Impaired energy metabolism of the taurine-deficient heart

Abstract

Taurine is a β-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.

Mitochondrial defects associated with β-alanine toxicity: relevance to hyper-beta-alaninemia

“…We recently found that rats fed β-alanine exhibit impaired mitochondrial energy metabolism and cardiac weakness [10], effects consistent with the reports of β-alanine-mediated hypotonia. In the present study, we examine the effect of β-alanine exposure on isolated cardiomyocytes and fibroblasts, which are the two major cell types of the heart.…”

“…We have recently shown that hearts of β-alanine-treated rats exhibit reduced contractile function, an effect related in part to impaired mitochondrial energy metabolism [10]. In the present study, we found that the major site of β-alanine action is complex I of the respiratory chain.…”

“…It has been suggested that taurine-mediated alterations in citric acid cycle flux, ATP production and mitochondrial ROS generation relate to the posttranslational conversion of tRNA Leu(UUR) to 5-taurinomethyluridine-tRNA Leu(UUR) [10, 18, 19]. The uridine base modified by taurine is located in the wobble position of the anticodon (AAU) of tRNA Leu(UUR) .…”

“…In the present study, we found that the major site of β-alanine action is complex I of the respiratory chain. By reducing flux through complex I, β-alanine treatment decreases both oxygen consumption and ATP generation of the β-alanine-treated heart [10]. Moreover, the similarity between the actions of rotenone and those of β-alanine [21] implies that β-alanine-mediated reductions in complex I activity also cause a diversion of electrons from complex I to the acceptor oxygen, forming in the process superoxide.…”

Taurine: A Regulator of Cellular Redox Homeostasis and Skeletal Muscle Function

“…Furthermore, an increased lactate/pyruvate ratio and decreased muscular ATP (adenosine triphosphate) production indicate a poor energy supply in Taut (–/–) compared to wild‐type mice . Likewise, decreased markers of fatty acid oxidation and tricarboxylic acid (TCA) cycle activity but increased markers of glycolysis were observed in taurine‐deficient heart muscle. These results indicate that taurine‐depleted muscles favor glucose as an anaerobic cellular energy supply, while mitochondrial bioenergetics (fatty acid oxidation, the TCA cycle, and oxidative phosphorylation [OXPHOS]) are diminished.…”