scholarly journals Utilization and metabolic effects of acetaldehyde and ethanol in the perfused rat liver

1972 ◽  
Vol 126 (4) ◽  
pp. 945-952 ◽  
Author(s):  
K. O. Lindros ◽  
R. Vihma ◽  
O. A. Forsander
Keyword(s):  
Maximum Rate ◽  
Ethanol Oxidation ◽  
Gradual Increase ◽  
Metabolic Effects ◽  
Redox Equilibrium ◽  
Low Concentrations ◽  
Mitochondrial Oxidation ◽  
Ethanol Removal ◽  
Rat Livers ◽  
Pyruvate Ratio

1. Removal of acetaldehyde and ethanol has been studied in perfused rat livers. 2. The maximum rate of ethanol oxidation was 2μmol/min per g of liver, which was less than the calculated capacity of the ethanol-oxidizing system. The lactate/pyruvate ratio of the medium increased with the rate of ethanol removal. At low ethanol concentrations most of the acetaldehyde formed was oxidized further, but at ethanol concentrations above 16mm about 60% of the acetaldehyde left the liver unmetabolized. 3. At lower concentrations the greater part of added acetaldehyde was oxidized, but above 5mm, 50–60% of that removed was recovered as ethanol. 4. When the reduction of acetaldehyde was blocked by pyrazole, removal was strongly diminished. There was no effect on the lactate/pyruvate ratio during oxidation of low concentrations of acetaldehyde, even in the presence of pyrazole, but at higher concentrations a gradual increase occurred. 5. The results indicate that during ethanol oxidation the ethanol/acetaldehyde pair is not in redox equilibrium with the lactate/pyruvate pair. Ethanol oxidation was abolished by addition of acetaldehyde. Under these conditions the lactate/pyruvate ratio was 1.5–1.8 times the ethanol/acetaldehyde ratio, indicating equilibration of the alcohol dehydrogenase and lactate dehydrogenase systems. 6. The results support the view that ultimately the rate of mitochondrial oxidation of NADH limits the removal of ethanol in the liver.

Mechanisms of vanadium action: insulin-mimetic or insulin-enhancing agent?

2000 ◽  
Vol 78 (10) ◽  
pp. 829-847 ◽  
Author(s):  
Margaret C Cam ◽  
Roger W Brownsey ◽  
John H McNeill
Keyword(s):  
Lipid Metabolism ◽  
Metabolic Effects ◽  
Isolated Cells ◽  
Insulin Mimetic ◽  
Endogenous Insulin ◽  
Carbohydrate And Lipid Metabolism ◽  
Low Concentrations ◽  
Tissue Sensitivity ◽  
High Concentrations

The demonstration that the trace element vanadium has insulin-like properties in isolated cells and tissues and in vivo has generated considerable enthusiasm for its potential therapeutic value in human diabetes. However, the mechanisms by which vanadium induces its metabolic effects in vivo remain poorly understood, and whether vanadium directly mimics or rather enhances insulin effects is considered in this review. It is clear that vanadium treatment results in the correction of several diabetes-related abnormalities in carbohydrate and lipid metabolism, and in gene expression. However, many of these in vivo insulin-like effects can be ascribed to the reversal of defects that are secondary to hyperglycemia. The observations that the glucose-lowering effect of vanadium depends on the presence of endogenous insulin whereas metabolic homeostasis in control animals appears not to be affected, suggest that vanadium does not act completely independently in vivo, but augments tissue sensitivity to low levels of plasma insulin. Another crucial consideration is one of dose-dependency in that insulin-like effects of vanadium in isolated cells are often demonstrated at high concentrations that are not normally achieved by chronic treatment in vivo and may induce toxic side effects. In addition, vanadium appears to be selective for specific actions of insulin in some tissues while failing to influence others. As the intracellular active forms of vanadium are not precisely defined, the site(s) of action of vanadium in metabolic and signal transduction pathways is still unknown. In this review, we therefore examine the evidence for and against the concept that vanadium is truly an insulin-mimetic agent at low concentrations in vivo. In considering the effects of vanadium on carbohydrate and lipid metabolism, we conclude that vanadium acts not globally, but selectively and by enhancing, rather than by mimicking the effects of insulin in vivo.Key words: vanadium, insulin-mimetic, insulin-like, insulin-enhancing.

