Skeletal muscle fuels

Hardie DG, Sakamoto K (2006) AMPK a key sensor of fuel and energy status in skeletal muscle. Physiology (Bethesda) 21 48-60... 

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. 

In adipose tissue, the effect of the decrease in insulin and increase in glucagon results in inhibition of lipo-genesis, inactivation of lipoprotein lipase, and activation of hormone-sensitive lipase (Chapter 25). This leads to release of increased amounts of glycerol (a substrate for gluconeogenesis in the liver) and free fatty acids, which are used by skeletal muscle and liver as their preferred metabolic fuels, so sparing glucose. 

The entry rate of glucose into red blood cells is far greater than would be calculated for simple diffusion. Rather, it is an example of facilitated diffiision (Chapter 41). The specific protein involved in this process is called the glucose transporter or glucose permease. Some of its properties are summarized in Table 52-3-The process of entry of glucose into red blood cells is of major importance because it is the major fuel supply for these cells. About seven different but related glucose transporters have been isolated from various tissues unlike the red cell transporter, some of these are insidin-dependent (eg, in muscle and adipose tissue). There is considerable interest in the latter types of transporter because defects in their recruitment from intracellular sites to the surface of skeletal muscle cells may help explain the insulin resistance displayed by patients with type 2 diabetes mellitus. 

The major fuels of skeletal muscle are glucose and fatty acids. Because of the enormous bulk, skeletal muscle is the body s major consumer of fuel. After a meal, under the influence of insulin, skeletal muscle takes up glucose to replenish glycogen stores and amino acids that are used for protein synthesis. Both excess glucose and amino acids can also be oxidized for energy. 

The primary fuel used to support muscle contraction depends on the magnitude and duration of exercise as well as the major fibers involved. Skeletal muscle has stores of both glycogen and some triglycerides. Blood glucose and free fatty acids also may be used. 

The observation of possibly increased IMCL levels in highly trained athletes led to a second focus of research in the field of sports medicine. Besides carbohydrates, lipids are the major fuel of skeletal muscle during work and rest. A variety of questions have to be answered. It was examined, whether exercise of various intensities alters IMCL levels, whether those changes depend on the duration of exercise, and finally, how IMCL are replenished during post-exercise recovery. 

Ketone bodies are oxidised by most aerobic tissues including skeletal muscle, heart, kidney, lung, intestine and brain. Since the last two cannot oxidise fatty acids, their ability to oxidise ketone bodies is very important, because they provide another fuel in addition to, or as an alternative to, glucose. Hence, they can be used to replace some of the glucose to maintain the blood glucose concentration (e.g. in prolonged starvation or hypoglycaemia). 

The major role of skeletal muscle is movement, which is described and discussed in Chapter 13). Nevertheless, since muscle comprises 40% of the body it is large enough to play a part in control of the blood concentrations of the major fuels glucose, fatty acids, triacylglycerol and some amino acids. Skeletal muscle contains the largest quantity of protein in the body, which is used as a source of amino acids under various conditions (e.g. starvation, trauma, cancer see above). It plays an important part in the metabolism, in particular, of branched-chain amino acids, glutamine and alanine, which are important in the overall metabolism of amino acids in the body (discussed below). 

As hormone-sensitive lipase hydrolyzes triacylglyc-erol in adipocytes, the fatty acids thus released (free fatty acids, FFA) pass from the adipocyte into the blood, where they bind to the blood protein serum albumin. This protein (Mv 66,000), which makes up about half of the total serum protein, noncovalently binds as many as 10 fatty acids per protein monomer. Bound to this soluble protein, the otherwise insoluble fatty acids are carried to tissues such as skeletal muscle, heart, and renal cortex. In these target tissues, fatty acids dissociate from albumin and are moved by plasma membrane transporters into cells to serve as fuel. 

Chylomicrons deliver tiiacylglycerols to tissues, where lipoprotein lipase releases free fatty acids for entry into cells. Triacylglycerols stored in adipose tissue are mobilized by a hormone-sensitive triacylglycerol lipase. The released fatty acids bind to serum albumin and are carried in the blood to the heart, skeletal muscle, and other tissues that use fatty acids for fuel. 

Under all these metabolic conditions, amino acids lose their amino groups to form a-keto acids, the carbon skeletons of amino acids. The a-keto acids undergo oxidation to C02 and H20 or, often more importantly, provide three- and four-carbon units that can be converted by gluconeogenesis into glucose, the fuel for brain, skeletal muscle, and other tissues. 

When fuel demand rises, lipases in adipocytes hydrolyze stored TAGs to release free fatty acids, which can travel in the bloodstream to skeletal muscles and the heart. The release of fatty acids from adipocytes is... 

Skeletal muscle can use free fatty acids, ketone bodies, or glucose as fuel, depending on the degree of muscular activity (Fig. 23-17). In resting muscle, the primary fuels are free fatty acids from adipose tissue and... 

The main stores of glycogen in the body are found in skeletal muscle, where they serve as a fuel reserve for the synthesis of ATP during muscle contraction, and in the liver, where glycogen is used to maintain the blood glucose concentration, particularly during the early stages of a fast. 

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