Ethanol, acetaldehyde, and myocardial protein synthesis.
The cause of alcoholic myocardiopathy is unknown. The effects of acute exposure to ethanol or its metabolite acetaldehyde on protein synthesis in working, intact, guinea pig hearts in vitro were studied utilizing lysine-(14)C perfusion. Ethanol at 250 mg/100 ml, a level sufficient to markedly inhibit hepatic production of albumin, did not alter cardiac function, the equilibration of the intracellular free lysine pool in either ventricle, or the incorporation of lysine-(14)C into protein. Thus, in controls and ethanol-perfused hearts, the incorporation of lysine in 3 hr was 44.1+/-1.5 and 42.8+/-1.2 mumoles lysine/g protein N for the right ventricles and 25.6+/-1.0 and 24.3+/-0.8 for the left ventricles, respectively. Only at lethal levels, 1500 mg/100 ml ethanol, was protein synthesis depressed. Acetaldehyde 3.5 mg/100 ml (0.8 mM) effected a markedly positive chronotropic and inotropic effect on the perfused heart and slightly depressed equilibration of the intracellular free lysine pool. However, determinations of protein incorporation of lysine-(14)C based on intracellular lysine-(14)C specific activities showed a significant decrease from control right and left ventricle values, to 27.1+/-2.8 and 14.9+/-1.9. Propanalol, which abolished the chronotropic effect, did not prevent the inhibition of protein synthesis. The studies suggest that acetaldehyde, which inhibits cardiac protein synthesis in vitro, may play a role in alcoholic myocardiopathy by interfering with normal myocardial protein synthesis.
D000079:Acetaldehyde / Q000096:biosynthesis / Q000494:pharmacology*; D000418:Albumins / Q000378:metabolism; D000437:Alcoholism / Q000150:complications; D000818:Animals; D002247:Carbon Isotopes; D003864:Depression, Chemical; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000209:etiology; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis*; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology
D000418:Albumins; D002247:Carbon Isotopes; D009124:Muscle Proteins; D000431:Ethanol; D011433:Propranolol; D000079:Acetaldehyde; D008239:Lysine