H+ current response to CO2 and carbonic anhydrase inhibition in turtle bladder

1976 ◽  
Vol 231 (2) ◽  
pp. 565-572 ◽  
Author(s):  
JH Schwartz
Keyword(s):  
Carbonic Anhydrase ◽  
Maximum Rate ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Current Response ◽  
Low Concentrations ◽  
Ph Stat ◽  
High Concentrations ◽  
Co2 Addition

To evaluate the role of CO2 and carbonic anhydrase (CA) in H+ transport (JH) by turtle urinary bladder the effect of CO2 addition, with and without addition of CA inhibitiors, was examined on JH. Since in the presence of exogenous CO2 and HCO3- the pH stat-measured rate of mucosal (M) acidification underestimates JH by the rate of electroneutral HCO3- secretion, the reverse short-circuit current (RSCC) applied across ouabain-treated bladders was used to estimate JH. That the RSCC is a measure of JH was demonstrated by: 1) in the absence of added CO2 and HCO3- the rate of M acidification totally accounted for the RSCC, and 2) increases in RSCC with CO2 addition occurred without changes in Na+ and K+ fluxes or the coupled ration of HCO3- secretion for Cl-absorption. When serosal (S) percent CO2 was progressively progressively increased JH achieved a maximum rate of 64 +/- 3 muA (SE) with 4.5% CO2. At higher S percent CO2 JH did not change, suggesting that factors other than the rate of CO2 hydration were rate limiting. The maximum rate of JH was not decreased by low concentrations of CA inhibitors (acetazolamide, 5 X 10(-5) M), although the percent CO2 at which this maximum rate occurred increased to 8.5%. The increased percent CO2 requirement for the maximum rate of JH with low concentrations of CA inhibitors suggests that these agents alter JH by decreasing the rate of enzymatic CO2 hydration. At high concentrations (acetazolamide, 5 X 10(-4) M) these inhibitors decrease the maximum rate of JH in the presence of CO2, implying that these inhibitors at higher concentrations directly interfere with the H+ transport system.

scholarly journals The metabolic effects of sodium dichloroacetate in the starved rat

1974 ◽  
Vol 142 (2) ◽  
pp. 279-286 ◽  
Author(s):  
Perry J. Blackshear ◽  
Paul A. H. Holloway ◽  
K. George M. M. Albert
Keyword(s):  
Blood Glucose ◽  
Ketone Body ◽  
Metabolic Effects ◽  
Plasma Insulin Concentration ◽  
Hepatic Glucose ◽  
Extrahepatic Tissues ◽  
Lactate And Pyruvate ◽  
Gluconeogenic Substrates ◽  
Net Release ◽  
Pyruvate Ratio

1. Sodium dichloroacetate (300mg/kg body wt. per h) was infused in 24h-starved rats for 4h. 2. Blood glucose decreased significantly, an effect that had previously only been noted in diabetic animals 3. Plasma insulin concentration decreased by 63% blood lactate and pyruvate concentrations decreased by 50 and 33%, whereas concentrations of 3-hydroxybutyrate and acetoacetate increased by 81 and 73% respectively. 4. Livers were freeze-clamped at the end of the 4h infusion. There were significant decreases in hepatic [glucose], [glucose 6-phosphate], [2-phosphoglycerate], the [lactate]/[pyruvate] ratio, [citrate] and [malate], and also [alanine], [glutamate] and [glutamine], suggesting a diminished supply of gluconeogenic substrates. 5. Animals subjected to a functional hepatectomy at the end of 2h infusions showed no difference in blood-glucose disappearance but a highly significant decrease in the rate of accumulation of lactate, pyruvate, glycerol and alanine, compared with control animals. Dichloroacetate decreased ketone-body clearance. 6. After functional hepatectomy an increase in glutamine accumulation appeared to compensate for the decrease in alanine accumulation. 7. It is concluded that dichloroacetate causes hypoglycaemia by decreasing the net release of gluconeogenic precursors from extrahepatic tissues while inhibiting peripheral ketone-body uptake. 8. These findings are consistent with the activation of pyruvate dehydrogenase (EC 1.2.4.1) in rat muscle by dichloroacetate previously described by Whitehouse & Randle (1973).

scholarly journals Cholesterol 7α-hydroxylase in rat liver microsomal preparations

1972 ◽  
Vol 128 (1) ◽  
pp. 1-9 ◽  
Author(s):  
K. A. Mitropoulos ◽  
S. Balasubramaniam
Keyword(s):  
Fatty Acids ◽  
Molecular Oxygen ◽  
Rat Liver ◽  
Main Product ◽  
Subcellular Fractions ◽  
Native Protein ◽  
Low Concentrations ◽  
Rat Livers ◽  
Double Isotope

