title: Energy metabolism in heart failure and remodelling.
abstract: Myocytes of the failing heart undergo impressive metabolic remodelling. The time line for changes in the pathways for ATP synthesis in compensated hypertrophy is: flux through the creatine kinase (CK) reaction falls as both creatine concentration ([Cr]) and CK activity fall; increases in [ADP] and [AMP] lead to increases in glucose uptake and utilization; fatty acid oxidation either remains the same or decreases. In uncompensated hypertrophy and in other forms of heart failure, CK flux and fatty acid oxidation are both lower; any increases in glucose uptake and utilization are not sufficient to compensate for overall decreases in the capacity for ATP supply and [ATP] falls. Metabolic remodelling is under transcriptional and post-transcriptional control. The lower metabolic reserve of the failing heart contributes to impaired contractile reserve.
authors.affiliation: NMR Laboratory for Physiological Chemistry, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Room 247, Boston, MA 02115, USA. jingwall@rics.bwh.harvard.edu
authors.forename: Joanne S
authors.initials: JS
authors.lastname: Ingwall
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000378:metabolism / Q000503:physiopathology; D003402:Creatine Kinase / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics; D006019:Glycolysis; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010641:Phenotype; D010725:Phosphocreatine / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013997:Time Factors; D014158:Transcription, Genetic; D020257:Ventricular Remodeling
chemical_list: D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D000263:Adenylate Kinase