期刊
AMINO ACIDS
卷 48, 期 2, 页码 549-558出版社
SPRINGER WIEN
DOI: 10.1007/s00726-015-2110-2
关键词
Taurine; Respiratory chain; Palmitate metabolism; Glucose oxidation; ATP production; MELAS
资金
- Uehara Memorial Foundation
- American Heart Association
Taurine is a beta-amino acid found in high concentrations in excitable tissues, including the heart. A significant reduction in myocardial taurine content leads to the development of a unique dilated, atrophic cardiomyopathy. One of the major functions of taurine in the heart is the regulation of the respiratory chain. Hence, we tested the hypothesis that taurine deficiency-mediated defects in respiratory chain function lead to impaired energy metabolism and reduced ATP generation. We found that while the rate of glycolysis was significantly enhanced in the taurine-deficient heart, glucose oxidation was diminished. The major site of reduced glucose oxidation was pyruvate dehydrogenase, an enzyme whose activity is reduced by the increase in the NADH/NAD(+) ratio and by decreased availability of pyruvate for oxidation to acetyl CoA and changes in [Mg2+](i). Also diminished in the taurine-deficient heart was the oxidation of two other precursors of acetyl CoA, endogenous fatty acids and exogenous acetate. In the taurine-deficient heart, impaired citric acid cycle activity decreased both acetate oxidation and endogenous fatty acid oxidation, but reductions in the activity of the mitochondrial transporter, carnitine palmitoyl transferase, appeared to also contribute to the reduction in fatty acid oxidation. These changes diminished the rate of ATP production, causing a decline in the phosphocreatine/ATP ratio, a sign of reduced energy status. The findings support the hypothesis that the taurine-deficient heart is energy starved primarily because of impaired respiratory chain function, an increase in the NADH/NAD(+) ratio and diminished long chain fatty acid uptake by the mitochondria. The results suggest that improved energy metabolism contributes to the beneficial effect of taurine therapy in patients suffering from heart failure.
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