Subcellular fractions containing microsomes prepared from rat livers homogenized in the absence of EDTA catalysed the oxidation of cholesterol to 7α-hydroxycholesterol, 7-oxocholesterol, 7β-hydroxycholesterol and 5α-cholestane-3β,5,6β-triol. These reactions required native protein, molecular oxygen and NADPH. It is suggested that these compounds are formed by a peroxidation analogous to the peroxidation of fatty acids catalysed by liver microsomal preparations. Incubations of [4-14C]cholesterol with microsomal preparations from rat liver homogenized in the presence of EDTA gave 7α-hydroxy[14C]cholesterol as the main product. This reaction required molecular oxygen and NADPH, and was inhibited by CO. The mass of 7α-hydroxycholesterol formed during the incubation was measured by a double-isotope-derivative dilution procedure. This procedure was used to assay the activity of cholesterol 7α-hydroxylase and to measure low concentrations of endogenous 7α-hydroxycholesterol in liver.

scholarly journals Some properties of an alcohol dehydrogenase partially purified from baker's yeast grown without added zinc

1976 ◽  
Vol 153 (2) ◽  
pp. 309-319 ◽  
Author(s):  
C J Dickenson ◽  
F M Dickinson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Alcohol Dehydrogenase ◽  
Maximum Rate ◽  
Ethanol Oxidation ◽  
Competitive Inhibitor ◽  
Baker’S Yeast ◽  
Baker's Yeast ◽  
Kinetic Characteristics ◽  
Yeast Saccharomyces Cerevisiae ◽  
Mechanism Of Catalysis

Alcohol dehydrogenase was partially purified from yeast (Saccharomyces cerevisiae) grown in the presence of 20 μM-MnSO4 without added Zn2+ and from yeast grown in the presence of 1.8 μM-MnSO4. The enzyme from yeast grown with added Zn2+ has the same properties as the crystalline enzyme from commercial supplies of baker's yeast. The enzyme from yeast grown without added An2+ has quite different properties. It has a mol.wt. in the region of 72000 and an S 20 w of 5.8S. The values can be compared with a mol.wt. of 141000 and an S 20 w of 7.6S for the crystalline enzyme. ADP-ribose, a common impurity in commercial samples of NAD+, is a potent competitive inhibitor of the new enzyme (K1 = 0.5 μM), but is not so for the crystalline enzyme. The observed maximum rate of ethanol oxidation at pH 7.05 and 25 degrees C was decreased 12-fold by the presence of 0.06 mol of inhibitor/mol of NAD+ when using the enzyme from Zn2+-deficient yeast, but with crystalline enzyme the maximum rate was essentially unchanged by this concentration of inhibitor. The kinetic characteristics for the two enzymes with ethanol, butan-1-ol, acetaldehyde and butyraldehyde as substrates are markedly different. These kinetic differences are discussed in relation to the mechanism of catalysis for the enzyme from Zn2+-deficient yeast.

scholarly journals Metabolic effects of d-glyceraldehyde in isolated hepatocytes

1986 ◽  
Vol 240 (3) ◽  
pp. 771-776 ◽  
Author(s):  
S M Maswoswe ◽  
F Daneshmand ◽  
D R Davies
Keyword(s):  
Fold Increase ◽  
Isolated Hepatocytes ◽  
High Rate ◽  
Metabolic Effects ◽  
Temporary Increase ◽  
Dihydroxyacetone Phosphate ◽  
Phosphate Content ◽  
Intracellular Content ◽  
Fructose 1,6 Bisphosphate ◽  
Pyruvate Ratio

The effects of D-glyceraldehyde on the hepatocyte contents of various metabolites were examined and compared with the effects of fructose, glycerol and dihydroxyacetone, which all enter the glycolytic/gluconeogenic pathways at the triose phosphate level. D-Glyceraldehyde (10 MM) caused a substantial depletion of hepatocyte ATP, as did equimolar concentrations of fructose and glycerol. D-Glyceraldehyde and fructose each caused a 2-fold increase in fructose 1,6-bisphosphate and the accumulation of millimolar quantities of fructose 1-phosphate in the cells. D-Glyceraldehyde caused an increase in the glycerol 3-phosphate content and a decrease in the dihydroxyacetone phosphate content, whereas dihydroxyacetone increased the content of both metabolites. The increase in the [glycerol 3-phosphate]/[dihydroxyacetone phosphate] ratio caused by D-glyceraldehyde was not accompanied by a change in the cytoplasmic [NAD+]/[NADH] ratio, as indicated by the unchanged [lactate]/[pyruvate] ratio. The accumulation of fructose 1-phosphate from D-glyceraldehyde and dihydroxyacetone phosphate in the hepatocyte can account for the depletion of the intracellular content of the latter. Presumably ATP is depleted as the result of the accumulation of millimolar amounts of a phosphorylated intermediate, as is the case with fructose and glycerol. It is suggested that the accumulation of fructose 1-phosphate during hepatic fructose metabolism is the result of a temporary increase in the D-glyceraldehyde concentration because of the high rate of fructose phosphorylation compared with triokinase activity. The equilibrium constant of aldolase favours the formation and thus the accumulation of fructose 1-phosphate.

