Ethanol Metabolism and Production of Free Acetate in the Human Liver

Lundquist, Frank; Tygstrup, Niels; Winkler, K.; Mellemgaard, Kresten; Munck-Petersen, Sivert

doi:10.1172/jci104574

Cited by 331 publications

(149 citation statements)

References 25 publications

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“…A decrease in hepatic acyl CoA levels under the influence of ethanol has been also reported by Zakim [46] associated with increased fatty acid synthesis, perhaps by altering the acyl CoA mediated inhibition of acetyl CoA carboxylase. The decrease in acetyl CoA levels observed is compatible with nearly unchanged ketone body formation under the influence of ethanol observed here and elsewhere [2]. However, an increase in the acetyl CoA levels has recently been reported after 60 min [47] of ethanol feeding.…”

Section: Discussionsupporting

confidence: 90%

Effects of Ethanol Infusion on the Redox State and Metabolite Levels in Rat Liver in vivo

Rawat¹

1968

European Journal of Biochemistry

108

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1. Hepatic levels of several metabolites of the Embden-Meyerhof pathway, the citric acid cycle and oxidized and reduced substrate pairs of the lactate, a-glycerophosphate, /?-hydroxybutyrate, malate, and glutamate dehydrogenase systems were measured in freeze clamped livers from fed male rats, before and after ethanol infusion.2 3. The levels of pyruvate, acetyl CoA, citrate, and ATP were decreased during ethanol treatment.4. The hepatic levels of glycogen, oxaloacetate, 2-oxoglutarate, ammonia, aspartate, and acetoacetate remained unchanged, 30 min after ethanol infusion, as compared to values before ethanol infusion.5. Hepatic glucose 6-phosphatase activity was significantly increased after 15 min of ethanol infusion (1.5 g/kg body weight). The glucose 6-phosphatase activity showed a maximum 15 min after ethanol infusion, the fructose 1,6 diphosphatase activity did not change significantly 15 and 30 min after ethanol infusion. Hepatic acid and alkaline phosphatase activities measured with /?-glycerophosphate as substrate showed no significant changes compared to values from normal rat livers.6. The presence of ethanol (8 mM) in the incubation medium showed no significant effect on the [6-14C]glucose incorporation into glycogen by the liver slices.The "redox state" of the liver is shifted towards a more reduced state when ethanol is being oxidized. The oxidation of ethanol in the liver results in an increased NADH/NAD ratio both in man and in perfused rat livers [l-31. Information on the value of this ratio a t the site of oxido-reductions is of importance because it bears on the metabolic behaviour of oxidizable and reducible substrates. It is specially relevant to decide the direction of reversible reactions [4].

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Section: Discussionsupporting

confidence: 90%

Effects of Ethanol Infusion on the Redox State and Metabolite Levels in Rat Liver in vivo

Rawat¹

1968

European Journal of Biochemistry

108

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“…I n spite of major differences in basal oxygen consumption, the rate of ethanol oxidation is not appreciably influenced by treatment with triiodothyronine or with propyl thiouracil [21,29,30]. It has been calculated that in a normal liver about 7501, of the oxygen consumption is due to the oxidation of NADH liberated in the breakdown of ethanol to acetate [31,32]. Consequently, the normal CO, production from the tricarboxylic acid cycle is inhibited and the respiratory quotient falls to very low values [6,12,20].…”

Section: Ethanol-induced Changes In the Redox Xtate Inmentioning

confidence: 99%

Interference of Ethanol and Sorbitol with Hepatic Ketone Body Metabolism in Normal, Hyper‐ and Hypothyroid Rats

Lindros

1970

European Journal of Biochemistry

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I . Rats pretreated with triiodothyronine or propylthiouracil were compared with normal rats with respect to the changes induced by ethanol or sorbitol in the levels of ketone bodies and acetyl coenzyme A and in the mitochondrial redox state of the NAD couple in the intact liver after overnight fasting.2. A single dose of ethanol (2.5 g/kg) increased the ketone body level and the acetyl-CoA content after 75 min in both normal and hyperthyroid rats but not in hypothyroid rats.3. Infusion of sorbitol (0.5 g/kg) resulted in decreases in both ketone formation and levels of acetyl-CoA after 15 min in all types of rats.4. The 8-hydroxybutyratelacetoacetate ratio, which represents the redox state of the NAD couple in the mitochondria, was increased more than three-fold by treatment with ethanol in normal rats, but only by 50 in hyperthyroid rats. A ten-fold increase in the redox state of the mitochondria was caused by ethanol in hypothyroid rats, as the result of a strongly diminished acetoacetate level.5. Sorbitol infusion resulted in slight increase of the p-hydroxybutyratelacetoacetate ratio in normal and hypothyroid rats but decreased the ratio in hyperthyroid rats.6. The different ketone body levels observed in these situations were not found to be related to changes in the mitochondrial redox state, but a highly significant correlation ( P < 0.001)was observed between the changes in the content of acetyl-CoA and the ketone bodies.Among the factors suggested to control the rate of ketone body formation in the liver, the intramitochondrial redox state of the NAD couple is currently believed to be one of central importance [I-41. This topic has recently been reviewed by Wieland [5]. The rapid oxidation of fatty acids in different situations of ketonaemia apparently accelerates the intramitochondrial production of NADH. The metabolism of both ethanol and sorbitol is initiated by NADcoupled dehydrogenases located mainly in the cytoplasm, and consequently the oxidation of both of these substrates increases the NADH/NAD+ ratio in the cytoplasm [6--111.

