The adaptive increase in ethanol metabolism due to pretreatment with ethanol: A rapid phenomenon

Thurman, Ronald G.; Yuki, Takehiko; Bleyman, Michael; Wendell, Gary D.

doi:10.1016/0376-8716(79)90052-8

Cited by 27 publications

(16 citation statements)

References 9 publications

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“…In some situations, global suppression of mitochondrial metabolism and metabolite exchange occurs, as described for apoptosis, 50,51 ischemia–anoxia, 52–54 cytopathic hypoxia of sepsis and multiple organ failure, 55,56 aerobic glycolysis in cancer cells (Warburg effect) 57,58 and possibly resting pancreatic beta cells 59,60 . After high ethanol ingestion, hepatic mitochondrial respiration increases and ethanol oxidation nearly doubles, which promotes the two‐step metabolism of ethanol first to acetaldehyde by alcohol dehydrogenase (ADH) in the cytosol and then to acetate by acetaldehyde dehydrogenase (ACDH) in the mitochondrial matrix space 61–63 . Increased oxygen consumption should, in theory, lead to increased ATP formation, but to the contrary, ATP declines and glycolysis becomes activated.…”

Section: Vdac: Governator Of Mitochondrial Metabolismmentioning

confidence: 99%

Modulation of mitochondrial membrane permeability in pathogenesis, autophagy and control of metabolism

Lemasters¹

2007

J of Gastro and Hepatol

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The mitochondrial inner and outer membranes have contrasting permeability characteristics. The outer membrane is non-specifically permeable to all low-molecular-weight solutes, whereas the inner membrane is impermeable except through specific transporters. After stresses and sometimes in normal physiology, the permeability of the two membranes can reverse. In the inner membrane, permeability transition pores open to cause the mitochondrial permeability transition (MPT). As the MPT involves more and more mitochondria, autophagy, apoptosis and necrosis progressively develop linked to the proportion of mitochondria injured and the extent of adenosine triphosphate (ATP) depletion, a phenomenon of necrapoptosis. By contrast, the outer membrane may decrease its permeability after certain stresses via closure of voltage-dependent anion channels (VDAC). The VDAC closure globally suppresses mitochondrial function to prevent futile ATP hydrolysis in hypoxia-ischemia and possibly the release of toxic superoxide under conditions of oxidative stress. The VDAC closure may also facilitate selective oxidation of acetaldehyde after ethanol exposure and promote aerobic glycolysis in cancer cells. By contrast, VDAC opening is proposed to stimulate oxidative phosphorylation and promote insulin release by glucose-stimulated pancreatic beta cells. Thus, VDAC serves as a global regulator, or governator, of mitochondrial function. Understanding of how these mitochondrial membrane permeability changes are themselves regulated remains incomplete and requires future study.

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Section: Vdac: Governator Of Mitochondrial Metabolismmentioning

confidence: 99%

Modulation of mitochondrial membrane permeability in pathogenesis, autophagy and control of metabolism

Lemasters¹

2007

J of Gastro and Hepatol

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“…, 5 g/kg i.g. in rats) [79,92]. Since ethanol oxidation is obligatorily linked to NAD + supply, mitochondrial respiration causing NADH oxidation also nearly doubles in SIAM.…”

Section: Vdac and Ethanol Metabolismmentioning

confidence: 99%

Regulation of mitochondrial function by voltage dependent anion channels in ethanol metabolism and the Warburg effect

Lemasters

Holmuhamedov

Czerny

et al. 2012

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Voltage dependent anion channels (VDAC) are highly conserved proteins that are responsible for permeability of the mitochondrial outer membrane to hydrophilic metabolites like ATP, ADP and respiratory substrates. Although previously assumed to remain open, VDAC closure is emerging as an important mechanism for regulation of global mitochondrial metabolism in apoptotic cells and also in cells that are not dying. During hepatic ethanol oxidation to acetaldehyde, VDAC closure suppresses exchange of mitochondrial metabolites, resulting in inhibition of ureagenesis. In vivo, VDAC closure after ethanol occurs coordinately with mitochondrial uncoupling. Since acetaldehyde passes through membranes independently of channels and transporters, VDAC closure and uncoupling together foster selective and more rapid oxidative metabolism of toxic acetaldehyde to nontoxic acetate by mitochondrial aldehyde dehydrogenase. In single reconstituted VDAC, tubulin decreases VDAC conductance, and in HepG2 hepatoma cells, free tubulin negatively modulates mitochondrial membrane potential, an effect enhanced by protein kinase A. Tubulin-dependent closure of VDAC in cancer cells contributes to suppression of mitochondrial metabolism and may underlie the Warburg phenomenon of aerobic glycolysis.

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“…However, from study in the rates of ethanol metabolism in hamsters with high alcohol preference and rats with low alcohol preference, it has been recently indicated that a correlation does exist between alcohol preference and rate of metabolism (47,83). In addition, Thurman et al (76) reported that from non-SIAM (swift increase in ethanol metabolism: SIAM) parents, no Fl progeny exhibited SIAM, whereas all Fl progeny from high SIAM parents exhibited SIAM and established that SIAM is heritable. Endo et al (15) demonstrated that the ethanol elimination rate of C57BL/6J mice with high liver ADH activity is significantly faster than that of NZB mice with low liver ADH activity.…”

Section: Efct Of Long-term Ethanol Treatment On Adh Activitymentioning

confidence: 99%

“…As a consequence of these event, therefore, a greater rate of NADH reoxidation occurs, resulting in a greater rate of production of NAD, which stimulates ethanol oxidation via ADH (75). However, Thurman et al (76) recently noted that an increased activity of the (Na++K+)-stimulated ATPase is probably not involved in the mechanism of the adaptive increase, but diminished rates of glycolysis done.…”

Section: Efct Of Long-term Ethanol Treatment On Adh Activitymentioning

confidence: 99%

“…Approximately 20 to 30% of ethanol metabolism was found to persist even in the presence of either 4-methylpyrazole or pyrazole, potent ADH inhibitors (43,76,81). The pyrazole-insensitive ethanol metabolism, non-ADH pathway, has been attributed to a microsomal ethanol-oxidizing system (MEOS) and/or a peroxidatic reaction of catalase-H202 (4).…”

Section: Efct Of Long-term Ethanol Treatment On Adh Activitymentioning

confidence: 99%

See 1 more Smart Citation

Effect of ethanol administration on alcohol dehydrogenase activity in mouse hepatic cells: ultracytochemical study.

Watabiki

Ishida

Ogawa

1981

Acta Histochem. Cytochem

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The adaptive increase in ethanol metabolism due to pretreatment with ethanol: A rapid phenomenon

Cited by 27 publications

References 9 publications

Modulation of mitochondrial membrane permeability in pathogenesis, autophagy and control of metabolism

Modulation of mitochondrial membrane permeability in pathogenesis, autophagy and control of metabolism

Regulation of mitochondrial function by voltage dependent anion channels in ethanol metabolism and the Warburg effect

Effect of ethanol administration on alcohol dehydrogenase activity in mouse hepatic cells: ultracytochemical study.

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