Increased Adenine Nucleotide Degradation in Skeletal Muscle Atrophy

• Published in: International journal of molecular sciences Vol. 21; no. 1; p. 88
• Main Authors: Miller, Spencer G, Hafen, Paul S, Brault, Jeffrey J
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.12.2019; MDPI
• Subjects: Adenine; Adenine Nucleotides - metabolism; Adenosine; Adenosine triphosphate; Animals; Atrophy; Cancer; Chemical energy; Chronic illnesses; Chronic obstructive pulmonary disease; Congestive heart failure; Coronary artery disease; Cytokines; Degradation products; Denervation; Diabetes mellitus; Disease; Energy; Enzymes; Humans; Hypoxanthine; Intracellular signalling; Kidney diseases; Kinases; Metabolism; Muscle contraction; Muscle, Skeletal - growth & development; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscles; Muscular Disorders, Atrophic - metabolism; Muscular dystrophy; Musculoskeletal system; Nucleotides; Physiology; Protein metabolism; Protein synthesis; Protein turnover; Proteins; Quality of life; Renal failure; Review; RNA polymerase; Sarcopenia; Sarcopenia - metabolism; Sepsis; Skeletal muscle; Solubilization; Uric acid; Xanthines - metabolism; adenine nucleotide; AMP; cachexia; muscle; atrophy; ATP; uric acid; energetics; sarcopenia
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21010088

Adenine nucleotides (AdNs: ATP, ADP, AMP) are essential biological compounds that facilitate many necessary cellular processes by providing chemical energy, mediating intracellular signaling, and regulating protein metabolism and solubilization. A dramatic reduction in total AdNs is observed in atrophic skeletal muscle across numerous disease states and conditions, such as cancer, diabetes, chronic kidney disease, heart failure, COPD, sepsis, muscular dystrophy, denervation, disuse, and sarcopenia. The reduced AdNs in atrophic skeletal muscle are accompanied by increased expression/activities of AdN degrading enzymes and the accumulation of degradation products (IMP, hypoxanthine, xanthine, uric acid), suggesting that the lower AdN content is largely the result of increased nucleotide degradation. Furthermore, this characteristic decrease of AdNs suggests that increased nucleotide degradation contributes to the general pathophysiology of skeletal muscle atrophy. In view of the numerous energetic, and non-energetic, roles of AdNs in skeletal muscle, investigations into the physiological consequences of AdN degradation may provide valuable insight into the mechanisms of muscle atrophy.