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“…Les mécanismes du catabolisme ont été clairement établis [13,16,34]. Principalement réalisés dans le foie, ils mettent en jeu différents systèmes enzymatiques : alcool-déshydrogénase (EC1.1.1.1 ou alcohol: NAD + oxidoreductase) ; MEOS (microsomal ethanol-oxidizing system : système microsomal [35,36].…”

Section: Discussionunclassified

“…L'acétaldéhyde, produit lors de la première étape, reste pratiquement indécelable dans les prélèvements sanguins, puisqu'il est très rapidement oxydé en acétate libre [15]. Ces acétates sont éliminés du foie par la veine sus-hépatique puis distribués via la circulation artérielle vers les organes extrahépatiques capables de les assimiler, en particulier les muscles squelettiques [16]. Ceci corrobore la différence artérioveineuse de concentration en acétates observée : le sang artériel plus concentré distribue les acétates aux différents tissus qui les utilisent, le sang veineux est donc moins concentré.…”

Section: Discussionunclassified

“…Or, parmi ces mé-tabolites : l'acétate [12] et l'acéto-acétate [13] participeraient aux acidémies ou acidoses observées après alcoolisation. Et, selon certains auteurs, le métabolisme hépatique de l'éthanol déplaçant l'équilibre du cofacteur NAD + /NADH,H + , les lactates hépatiques et sanguins seraient augmentés et participeraient aussi à cette acidose [10,11,[14][15][16][17].…”

Section: Introductionunclassified

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Influence du site de prélèvement sur l’étude cinétique et métabolique de l’éthanol

et al. 2012

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Résumé -Objectif : L'analyste n'obtenant pas toujours les mêmes prélèvements sanguins, nous proposons d'étudier l'influence du site de prélèvement sanguin sur l'étude cinétique et métabolique de l'éthanol. Méthode : Sur un modèle animal, le rat mâle Sprague-Dawley âgé de 7 à 9 semaines, les cinétiques sanguines de l'éthanol, sériques de l'acétate et du lactate, artérielles et veineuses, sont déterminées respectivement par analyse de l'espace de tête en chromatographie en phase gazeuse et électrophorèse capillaire de zone. L'animal est cathétérisé soit au niveau d'une artère fémorale, soit au niveau d'une veine caudale. Résultats : Lors de la phase d'absorption, l'éthanolémie artérielle croît plus rapidement et plus intensément que l'éthanolémie veineuse ; après la phase de distribution, elles tendent à se confondre. Contemporainement, les acétates, métabolites de l'éthanol, apparaissent plus concentrés dans le compartiment artériel que veineux périphérique ; les lactates, produits indirects du métabolisme de l'éthanol, présentent une cinétique artérielle similaire à celle de l'acétate, les concentrations veineuses restant anormalement élevées pendant l'étude. Conclusion : Le sang veineux prélevé lors de cette étude n'a pas donné accès à la réalité cinétique et métabolique de l'éthanol. Ainsi, en comparaison avec le compartiment artériel, l'éthanol et l'acétate sont présents en quantité moindre dans le sang veineux, l'éthanol y apparaissant plus lentement. Le sang veineux prélevé s'est même avéré inadapté à l'étude cinétique des lactates. Cette étude confirme, si nécessaire, que les résultats et l'interprétation d'une analyse sont préconditionnés par le prélèvement lui-même, ce dernier n'étant pas toujours réalisé sous les indications d'un analyste. Mots clés :Recueil de prélèvements sanguins/méthode, éthanol/sang, éthanol/métabolisme, acétates/sang, lactates/sang Abstract -Objective: Because the analyst does not always obtain the same sampling of blood, we suggest studying the influence of the site of blood sampling on kinetic and metabolic studies of ethanol. Method: On an animal model, 7-to-9-week-old Sprague-Dawley male rats, arterial and venous blood kinetics of ethanol and serum kinetics of acetate and lactate were, respectively, determined by head-space chromatography analysis and capillary zone electrophoresis. The animal is catheterized either at the femoral artery, or at the caudal vein. Results: During the absorption phase, the arterial blood ethanol grew more quickly and more intensely than the venous; after the distribution phase, they tended to merge. At the same time, acetates, produced during ethanol metabolism, were more concentrated in the arterial compartment than the venous; lactates, indirect products of ethanol metabolism, presented an arterial kinetics similar to acetate, and venous concentrations remained abnormally high throughout the study. Conclusion: The venous blood samples taken during this study did not give access to the kinetic and metabolic reality of ethanol. So, compared with t...

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Ethanol Metabolism and Production of Free Acetate in the Human Liver

Cited by 331 publications

References 25 publications

Effects of Ethanol Infusion on the Redox State and Metabolite Levels in Rat Liver in vivo

Effects of Ethanol Infusion on the Redox State and Metabolite Levels in Rat Liver in vivo

Interference of Ethanol and Sorbitol with Hepatic Ketone Body Metabolism in Normal, Hyper‐ and Hypothyroid Rats

Influence du site de prélèvement sur l’étude cinétique et métabolique de l’éthanol

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