scholarly journals Potentiation by ammonia of the metabolic effects of pent-4-enoate in isolated rat hepatocytes

1984 ◽  
Vol 224 (1) ◽  
pp. 263-267 ◽  
Author(s):  
F X Coudé ◽  
G Grimber ◽  
P Parvy ◽  
D Rabier ◽  
J Bardet
Keyword(s):  
Cellular Metabolism ◽  
Rat Hepatocytes ◽  
Metabolic Effects ◽  
Maximum Effect ◽  
Half Maximum ◽  
Isolated Rat Hepatocytes ◽  
Glucose Synthesis ◽  
Beta Hydroxybutyrate ◽  
Isolated Rat ◽  
Pyruvate Ratio

The metabolic effects of pent-4-enoate were studied in isolated rat hepatocytes; 1 mM-pent-4-enoate did not significantly inhibit gluconeogenesis from lactate, alanine and glycerol, but significantly decreased glucose synthesis from pyruvate. The addition of 1 mM-NH4Cl led to a drastic inhibition of glucose synthesis from all these substrates. In hepatocytes incubated with 10 mM-alanine and 1 mM-oleate, pent-4-enoate at 0.05-1 mM slightly inhibited glucose synthesis and ketogenesis. The addition of ammonia resulted in a dramatic potentiation of the metabolic effects of pent-4-enoate. Half-maximum effect of ammonia was observed at 0.2 mM concentration. Concomitant cellular concentrations of ATP and acetyl-CoA were also decreased by the addition of ammonia, as were lactate/pyruvate ratio and beta-hydroxybutyrate/acetoacetate ratio. These data suggest that ammonia seriously interferes with the cellular metabolism of pent-4-enoate and leads to a dramatic potentiation of its effects.

scholarly journals Lactate-stimulated ethanol oxidation in isolated hepatocytes

1978 ◽  
Vol 172 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Kathryn E. Crow ◽  
Neal W. Cornell ◽  
Richard L. Veech
Keyword(s):  
Ethanol Oxidation ◽  
Lactate Concentration ◽  
Isolated Hepatocytes ◽  
Cell Preparation ◽  
O2 Uptake ◽  
Glucose Synthesis ◽  
The Relationship ◽  
Pyruvate Ratio ◽  
Stimulation Of

1. Hepatocytes isolated from starved rats and incubated without other substrates oxidized ethanol at a rate of 0.8–0.9μmol/min per g wet wt. of cells. Addition of 10mm-lactate increased this rate 2-fold. 2. Quinolinate (5mm) or tryptophan (1mm) decreased the rate of gluconeogenesis with 10mm-lactate and 8mm-ethanol from 0.39 to 0.04–0.08μmol/min per g wet wt. of cells, but rates of ethanol oxidation were not decreased. From these results it appears that acceleration of ethanol oxidation by lactate is not dependent upon the stimulation of gluconeogenesis and the consequent increased demand for ATP. 3. As another test of the relationship between ethanol oxidation and gluconeogenesis, the initial lactate concentration was varied from 0.5mm to 10mm and pyruvate was added to give an initial [lactate]/[pyruvate] ratio of 10. This substrate combination gave a large stimulation of ethanol oxidation (from 0.8 to 2.6μmol/min per g wet wt. of cells) at low lactate concentrations (0.5–2.0mm), but rates remained nearly constant (2.6–3.0μmol/min per g wet wt. of cells) at higher lactate concentrations (2.0–10mm). 4. In contrast, owing to the presence of ethanol, the rate of glucose synthesis was only slightly increased (from 0.08 to 0.12μmol/min per g wet wt. of cells) between 0.5mm- and 2.0mm-lactate and continued to increase (from 0.12 to 0.65μmol/min per g wet wt. of cells) with lactate concentrations between 2 and 10mm. 5. In the presence of ethanol, O2 uptake increased with increasing substrate concentration over the entire range. 6. Changes in concentrations of glutamate and 2-oxoglutarate closely paralleled changes in the rate of ethanol oxidation. 7. In isolated hepatocytes, rates of ethanol oxidation are lower than those in vivo apparently because of depletion of malate–aspartate shuttle intermediates during cell preparation. Rates are returned to those observed in vivo by substrates that increase the intracellular concentration of shuttle metabolites.

