Rate‐Limiting Factors in Ethanol Oxidation by Isolated Rat‐Liver Parenchymal Cells

Grunnet, Niels; Quistorff, Bjørn; Thieden, H. I. D.

doi:10.1111/j.1432-1033.1973.tb03195.x

Cited by 126 publications

(14 citation statements)

References 31 publications

(15 reference statements)

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“…Therefore, there is no evidence that the sudden increase in ethanol metabolism reported in isolated liver cells between concentrations of 40 mM and 65 mM ethanol (19) Liver samples were. taken at 120 min after i.p.…”

Section: Discussionmentioning

confidence: 99%

“…These in vitro data suggest that the rate of ethanol metabolism through the alcohol dehydrogenase pathway and, therefore, the rate of cytoplasmic NADH production would decrease with increasing concentrations of ethanol above 8 mM and that, therefore, the effects of high doses of ethanol on intermediary metabolism in liver might actually be less than those of lower doses. The predictions of the effect of dose are further complicated by in vitro evidence for alternate pathways of ethanol metabolism operative at high ethanol concentrations (17,18) and by nonlinear ethanol metabolism curves also at high levels (19).…”

Section: Ch3ch20h + Nad+ = Ch3cho + Nadh+h+ (1)mentioning

confidence: 99%

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Dependence on dose of the acute effects of ethanol on liver metabolism in vivo.

Guynn¹,

Pieklik²

1975

J. Clin. Invest.

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A B S T Rratio were paradoxically most reduced with the lowest dose of ethanol and became progressively more oxidized with increasing dose. Once established, the differences in these ratios between the groups tended to persist with time, relatively independent of the concentration of ethanol. In a somewhat different pattern, the phosphory-]) remained at the control level in the low-dose group but was significantly elevated in the two higher-dose groups.The results, therefore, show distinct and complicated dose-dependent patterns of intermediary metabolism that cannot be explained completely by any one hypothesis but that imply significant dose-dependent effects of ethanol upon intermediary metabolism not directly related to NADH production.

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Section: Discussionmentioning

confidence: 99%

Section: Ch3ch20h + Nad+ = Ch3cho + Nadh+h+ (1)mentioning

confidence: 99%

Dependence on dose of the acute effects of ethanol on liver metabolism in vivo.

Guynn¹,

Pieklik²

1975

J. Clin. Invest.

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“…This rate was about equal to the capacity of alcohol dehydrogenase, which was 474 +_ 32 pmol ethanol oxidized x (g dry weight)-' x h-' at 37 C ( Table 2). Limitation of ethanol oxidation by alcohol dehydrogenase activity was also reported previously for ethanol oxidation in the presence of pyruvate or fructose [4,28,32].…”

Section: Discussionmentioning

confidence: 95%

“…With dihydroxyacetone present, production of glucose (see below) utilizes ATP and makes ADP available for oxidation of mitochondrial reducing equivalents by oxygen. With glycerol present the total flux of reducing equivalents from cytosol to mitochondria can be calculated as the sum of ethanol uptake, lactate production and twice the amount of glucose produced [30], assuming that oxidation of acetaldehyde occurs in the mitochondria [31] and that the contribution of total ethanol consumption of ethanol oxidation not mediated by alcohol dehydrogenase is relatively small, as appears to be the case [l, 2,6,32]. Under these conditions total hydrogen flux to the mitochondria amounted to 492 pmol x (g dry weight of cells)-' x h-', which includes 28 f 3 pmol lactate formed (not shown in Table 1).…”

Section: Glycerolmentioning

confidence: 99%

The Role of Hydrogen Translocating Shuttles during Ethanol Oxidation in Hepatocytes from Euthyroid and Hyperthyroid Rats

