scholarly journals Rates of ketone-body formation in the perfused rat liver

1969 ◽  
Vol 112 (5) ◽  
pp. 595-600 ◽  
Author(s):  
H. A. Krebs ◽  
Patricia G. Wallace ◽  
R. Hems ◽  
R. A. Freedland
Keyword(s):  
Fatty Acids ◽  
Rat Liver ◽  
Ketone Bodies ◽  
Short Chain Fatty Acids ◽  
Diabetic Rats ◽  
Isolated Perfused Rat Liver ◽  
Perfused Liver ◽  
Perfused Rat Liver ◽  
Normal Range ◽  
Physiological Value

1. The rates of formation of acetoacetate and β-hydroxybutyrate by the isolated perfused rat liver were measured under various conditions. 2. The rates found after addition of butyrate, octanoate, oleate and linoleate were about 100μmoles/hr./g. wet wt. in the liver of starved rats. These rates are much higher than those found with rat liver slices. 3. The differences between the rates given by slices and by the perfused organ were much higher with the long-chain than with short-chain fatty acids. The increments caused by oleate and linoleate were 12 and 16 times as large in the perfused organ as in the slices, whereas the increments caused by butyrate and octanoate were about four times as large. 4. The rates of ketogenesis in the unsupplemented perfused liver of well-fed rats, and the increments caused by the addition of fatty acids, were about half of those in the liver from starved rats. 5. The value of the [β-hydroxybutyrate]/[acetoacetate] ratio of the medium was raised by octanoate, oleate and linoleate. 6. Carnitine did not significantly accelerate ketogenesis from fatty acids. 7. Oleate formed up to 82% of the expected yield of ketone bodies. 8. In the liver of alloxan-diabetic rats the endogenous rates of ketogenesis were raised, in some cases as high as in the liver from starved rats, after addition of oleate. 9. On addition of either β-hydroxybutyrate or acetoacetate to the perfusion medium the liver gradually adjusted the [β-hydroxybutyrate]/[acetoacetate] ratio towards the normal range. 10. The [β-hydroxybutyrate]/[acetoacetate] ratio of the medium was about 0·4 when slices were incubated, but near the physiological value of 2 when the liver was perfused. 11. The experiments demonstrate that for the study of ketogenesis slices are in many ways grossly inferior to the perfused liver.

Biliary excretion of dihydro-11-keto-progesterone-4-C14 by isolated perfused liver

1964 ◽  
Vol 207 (5) ◽  
pp. 1030-1034 ◽  
Author(s):  
G. F. Leong ◽  
D. M. Cazes ◽  
M. L. Berliner ◽  
D. L. Berliner
Keyword(s):  
Rat Liver ◽  
Biliary Excretion ◽  
Half Life ◽  
Water Soluble ◽  
Isolated Perfused Rat Liver ◽  
Perfused Liver ◽  
Rapid Rate ◽  
Perfused Rat Liver ◽  
Bile Formation ◽  
Entire Study

The rates of biliary excretion of dihydro-11-keto-progesterone-4-C14 and of its metabolites were studied in the isolated perfused rat liver. The half-life of this steroid in the perfusing blood was 2.5 min, and at 40 min about 75% of the injected steroid had been excreted in bile. Formation of water-soluble steroids (WS St) took place at a rapid rate and by 60 min 100% of the steroids in blood were found to be water soluble. During the entire study the steroids excreted in bile were water soluble and accounted for 97.2–100% (avg. 98.2%). No dihydro-11-keto-progesterone was found to be excreted in the bile. The rate of disappearance from the blood, excretion in the bile, and degree of formation of WS St of this compound when compared with corticosterone and cortisol shows the following pattern: dihydro-11-keto-progesterone > corticosterone > cortisol.

scholarly journals Fatty acid metabolism in the perfused rat liver

1970 ◽  
Vol 119 (3) ◽  
pp. 525-533 ◽  
Author(s):  
H. A. Krebs ◽  
R. Hems
Keyword(s):  
Fatty Acids ◽  
Rat Liver ◽  
Ketone Body ◽  
Unsaturated Fatty Acids ◽  
Ketone Bodies ◽  
Saturated Fatty Acids ◽  
Perfused Rat Liver ◽  
Body Formation ◽  
Body Production ◽  
Chain Fatty Acids

1. The formation of acetoacetate, β-hydroxybutyrate and glucose was measured in the isolated perfused rat liver after addition of fatty acids. 2. The rates of ketone-body formation from ten fatty acids were approximately equal and independent of chain length (90–132μmol/h per g), with the exception of pentanoate, which reacted at one-third of this rate. The [β-hydroxybutyrate]/[acetoacetate] ratio in the perfusion medium was increased by long-chain fatty acids. 3. Glucose was formed from all odd-numbered fatty acids tested. 4. The rate of ketone-body formation in the livers of rats kept on a high-fat diet was up to 50% higher than in the livers of rats starved for 48h. In the livers of fat-fed rats almost all the O2 consumed was accounted for by the formation of ketone bodies. 5. The ketone-body concentration in the blood of fat-fed rats rose to 4–5mm and the [β-hydroxybutyrate]/[acetoacetate] ratio rose to 11.5. 6. When the activity of the microsomal mixed-function oxidase system, which can bring about ω-oxidation of fatty acids, was induced by treatment of the rat with phenobarbitone, there was no change in the ketone-body production from fatty acids, nor was there a production of glucose from even-numbered fatty acids. The latter would be expected if ω-oxidation occurred. Thus ω-oxidation did not play a significant role in the metabolism of fatty acids. 7. Arachidonate was almost quantitatively converted into ketone bodies and yielded no glucose, demonstrating that gluconeogenesis from poly-unsaturated fatty acids with an even number of carbon atoms does not occur. 8. The rates of ketogenesis from unsaturated fatty acids (sorbate, undecylenate, crotonate, vinylacetate) were similar to those from the corresponding saturated fatty acids. 9. Addition of oleate together with shorter-chain fatty acids gave only a slightly higher rate of ketone-body formation than oleate alone. 10. Glucose, lactate, fructose, glycerol and other known antiketogenic substances strongly inhibited endogenous ketogenesis but had no effects on the rate of ketone-body formation in the presence of 2mm-oleate. Thus the concentrations of free fatty acids and of other oxidizable substances in the liver are key factors determining the rate of ketogenesis.