scholarly journals Evidence that Ca2+ fluxes and respiratory, glycogenolytic and vasoconstrictive effects induced by the action of platelet-activating factor and l-α-lysophosphatidylcholine in the perfused rat liver are mediated by products of the cyclo-oxygenase pathway

1987 ◽  
Vol 245 (1) ◽  
pp. 145-150 ◽  
Author(s):  
J G Altin ◽  
P Dieter ◽  
F L Bygrave
Keyword(s):  
Maximum Rate ◽  
Physiological Responses ◽  
Portal Pressure ◽  
Platelet Activating Factor ◽  
Cell Types ◽  
Maximal Response ◽  
Perfused Rat Liver ◽  
Glucose Output ◽  
Rat Livers ◽  
By Products

The administration of ‘acetylglyceryl ether phosphorylcholine’ (AGEPC, also known as platelet-activating factor) and L-alpha-lysophosphatidylcholine (LPC) to rat livers perfused with media containing 1.3 mM-Ca2+ was followed by a concentration-dependent efflux of Ca2+ from the liver. Near-maximal response was observed at 100 nM-AGEPC and 50 microM-LPC, and resulted in a net efflux of approx. 130 nmol of Ca2+/g of liver. Onset of Ca2+ efflux occurred about 10 s after AGEPC and LPC administration, reached a maximum after about 50 s (the maximum rate of efflux was approx. 180 nmol/min per g) and thereafter decreased rapidly, and was sometimes followed by a much smaller influx of Ca2+. Sequential infusions of AGEPC or LPC, and phenylephrine, indicate that each of these agents mobilizes Ca2+ from the same intracellular source. The efflux of Ca2+ was not observed in the presence of indomethacin or bromophenacyl bromide, or when the liver was perfused with low-Ca2+-containing (25 microM) media. Other physiological responses, such as changes in respiration, glucose output and portal pressure, were also inhibited under these conditions. The results suggest that the Ca2+-flux changes and other responses are mediated by prostaglandins produced and released within the liver, possibly by cell types other than hepatocytes.

scholarly journals INHIBITION OF ESCHERICHIA COLI BY p-AMINOBENZOIC ACID AND ITS REVERSAL BY p-HYDROXYBENZOIC ACID

1951 ◽  
Vol 94 (3) ◽  
pp. 243-254 ◽  
Author(s):  
Bernard D. Davis
Keyword(s):  
Shikimic Acid ◽  
Growth Inhibitor ◽  
Metabolic Effects ◽  
Hydroxybenzoic Acid ◽  
Aminobenzoic Acid ◽  
Chlorobenzoic Acid ◽  
E Coli ◽  
Nitrobenzoic Acid ◽  
Low Concentrations ◽  
High Concentrations

p-Aminobenzoic acid (PABA) exerts three metabolic effects on E. coli: it acts as a normal vitamin at low concentrations, as a source of another vitamin, p-hydroxybenzoic acid (POB), at moderate concentrations, and as a growth inhibitor at high concentrations (150 to 1600 µg./ml.). The inhibition is competitively reversed by POB in 1/100 the concentration of PABA. The inhibition is also reversed to a limited extent by shikimic acid and compound X, precursors of POB. p-Nitrobenzoic acid is an inhibitory competitor of both POB and PABA. The retardation of growth produced by PABA and other competitive analogues of POB (p-nitrobenzoic acid; 4,4'-dihydroxydiphenyl sulfone; phenosulfazole) is converted to complete bacteriostasis by the addition of L-aspartic acid in a remarkably low concentration (1 µg./ml.)) without change in the competitive ratio with POB. The mechanism underlying this synergism is not clear. In contrast to wild type, mutants that require POB not only are inhibited by much lower concentrations of the above analogues, but also show inhibition by weaker competitors of POB such as p-hydroxybenzenesulfonamide, p-chlorobenzoic acid, and p-fluorobenzoic acid.

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