Energy metabolism in heart failure and remodelling.
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.
Ingwall
Joanne S
JS
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
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
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D000263:Adenylate Kinase