Exercise and Metabolism

Exercise and prolonged fasting alter metabolic activity. Sprinting demands a quick input of energy. The first energy source for sprinting is the compound creatine phosphate. Like arginine, creatine contains a guanido group. Creatine is a muscle storage system for high‐energy phosphate bonds. The ⁰ for the hydrolysis of creatine phosphate is about 10.3 kcal (43.1 kJ) per mole, which is about 3 kcal per mole greater than the hydrolysis of ATP. The reaction looks like this:

In the standard state, the equilibrium for this reaction lies far to the left; in other words, the reaction is unfavored. However, in the standard state, all the reactants and products are at one molar concentration. In other words, the ratio of ATP to ADP concentrations would be 1. In an actively metabolizing state, the ratio of ATP to ADP is as much as 50 or 100 to 1—this means that the formation of Cr∼P will occur to a reasonable level. Creatine phosphate forms a reservoir for high‐energy phosphate in the same way that water can be pumped upstream to a reservoir and released for use later on.

Anaerobic exercise: sprinting

During sprinting, the following series of events occur:

ATP is depleted as the muscles contract. ADP concentrations rise.
Phosphates are transferred back to ATP from creatine phosphate for further rounds of muscle contraction.
Creatine phosphate stores several times the amount of energy that is in ATP.
Quick ATP synthesis supplies the energy for a few seconds of sprinting.
Anaerobic glycolysis must work next.
Glucose comes from glycogen stores in muscle; it is catabolized to lactate and released into the circulation. As the ATP decreases in the muscle, the enzyme myokinase interconverts the resulting ADP to salvage one ATP out of two ADP.

The ATP can then power another contraction. Eventually, the amount of ATP available approaches a level too low to be bound by myosin in the muscle, even though it is by no means exhausted. The protons (acid) from metabolism cause hemoglobin to release its oxygen more readily, promoting a switch to aerobic metabolism. Lactate and protons from glycolysis may also lead to fatigue and an inability to sustain the level of speed that was possible earlier. In most humans, this seems to occur after a run of about 400 meters, which is why “running quarters” is one of the most unpleasant exercises for any athlete, no matter how well conditioned.

Aerobic metabolism: prolonged exercise

Only a finite amount of glycogen remains available in humans for exercise. The total glycogen plus glucose is about 600 to 700 kcal, even if it is metabolized aerobically. Running consumes this amount of energy in 1.5 to 2 hours. Using fat and/or muscle protein is necessary to keep going. Distance running therefore requires mobilization of fat to supplement glycogen breakdown; this is better done sooner than later in a long run. Competitive runners are dedicated to a variety of nutritional strategies alleged to mobilize fatty reserves. Caffeine inhibits the breakdown of cyclic AMP and therefore contributes to the activation of glycogen phosphorylase; it also acts like epinephrine or glucagon and mobilizes lipids. Carnitine, the carrier of fatty acids into the mitochondrial matrix, is used as a dietary supplement with some success. Finally, distance runners try to increase their stores of muscle glycogen by carbohydrate loading. This is a two‐step procedure. In the first step, a distance runner eats a very low‐carbohydrate diet and exercises vigorously to deplete glycogen stores. Then he or she eats a large amount of carbohydrates, such as bread and pasta, which cause the muscles to store glycogen in greater amount than they would normally store.

Nutritional state

Humans usually eat a few times a day. This means that an individual's normal nutritional status cycles between two states, well‐fed and fasting. Biochemically, the source of glucose, which is far and away the preferred source of energy for the brain, defines these states. During the well‐fed state, the diet supplies glucose and the rest of the energy needed for protein synthesis. Between meals, the breakdown of glycogen and gluconeogenesis from amino acids supplies the glucose requirements. In more advanced cases of starvation, muscle protein is broken down more extensively for gluconeogenesis. In advanced stages of starvation, glucose metabolism is reduced and the brain metabolizes ketone bodies for energy.

The digestion of foodstuffs in and absorption from the intestinecharacterizes the well‐fed state, which lasts for about four hours after a meal. Free amino acids and glucose are absorbed and transported to the liver. Excess energy is converted to fat in the liver and transported, along with dietary fat, to the adipose tissues. The pancreas releases high levels of insulin in response to these events. Insulin signals the liver to convert glucose to glycogen, amino acids to protein, and fat to triglycerides. The adipose tissues synthesize and deposit fats. A deficiency of insulin is a cause of diabetes, characterized by excess levels of blood glucose. In this disease, glucose is not converted into glycogen or fat, so it remains in the circulation.

As the individual enters the fasting state, glycogen is broken down into glucose to supply energy for the tissues. Simultaneously, gluconeogenesis begins as amino acids, lactate, and pyruvate from metabolism are cycled into the formation of glucose. As fats are broken down, the fatty acids supply energy to the peripheral tissues, while the glycerol from breaking down the triacylglycerols is transported to the liver and converted to glucose. Gluconeogenesis becomes more important than glycogen breakdown after about 16 hours of fasting. Gluconeogenesis is maximal after about two days without food, at which time ketone bodies are made from fat and transported to the brain. This transition describes the beginning of starvation, which can last for six to ten weeks before death occurs. During starvation, the body breaks down amino acids for glucose; however, ketone bodies and fat supply most energy requirements. At this time, the body is in negative nitrogen balance, because the amount of nitrogen excreted due to protein breakdown exceeds the nitrogen eaten in food. The small amount of glucose made is supplied to brain, kidney, and red blood cells. The latter two tissues have no alternative energy sources; the brain uses both ketone bodies and glucose. When fat is gone, the only sources of energy available are amino acids from muscle. The carbon skeletons are metabolized, and the nitrogen is excreted. This situation cannot continue for very long. Eventually, the kidneys fail, or the heart muscle is broken down, and the individual dies.

Biochemistry II