Muscle amino acid utilization

Skeletal muscle utilizes glucose as a fuel, forming both lactate and CO2. It stores glycogen as a fuel for its use in muscular contraction and synthesizes muscle protein from plasma amino acids. Muscle accounts for approximately 50% of body mass and consequently represents a considerable store of protein that can be drawn upon to supply amino acids for gluconeogenesis in starvation. 

This results in the extrusion of three positive charges for every two that enter the cell, resulting in a transmembrane potential of 50-70 mV, and has enormous physiological significance. More than one-third of the ATP utilized by resting mammalian cells is used to maintain the intracellular Na+-K+ gradient (in nerve cells this can rise up to 70%), which controls cell volume, allows neurons and muscle cells to be electrically excitable, and also drives the active transport of sugars and amino acids (see later). 

In a muscle at rest, most of the 2-oxo acids produced from transamination of branched chain amino acids are transported to the liver and become subject to oxidation in reactions catalysed by branched-chain 2-oxo acid dehydrogenase complex. During periods of exercise, however, the skeletal muscle itself is able to utilize the oxo-acids by conversion into either acetyl-CoA (leucine and isoleucine) or succinyl-CoA (valine and isoleucine). 

In mammals, muscle breakdown or excess protein intake results in an imbalance between the fates of the carbon chains and the amino nitrogen. Unlike fat (lipid storage) or glycogen (carbohydrate storage), excess amino acids are not stored in polymeric form for later utilization. The carbon chains of amino acids are generally metabolized into tricarboxylic acid (TCA) cycle intermediates, although it is also possible to make ketone bodies such as acetoacetate from some. Conversion to TCA intermediates is easy to see in some instances. For example, alanine is directly transaminated to pyruvate. 

Unlike the salmon and invertebrate models above, in which amino acids can be utilized (especially if and when lipids become depleted), in most situations in mammals, muscle work displays a minimal dependence upon proteins and amino acids. For most species, this has... 

Carnitine biosynthesis utilizes the essential amino acid lysine, with terminal methyl groups donated by S-adenosylmethionine. Only lysine incorporated into proteins is a substrate for the methylation reaction. In humans, the final reaction in the biosynthetic pathway, catalyzed by a cytosolic hydroxylase, occurs in liver and kidney but not in cardiac or skeletal muscle. The carnitine requirement of these tissues is met by carnitine transported to them via the plasma... 

Figure 32-3. Schematic representation of fuel mobilization during fasting. Catabolism of muscle proteins provides alanine for gluconeogenesis and glutamine for utilization by the gut and kidney, while branched chain amino acids are primarily oxidized within the muscle. Breakdown of adipocyte triacylglycerols provides glycerol and free fatty acids (not shown) the free fatty acids provide fuel for liver, muscle and most other peripheral tissues. The liver utilizes both alanine and glycerol to synthesize glucose which is required for the brain and for red blood cells (not shown). Adapted from Besser and Thirner (2002).

Insulin is synthesized in the B- (or p-) cells of the pancreatic islets of Langerhans. It is a protein (MW 5800) consisting of two peptide chains linked by two disulfide bridges the A chain has 21 and the B chain 30 amino acids. Upon ingestion of carbohydrates, insulin is released into the blood and promotes uptake and utilization of glucose in specific organs, namely, the heart, adipose tissue, and skeletal muscle. 

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