Marazzi Giuseppe, Rosanio Salvatore, Caminiti Giuseppe, Dioguardi Francesco Saverio, Mercuro Giuseppe
IRCCS San Raffaele Centre for Clinical and Basic Research, Department of Medical Sciences, Via della Pisana 235, 00163 Rome, Italy.
Curr Pharm Des. 2008;14(25):2592-604. doi: 10.2174/138161208786071227.
During ischemia and heart failure, myocardial cells suffer for chronic energy starvation resulting in metabolic and contractile dysfunction. In normal conditions fatty acids, glucose, and lactate are the principal oxidative fuels in myocardium, while amino acids serve a minor role as an oxidative fuel. However, in pathological conditions, myocardial uptake of several amino acids increases significantly as a consequence of a metabolic remodelling. Amino acids are involved in a variety of key biochemical and physiological activities, that counteract the deleterious cellular effects of reduced oxygen availability. Several amino acids are a direct source of substrate for energy production, and they modulate the activity of some enzymes involved in the glucose metabolism. They increase contractile performance both in isolated animal and human myocardium. Furthermore, amino acids improve the oxidative stress counteracting the action of radical oxygen species, being either precursors of glutathione synthesis, or of substrate of nitric oxide biosynthesis; they act on endothelial function and increase protein synthetic efficiency of myocardial cells by regulating gene expression and modulating hormonal activity. An amount of studies have demonstrated that amino acids administration, on patients with ischemic heart disease and heart failure, can improve several clinical endpoints. Here, we present an overview of the principal effects of the most experienced amino acids and of amino acid derivatives on ischemia and heart failure.
在缺血和心力衰竭期间，心肌细胞遭受慢性能量饥饿，导致代谢和收缩功能障碍。在正常情况下，脂肪酸、葡萄糖和乳酸是心肌的主要氧化燃料，而氨基酸作为氧化燃料的作用较小。然而，在病理状态下，由于代谢重塑，心肌对几种氨基酸的摄取显著增加。氨基酸参与多种关键的生化和生理活动，可抵消氧供应减少对细胞的有害影响。几种氨基酸是能量产生的直接底物来源，它们调节参与葡萄糖代谢的一些酶的活性。它们在离体动物和人心肌中均能增强收缩性能。此外，氨基酸可改善氧化应激，对抗活性氧的作用，它们既是谷胱甘肽合成的前体，也是一氧化氮生物合成的底物；它们作用于内皮功能，并通过调节基因表达和调节激素活性来提高心肌细胞的蛋白质合成效率。大量研究表明，对缺血性心脏病和心力衰竭患者给予氨基酸可改善多个临床终点。在此，我们概述了最常用的氨基酸及其衍生物对缺血和心力衰竭的主要作用。
