The Role of Amino Acids in the Modulation of Cardiac Metabolism During Ischemia and Heart Failure

Abstract

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.

Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Metabolomic Profile of Heart Failure

“…We had similar findings in our study. The decreased levels of threonine, glycine, serine, and cysteine indicate energy deficiency and mitochondrial dysfunction in HF 48 . The plasma levels of glycerol, linoleate, myristate, and cholesterol, which were reduced in HF patients, may indicate reduced lipid metabolism.…”

Metabolomic profiling analysis reveals chamber-dependent metabolite patterns in the mouse heart

“…Amino acids are involved in a variety of key biochemical and physiological activities. Some of them can be a source of substrate for energy production, such as the TCA cycle (22). Most of the amino acids that can be the source of substrate, such as glutamine, histidine, lysine, arginine, and asparagines, were higher in the ventricles, suggesting that these amino acids can be involved in energy supply in the ventricles, which are likely to have higher energy demands than the atria.…”

“…known to be important energy sources in impaired hearts, although they play a minor role in energy sources under normal conditions (22,30,34). Therefore, they may work as an energy reserve in the ventricles.…”

Metabolic and Clinical Effects of the Supplementation of a Functional Mixture of Amino Acids in Cerebral Hemorrhage

“…Furthermore, the long-term supplementation of the functional amino acid mixture improved cardiac function and remodeling in patients with type 2 diabetes and mild-to-moderate left ventricular dysfunction [7]. The molecular mechanisms responsible for these clinical effects are currently under investigation, but they include modulation of energy and protein metabolism, oxidative stress, and insulin sensitivity [8]. These factors appear to be positively influenced by the ratio among amino acids in the supplement.…”