Impaired energy metabolism in rat myocardium during phosphate depletion

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Abstract
The effects of phosphate depletion (PD) of 4-, 8- and 12-wk duration on myocardial energy metabolism were studied in rats fed a phosphate-deficient diet and compared with rats pair-fed a normal phosphate diet. Myocardial biopsies were examined for high-energy phosphate bonds. PD causes a significant reduction in myocardial concentration of inorganic phosphorus at 4 wk of PD and creatine phosphate at 8 wk of PD, while adenine nucleotides were significantly reduced only after 12 wk of PD. The changes in cellular inorganic phosphorus and creatine phosphate displayed a significant correlation with serum P levels. Mitochondrial respiration was impaired early in PD. Total cellular, mitochondrial and myofibrillar creatine kinase activities were significantly reduced at 4 wk of PD and fell further at 8 and 12 wk. Chronic PD is associated with reduced mitochondrial capacity to produce ATP, impaired transport via the creatine phosphate shuttle and reduced myofibrillar ability to utilize ATP. All steps of myocardial energetics are impaired in PD and provide the molecular basis for the altered myocardial function seen in PD.