Effects of acute ethanol administration on rat liver 5-aminolaevulinate synthase activity

Abstract

1. Liver 5-aminolaevulinate (ALA) synthase activity of 24 h-starved rats is maximally increased at 4 h after intraperitoneal administration of a 1.6 g/kg body wt. dose of ethanol. Larger doses cause a dose-dependent decrease in the extent of this stimulation, exhibiting a reciprocal relationship with an elevation of hepatic haem concentration, as suggested by the simultaneous increase in the haem saturation of tryptophan pyrrolase. 2. ALA synthase induction by ethanol is abolished if the above increase in pyrrolase saturation with haem is enhanced by theophylline, but is potentiated when the increase in the haem saturation is inhibited by anti-lipolytic agents. 3. ALA synthase induction by ethanol is also inhibited by inhibitors of alcohol dehydrogenase and aldehyde dehydrogenase. Acetaldehyde and acetate are, however, not responsible; they both decrease ALA synthase activity and increase the haem saturation of tryptophan pyrrolase. These latter effects of acetaldehyde are not mediated by acetate. 4. ALA synthase activity is also stimulated by succinate, which, however, also increases the haem saturation of tryptophan pyrrolase. 5. Ethanol does not influence the rate of ALA synthase degradation. 6. It is suggested that ethanol increases rat liver ALA synthase activity as a result of its own metabolism by the alcohol dehydrogenase-dependent pathway by a mechanism not involving decreased degradation of the former enzyme or the participation of the metabolites acetaldehyde and acetate.

Tissue‐specific expression of ALA synthase‐1 and heme oxygenase‐1 and their expression in livers of rats chronically exposed to ethanol

“…Our findings agree well with the previously published results in which chronic ethanol administration increased hepatic ALAS1 enzyme activities by two-to three-fold compared with those pair-fed controls [14][15][16]. Considering that the intra-mitochondrial mature ALAS1 is the functional form, and 2.3-fold increase in the levels of the mature protein after ethanol treatment provides a rationale for the ethanol induced increase (two-to three-fold) in ALAS1 enzyme activities observed by other investigators [14][15][16]. In this same experiment, HO-1 protein levels were nearly undetectable (data not shown), suggesting ethanol had no effect on HO-1 protein levels.…”

“…Earlier work showed that ethanol administration increases hepatic ALAS1 enzyme activities in rats [14][15][16]. Some have proposed that this effect is secondary to depletion of a heme regulatory pool, which is depleted during increased formation of cytochrome(s) P-450 [15].…”

Acute Hepatic Porphyrias: Review and Recent Progress

“…Medications including but not limited to estrogens, progestogens, barbiturates, sulfonamides, and other inducers of cytochromes P450 and ALAS‐1 should be avoided, and websites with recommendations based on existing evidence should be consulted before starting any new medications. Patients should avoid smoking, including marijuana, and avoid heavy alcohol intake, as each can induce cytochromes P450, and alcohol is known to induce hepatic ALAS‐1 . We recommend in general that men should adhere to no more than two, and women to no more than one, drink per day.…”

“…Patients should avoid smoking, including marijuana, and avoid heavy alcohol intake, as each can induce cytochromes P450, and alcohol is known to induce hepatic ALAS-1. (17) We recommend in general that men should adhere to no more than two, and women to no more than one, drink per day.…”