bile acid composition of that bile. Following the addition of CDCA to the perfusion medium the female liver was found to take up more CDCA from the perfusion medium, to store more CDCA, and to convert less CDCA to β-muricholic acid. It was documented that the toxicity of CDCA for the isolated perfused liver of the female rat is not due to α- or β-muricholic acid, the end products of CDCA metabolism in the rat. The relatively greater capacity of the male liver to convert potentially toxic CDCA to nontoxic β-muricholic acid may explain, at least in part, the observed sex difference in CDCA hepatotoxicity.


1979 ◽  
Vol 236 (3) ◽  
pp. C139-C143 ◽  
Author(s):  
B. S. Kingsley ◽  
J. M. Frazier

The hypothesis that one component of cadmium uptake by rat hepatocytes involves a mediated transport pathway normally operative for zinc transport was tested in the isolated perfused rat liver preparation. Excess zinc in the perfusion medium suppressed cadmium uptake as indicated by the decrease in the normalized clearance (initial clearance divided by liver weight) from 0.340 +/- 0.019 (ml/min)/g in the presence of normal zinc concentrations (Zn:Cd molar ratio, 1.6) to 0.138 +/- 0.017 (ml/min)/g (Zn:Cd molar ratio, 13.0). In excess-zinc control experiments (no cadmium present) little zinc is accumulated by the liver, apparently due to competition between intrahepatic and extracellular binding. Exposure to cadmium increases both zinc secretion into the perfusion medium and biliary excretion of zinc. The effect at the sinusoidal membrane is probably a result of both the blockage of zinc resorption during cadmium uptake and the displacement of intrahepatic zinc. The effect on biliary excretion of zinc is due solely to displacement of intrahepatic zinc. These results are consistent with the proposed hypothesis for cadmium transport.


1977 ◽  
Vol 75 (1) ◽  
pp. 137-143 ◽  
Author(s):  
D. J. HILL ◽  
M. J. O. FRANCIS ◽  
R. D. G. MILNER

Rat prolactin at a concentration of 50 ng/ml perfusion medium stimulated the production of somatomedin-like activity (SLA) from the perfused liver of normal rats. The effect was demonstrable in perfusions performed at 11.00 h in which rat prolactin caused a mean (±s.e.m.) increase in the uptake of [35S]sulphate into rat costal cartilage in vitro of 64 ± 14% in comparison with controls, but at 15.00 h no effect was observed. No effect of rat prolactin on hypophysectomized rat liver was detectable at 11.00 h. Hypophysectomized and sham-operated rats were given five intravenous injections of 50 μg rat prolactin or a similar volume of hormone solvent at 12 h intervals. Plasma somatomedin activity (SMA) and cartilage metabolism, measured by the uptake of radioactive sulphate and thymidine by costal cartilage in vitro, were similar in hypophysectomized animals given rat prolactin or hormone solvent. Sham-operated rats given rat prolactin showed a significant increase of plasma SMA and cartilage metabolism compared with control animals. The production of SLA by rat liver in response to rat prolactin may be related to the density of specific hepatic lactogenic receptors, since these are absent or present only in low numbers in hypophysectomized animals.


1994 ◽  
Vol 72 (1-2) ◽  
pp. 8-11 ◽  
Author(s):  
H. S. Brand ◽  
A. J. Meijer ◽  
L. A. Gustafson ◽  
G. G. A. Jörning ◽  
A. C. J. Leegwater ◽  
...  

Astrocytes and lymphocytes are able to release significant amounts of taurine during periods of hypotonicity to reduce the increase in cell volume. To investigate this mechanism in the liver, we studied the release of free amino acids from isolated perfused rat liver during hypotonicity. The osmolarity of the perfusion medium was reduced from 305 to 255 or 205 mosM by decreasing the NaCl concentration 25 or 50 mM, respectively. This induced an 6–8% increase in liver mass and was associated with a specific 1.7-fold (−50 mosM) and 14-fold (−100 mosM) increase of the taurine release. None of the other amino acids measured showed a significant increase in their concentration in the effluent. The increase in taurine release occurred within 30 s after exposure to hypotonicity (maximal after 1–1.5 min) and followed closely the changes in liver mass. The taurine release declined gradually during successive exposures of the isolated liver to −100 mosM. This release was 29 and 17% of the original during the second and third exposure, respectively.Key words: cell swelling, liver, taurine.


1982 ◽  
Vol 100 (2) ◽  
pp. 274-278
Author(s):  
M. Höller ◽  
H. Weber ◽  
H. Breuer

Abstract. The uptake of [4-14C]oestriol by the isolated perfused rat liver is 3.8 times faster as compared to that of simultaneously perfused [6,9-3H2]oestriol 16α-monoglucuronide. During perfusion the concentration of both radioactive oestrogens decreased exponentially in perfusion medium (apparent kel: 0.061 min−1 and 0.016 min−1, respectively). [6,9−3H2]Oestriol 16α-monoglucuronide was metabolized only to a small extent; more than 92% was secreted unchanged into the bile where it was highly concentrated (1800 nmol/g). In contrast [4-14C]oestriol was extensively metabolized; it was mainly hydroxylated at C-atom 2, leading to a rapid increase in the concentration of 2-hydroxyoestriol in the perfused medium. This metabolite was quickly taken up by the liver during recirculation and subsequently either methylated or sulphated. 2-Hydroxyoestriol monosulphate was glucuronated to 2-hydroxyoestriol 16α-monoglucuronide 3-sulphate, which was rapidly excreted into the bile. No double conjugate was formed when [6,9-3H2]oestriol 16α-monoglucuronide was perfused; this is additional evidence for the correctness of the assumption that monoglucuronides cannot serve as precursors of sulphoglucuronides.


1976 ◽  
Vol 230 (3) ◽  
pp. 736-742 ◽  
Author(s):  
Bloomer ◽  
J Zaccaria

Features of hepatic bilirubin transport were studied with the isolated perfused rat liver. Male Wistar rats weighing 350-400 g were used as liver donors. When bilirubin was constantly infused into the perfusion medium, which contained sheep erythrocytes and 3.0 g/100 ml bovine serum albumin, the maximal excretion rate for bilirubin was 14.4 +/- 1.2 mug/min per g liver. Over a wide range of constant bilirubin infusion rates which went as high as 25.9 mug/min per g liver, there was no effect on bile flow, bile acid excretion, or the pattern of bilirubin conjugates in bile. The hepatic extraction efficiency for unconjugated bilirubin from the perfusate also remained constant averaging 26%. However, when bolus injections of bilirubin were used to produce higher levels of unconjugated bilirubin in the perfusate than could be attained during constant infusion, the disappearance rate of [14C]bilirubin from the perfusate decreased with increasing bilirubin concentrations. This was consistent with saturation of the hepatic removal of unconjugated bilirubin.


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