Wasting and the substrate-to-energy controlled pathway: a role for insulin resistance and amino acids

Amino acids contained in proteins can be transformed either in glucose precursors or in acetate, the end product of free fatty acid (FFA) oxidation. The dynamics of glucose, FFA, and amino acid competition for entry into the citric acid cycle (tricarboxylic acid [TCA] cycle) are very complex and not fully understood. Conditions where glucose is insufficiently driven to full oxidation are characterized by lowest efficiency in energy production per mole of oxygen consumed. Moreover, acetate provided by oxidation of FFA increases consumption of amino acids as precursors of the oxaloacetate required for condensation with acetate and for maintenance of citrate synthesis. Increased consumption of amino acids in the TCA cycle, if not matched by adequate intake, leads to muscular wasting and cachexia. Therefore, amino acid needs are very complex, and their intake must provide a balanced ratio of glucogenic and ketogenic precursors suitable to trigger entry of glucose to full oxidation and blunt the level of FFA utilization. Optimization of substrate entry into energy production must also be coupled with sufficient availability of amino acids in ratios suitable for maintaining protein synthesis, inhibiting the catabolic drive, and promoting integrity of cellular proteic structures. Alimentary proteins have a content of amino acids that is far from the stoichiometric ratios of essential amino acids required by humans. An amino acid formulation suitable to match energy needs, control carbohydrate and lipid flow into the TCA cycle, and promote protein synthesis in contracting cells is detailed in this article.