Metabolic and genetic regulation of cardiac energy substrate preference
Comparative Biochemistry and Physiology. Part A: Molecular & Integrative Physiology , Volume 146 - Issue 1 p. 26- 39
Proper heart function relies on high efficiency of energy conversion. Mitochondrial oxygen-dependent processes transfer most of the chemical energy from metabolic substrates into ATP. Healthy myocardium uses mainly fatty acids as its major energy source, with little contribution of glucose. However, lactate, ketone bodies, amino acids or even acetate can be oxidized under certain circumstances. A complex interplay exists between various substrates responding to energy needs and substrate availability. The relative substrate concentration is the prime factor defining preference and utilization rate. Allosteric enzyme regulation and protein phosphorylation cascades, partially controlled by hormones such as insulin, modulate the concentration effect; together they provide short-term adjustments of cardiac energy metabolism. The expression of metabolic machinery genes is also dynamically regulated in response to developmental and (patho)physiological conditions, leading to long-term adjustments. Specific nuclear receptor transcription factors and co-activators regulate the expression of these genes. These include peroxisome proliferator-activated receptors and their nuclear receptor co-activator, estrogen-related receptor and hypoxia-inducible transcription factor 1. Increasing glucose and reducing fatty acid oxidation by metabolic regulation is already a target for effective drugs used in ischemic heart disease and heart failure. Interaction with genetic factors that control energy metabolism could provide even more powerful pharmacological tools.
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|Comparative Biochemistry and Physiology. Part A: Molecular & Integrative Physiology|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Kodde, I.F, van der Stok, J, Smolenski, R.T, & de Jong, J.W. (2007). Metabolic and genetic regulation of cardiac energy substrate preference. Comparative Biochemistry and Physiology. Part A: Molecular & Integrative Physiology (Vol. 146, pp. 26–39). doi:10.1016/j.cbpa.2006.09.014