Effects of chronic ethanol treatment upon rat liver mitochondria

Kinetics and control of oxidative phosphorylation in rat liver mitochondria after chronic ethanol feeding

“…In agreement with previous studies that reported a decline in electron transport components [5,10,[22][23][24][25][26], the rate of generation of ∆p (the respiratory subsystem) with different substrates was inhibited after 2 months of ethanol consumption. With NAD + -dependent substrates and TMPD\ascorbate a significant suppression of the respiratory subsystem was observed at all values of the mitochondrial membrane potential examined, with more pronounced inhibition in State 3 than State 4.…”

“…The results presented in Table 1 demonstrate that 2 months of chronic alcohol treatment diminished the activities of the bc " complex, cytochrome oxidase and ATPase in rat liver mitochondria by 41p5 %, 40p6 % and 36p4 % respectively (Table 1). These data are consistent with previous studies [5,10,[22][23][24][25][26]. The alterations in the component activities bring about the differential responses of each block of reactions R, L and P to changes in ∆Ψ.…”

“…The most prominent site of ethanol-induced mitochondrial changes is the liver. Early studies [5,6] established that liver mitochondria isolated from rats fed an ethanol-containing diet for 3-5 weeks exhibited a decrease in NAD-linked respiration, both under conditions of active respiration (State 3, defined as the mitochondrial state in which ADP supply is saturating and excess substrate and P i are available) and in uncoupled mitochondria. Subsequent studies (reviewed in [2]) demonstrated that these effects had their origin in a decrease in the activity of select components of the oxidative phosphorylation machinery, notably NADH dehydrogenase, cytochrome b, cytochrome oxidase and ATP synthase.…”

Multiple biochemical effects in the pathogenesis of alcoholic fatty liver

“…Changes in the activity of the mitochondrial respiratory chain could be responsible for both diminished b-oxidation and citric acid cycle activities. Many studies have found diminished respiratory chain activity in alcoholic fatty liver in both rat [33,34] and baboon [35], and these have been attributed to lowered transcription of mitochondrially encoded subunits of respiratory chain proteins [36]. The only human study of the activity of respiratory chain complexes in alcoholic fatty liver, however, found unchanged activity of complex IV, which is partially mitochondrially encoded, when compared with complex II, which is entirely nuclearly encoded [37], suggesting that rat studies may not necessarily be relevant to human alcoholic fatty liver.…”

“…However, because of continued alcohol intake, other factors become operative, which lead to continued accumulation of triacylglycerol and hence steatosis. In this second phase, there are increases in phosphatidate phosphohydrolase and diacylglycerol acyltransferase activities [15,16], increased fatty acid binding protein levels [19], decreased VLDL secretion [8] and decreased b-oxidation resulting from mitochondrial alterations [33,35,36,38]. In addition, heterozygotes for genetic conditions that would lead to steatosis, such as trifunctional protein deficiency in which heterozygote effects have been observed [43,44], could be predisposed to the development of alcoholic fatty liver.…”