scholarly journals Peroxisomal fatty acid oxidation as detected by H2O2 production in intact perfused rat liver

1981 ◽  
Vol 196 (3) ◽  
pp. 705-712 ◽  
Author(s):  
E C Foerster ◽  
T Fährenkemper ◽  
U Rabe ◽  
P Graf ◽  
H Sies
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Rat Liver ◽  
Hydrogen Donor ◽  
High Yield ◽  
Acid Oxidation ◽  
Isolated Perfused Rat Liver ◽  
H2o2 Production ◽  
Perfused Rat Liver ◽  
H2o2 Formation

1. H2O2 formation associated with the metabolism of added fatty acids was quantitatively determined in isolated haemoglobin-free perfused rat liver (non-recirculating system) by two different methods. 2. Organ spectrophotometry of catalase Compound I [Sies & Chance (1970) FEBS Lett. 11, 172-176] was used to detect H2O2 formation (a) by steady-state titration with added hydrogen donor, methanol or (b) by comparison of fatty-acid responses with those of the calibration compound, urate. 3. In the use of the peroxidatic reaction of catalase, [14C]methanol was added as hydrogen donor at an optimal concentration of 1 mM in the presence of 0.2 mM-L-methionine, and 14CO2 production rates were determined. 4. Results obtained by the different methods were similar. 5. The yield of H2O2 formation, expressed as the rate of H2O2 formation in relation to the rate of fatty-acid supply, was less than 1.0 in all cases, indicating that, regardless of chain length, less than one acetyl unit was formed per mol of added fatty acid by the peroxisomal system. In particular, the standard substrate used with isolated peroxisomal preparations (C16:0 fatty acid) gave low yield (close to zero). Long-chain monounsaturated fatty acids exhibit a relatively high yield of H2O2 formation. 6. The hypolipidaemic agent bezafibrate led to slightly increased yields for most of the acids tested, but the yield with oleate was decreased to one-half the original yield. 7. It is concluded that in the intact isolated perfused rat liver the assayable capacity for peroxisomal beta-oxidation is used to only a minor degree. However, the observed rates of H2O2 production with fatty acids can account for a considerable share of the endogenous H2O2 production found in the intact animal.

Lipogenesis from ketone bodies in the perfused rat liver: effects of acetate and ethanol

1987 ◽  
Vol 65 (11) ◽  
pp. 989-996 ◽  
Author(s):  
Gerda Endemann ◽  
Patrick G. Goetz ◽  
John F. Tomera ◽  
William M. Rand ◽  
Sylvain Desrochers ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Rat Liver ◽  
Ketone Body ◽  
Ketone Bodies ◽  
The Other ◽  
Ethanol Metabolism ◽  
Perfused Rat Liver ◽  
Other Hand

The interactions between acetate or ethanol metabolism, lipogenesis, and ketone body utilization have been studied in isolated livers from fed rats perfused with 15 mM glucose and 10 mM acetate or ethanol. The contribution of acetate to ketogenesis is constant; on the other hand, the contribution of ethanol to ketogenesis increases with time, presumably because of the accumulation of acetate in the perfusate. Ketogenesis is decreased in the presence of ethanol (but not acetate), while ketone body utilization is not affected by ethanol or acetate. Acetate contributes one third and ethanol contributes one half of the carbon incorporated into fatty acids and 3-β-hydroxysterols. Only a small fraction (less than 5%) of the incorporation of acetate or ethanol into fatty acids and sterols occurs via transient incorporation into ketone bodies.

The utilization of ethanol by the isolated perfused rat liver

1968 ◽  
Vol 46 (4) ◽  
pp. 609-616 ◽  
Author(s):  
Ellen R. Gordon
Keyword(s):  
Rat Liver ◽  
Ethanol Consumption ◽  
Isolated Perfused Rat Liver ◽  
Gas Mixture ◽  
Perfused Liver ◽  
Perfused Rat Liver ◽  
Isolated Perfused Liver ◽  
Partial Pressures ◽  
Series Of Experiments ◽  
Lactic Acids

A series of experiments has shown that the mechanisms by which the metabolism of ethanol occurs are strongly influenced by the partial pressures of the oxygen present in the aerating medium. For the most frequently used gas mixture, 95% O2 + 5% CO2, the ethanol consumption was abnormally large, and proportional to the concentration of ethanol in the perfusate. However, when the system was aerated with 18% O2 + 5% CO2 + 77% N2 the consumption of ethanol was similar to that found in the intact rat. The perfusate concentration of glucose, acetone, and acetic, pyruvic, and lactic acids was measured in all experiments. When ethanol was consumed at these two different rates, increases in the lactic: pyruvic ratio and acetate levels of the perfusate were noted in both types of experiments. However, the utilization of glucose by isolated perfused liver was inhibited, and acetone levels increased markedly, when ethanol was consumed at abnormally rapid rates, although no effect was noted in the perfusate levels of these metabolites when ethanol was consumed at normal rates.

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