Hensgens

Nieuwenhuis

Meer

et al. 1980

European Journal of Biochemistry

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A quantitative study of the contribution of the malate-aspartate and glycerol-3-phosphate cycles to the translocation of reducing equivalents from cytosol to mitochondria during ethanol oxidation has been made in hepatocytes from euthyroid and hyperthyroid rats.1. In hepatocytes from euthyroid rats both cycles have an almost equal capacity and their relative contribution to total hydrogen transport to the mitochondria depends on the conditions chosen.2. In hepatocytes from hyperthyroid rats maximal rates of ethanol oxidation were significantly lower than in hepatocytes from euthyroid rats, even though the capacity of the glycerol-3-phosphate cycle was increased. This was due to a decreased activity of alcohol dehydrogenase.Three factors can control the rate of hepatic ethanol oxidation : firstly, the activity of alcohol dehydrogenase; secondly, the translocation of reducing equivalents from cytosol to mitochondria; and thirdly, the oxidation of mitochondrial reducing equivalents by oxygen. Depending on the experimental conditions each of these factors can be rate-limiting for ethanol oxidation [l -61. Of the various possible shuttle systems involved in the transport of reducing equivalents from cytosol to mitochondria the malate-aspartate and the glycerol-3-phosphate cycles are presumably quantitatively the most important ones (see [7,8] for reviews). There is, however, no general agreement about the relative importance of these two shuttles during ethanol oxidation. According to Berry and coworkers [5,9] the malate-aspartate cycle plays only a minor role in ethanol oxidation. However, in other reports the contrary is stated [1-3,lO-131. In this paper we describe a quantitative study of the contribution of the malate-aspartate and glycerol-3-phosphate cycles to the translocation of reducing

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“…Ethanol metabolism was assayed by the method of Grunnet et al ( 16). Culture plates were incubated for 6 h with 2 x I05 dpm ['4C]ethanol (10 mM, final concentration) in sealed beakers.…”

Section: Methodsmentioning

confidence: 99%

Iron mediates production of a neutrophil chemoattractant by rat hepatocytes metabolizing ethanol.

Hultcrantz¹,

Bissell²,

Roll³

1991

J. Clin. Invest.

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Ethanol metabolism in hepatocytes is accompanied by release of a potent lipid chemoattractant for neutrophils. Production of the factor may initiate the inflammation associated with alcoholic hepatitis. In previous studies with a cytosol system from liver, production was blocked by iron chelators as well as by catalase and superoxide dismutase, suggesting the involvement of oxyradicals in formation of the chemoattractant. These studies have examined the role of iron in intact hepatocytes using cells from rats fed an iron-deficient diet, a control diet or a diet containing 3% carbonyl iron. The iron content averaged 1.4 nmol/mg protein in iron-deficient cells, 6.3 in controls and 135.3 in iron-loaded cells. Hepatocytes from all groups were established in primary culture and incubated with ethanol (10 mM); the medium was assayed for chemoattractant activity for human neutrophils. Cultures from chow-fed or iron-loaded animals produced chemoattractant as previously reported. By contrast, chemoattractant production was undetectable in the irondeficient cultures. Addition of ferric citrate (10-M) restored chemoattractant production while increasing cellular iron in the deficient cells less than 50% (to 2.3 nmol/mg protein). Addition of desferrioxamine mesylate to cultures of iron-loaded cells ablated chemoattractant production. The data provide evidence for the importance of hepatocellular iron in production of this alcohol-related lipid chemoattractant and suggest that a small intracellular pool of "free" iron plays a critical role. (J. Clin.

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Rate‐Limiting Factors in Ethanol Oxidation by Isolated Rat‐Liver Parenchymal Cells

Cited by 126 publications

References 31 publications

Dependence on dose of the acute effects of ethanol on liver metabolism in vivo.

Dependence on dose of the acute effects of ethanol on liver metabolism in vivo.

The Role of Hydrogen Translocating Shuttles during Ethanol Oxidation in Hepatocytes from Euthyroid and Hyperthyroid Rats

Iron mediates production of a neutrophil chemoattractant by rat hepatocytes metabolizing ethanol.

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