Dysregulation of skeletal muscle protein metabolism by alcohol

Am J Physiol Endocrinol Metab. 2015 May 1;308(9):E699-712. doi: 10.1152/ajpendo.00006.2015. Epub 2015 Mar 10.


Alcohol abuse, either by acute intoxication or prolonged excessive consumption, leads to pathological changes in many organs and tissues including skeletal muscle. As muscle protein serves not only a contractile function but also as a metabolic reserve for amino acids, which are used to support the energy needs of other tissues, its content is tightly regulated and dynamic. This review focuses on the etiology by which alcohol perturbs skeletal muscle protein balance and thereby over time produces muscle wasting and weakness. The preponderance of data suggest that alcohol primarily impairs global protein synthesis, under basal conditions as well as in response to several anabolic stimuli including growth factors, nutrients, and muscle contraction. This inhibitory effect of alcohol is mediated, at least in part, by a reduction in mTOR kinase activity via a mechanism that remains poorly defined but likely involves altered protein-protein interactions within mTOR complex 1. Furthermore, alcohol can exacerbate the decrement in mTOR and/or muscle protein synthesis present in other catabolic states. In contrast, alcohol-induced changes in muscle protein degradation, either global or via specific modulation of the ubiquitin-proteasome or autophagy pathways, are relatively inconsistent and may be model dependent. Herein, changes produced by acute intoxication versus chronic ingestion are contrasted in relation to skeletal muscle metabolism, and limitations as well as opportunities for future research are discussed. As the proportion of more economically developed countries ages and chronic illness becomes more prevalent, a better understanding of the etiology of biomedical consequences of alcohol use disorders is warranted.

Keywords: alcohol use disorder; ethanol; protein synthesis; proteolysis; skeletal muscle.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alcohol Drinking / adverse effects
  • Alcohol Drinking / metabolism
  • Alcoholic Intoxication / metabolism
  • Animals
  • Ethanol / pharmacology*
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / metabolism
  • Muscle Proteins / drug effects*
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscular Atrophy / etiology
  • Muscular Atrophy / metabolism
  • Protein Biosynthesis / drug effects*
  • TOR Serine-Threonine Kinases / metabolism


  • Multiprotein Complexes
  • Muscle Proteins
  • Ethanol
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases