Selection of fuels for muscle contraction

Only a very small amount of ATP is apparently consumed (and the fall is accounted for by increased ADP). However, a considerable amount of creatine phosphate is consumed (and again the difference is accounted for by increased creatine).

Muscle contraction actually uses a large amount of ATP, which is required immediately. However, there is a significant time lag before the rate of oxidation of metabolic fuels increases to supply ATP. Remember that the total body pool of ATP is very small, but turns over rapidly.

Creatine phosphate acts as an intermediate store of phosphate to rephosphorylate ADP to ATP until metabolic activity increases in response to increased demand for muscle contraction.

This means that the concentration of ATP remains more or less constant, but creatine phosphate is depleted. After the muscle contraction ceases, or when the rate of oxidation of metabolic fuels has increased sufficiently, creatine will be rephosphorylated to creatine phosphate.

Creatine phosphate also acts to shuttle phosphate from the sites of ATP formation (cytosol from glycolysis and mitochondria) to the sites in the cell where it is required for muscle contraction.

Creatinine is formed by non-enzymic cyclisation of creatine or creatine phosphate; it is a metabolically useless product, and is excreted in the urine.

A 70 kg man excretes approximately 16 mmol of creatinine per day; a 70 kg woman approximately 10 mmol / day.

Creatinine formation depends on total creatine content of the body, mainly in muscle; higher creatinine excretion reflects high proportion of muscle in males.

Urine volume, and hence concentration of metabolites, is highly variable; creatinine excretion is reasonably constant from day to day.

Any condition leading to net loss of muscle. This may be muscle atrophy in disease or as a result of prolonged bed rest, or may be the normal loss of myometrium in the female menstrual cycle.

Experiment 2: Glucose utilisation by muscle

Fasting dogs was anaesthetised and the femoral artery and popliteal vein were cannulated to permit measurement of arterio-venous differences across the gastrocnemius-plantaris muscle group, at rest and after electrical stimulation to twitch 1 or 5 times per second, for 30 minutes.

The table shows glucose and oxygen uptake into the muscle, and lactate output from the muscle under these conditions.

A muscle biopsy sample was taken from both the stimulated and unstimulated leg for measurement of glycogen (µmol glucose equivalent /g muscle).

From data reported by Chaplet CK & Stainsby WN (1968). Carbohydrate metabolism in contracting dog skeletal muscle in situ. American Journal of Physiology 215: 995-1004.

At rest muscle is relatively anaerobic, and produces a great deal of lactate. In response to stimulation to twitch there is an increase in perfusion of the muscle, so that at 1 twitch /sec there is considerably more oxygen uptake and relatively little lactate output - the muscle is now metabolising mainly aerobically. There is little depletion of glycogen compared with the unstimulated muscle; most of the ATP is being provided by metabolism of glucose taken up from the bloodstream.

At the higher rate of twitching, although there is a further increase in oxygen uptake, there is also an increase in lactate output. Fast twitching requires a considerable amount of anaerobic glycolysis because the rate of oxygen uptake is inadequate to meet the demand for ATP.

The maximum possible ratio of lactate : glucose is 2. (each mol of glucose yields 2 mol of lactate in glycolysis). However, at rest the results show a lactate output : glucose uptake ratio of 4.6, and at 5 twitches /sec the ration is 2.3.

The source of this lactate must be muscle glycogen - this is confirmed by the small table showing depletion of glycogen at the fast twitch rate.

Experiment 3: Glucose and fat utilisation in exercise over time

The graphs on the right show the rate of disappearance of plasma glucose (left) and non-esterified fatty acids (right) in two separate experiments involving a student walking at moderate speed on a treadmill.

From data cited by Martin WH & Klein S (1998) Use of endogenous carbohydrate and fat as fuels during exercise. Proceedings of the Nutrition Society 57: 49-54

In the experiment in which glucose disappearance was measured, muscle glycogen was also measured by taking a muscle biopsy before and after the exercise; it fell from 111 mmol /kg to 39 mmol /kg during the 105 minutes of exercise.

The graph on the left shows that as exercise continues, so the rate of glucose utilisation increases, as the muscle glycogen becomes depleted. Unfortunately, the authors did not report the rate of glucose utilisation after 100 min, but we can assume that it levelled off and then fell.

Initially little fatty acid is used, then as the exercise continues, the rate of fatty acid oxidation increases. After the time we assume that glycogen reserves are more or less depleted, and the rate of glucose utilisation has fallen, so the rate of fatty acid utilisation increases sharply.

The simple answer is that initially glucose provides the main fuel for muscle, then as exercise continues, so fatty acids become more important as muscle glycogen and available plasma glucose become depleted.

Experiment 4: Carbohydrate and fat utilisation in exercise at different levels of intensity

A 70 kg male student walked on a treadmill at different speeds for 30 minutes each time. He was wearing a respirometer, and his oxygen consumption and carbon dioxide production were measured.

From the figures for oxygen consumption and carbon dioxide production in the table below, calculate:

• his energy expenditure at each speed (as kJ /30 min)
• the Physical Activity Ratio at each speed (a multiple of his Basal Metabolic Rate, which you can assume to be his energy expenditure at rest
• his RQ (respiratory quotient, the ratio of carbon dioxide produced / oxygen consumed) at each speed
• the percentage of energy derived form carbohydrate and fat at each speed (assuming that he is metabolising only fat and carbohydrate)
• the amount of fat (in grams) that he metabolises at each speed

Energy yield, oxygen consumption and carbon dioxide production in the metabolism of metabolic fuels. To first approximation you can use a figure of 20 kJ /L oxygen consumed.

percentage of energy derived from carbohydrate = ((RQ - 0.707) / (1 - 0.707)) x 100

oxygen consumption and carbon dioxide production during 30 min exercise on a treadmill at different speeds

Click here to download a printable version of this table

At modest rates of exercise, fat provides that main fuel for muscle. As the intensity of exercise increases, so fat provides a lower percentage of fuel, and carbohydrate becomes more important. This reflects both the limited capacity for oxygen uptake at high intensity of exercise (fat oxidation is strictly aerobic) and also the limited capacity for fatty acid beta-oxidation in muscle (remember that in prolonged fasting muscle needs ketone bodies because it cannot oxidise enough fatty acids to meet its energy needs).

This decreasing proportion of energy from fat with increasing intensity of exercise has implications for exercise as part of weight reduction – obviously sustained moderate exercise is going to use a greater proportion of fat than shorter bursts of high intensity exercise. However, because total energy expenditure increases with a faster rate of work, the amount of fat metabolised does increase.

Experiment 5: Carbohydrate and fat utilisation in exercise in the fed and fasting states

A 70 kg male student walked on a treadmill at 3.5 kph for 30 minutes in the early morning (after an overnight fast) and again 2 hours after eating breakfast.

From the figures for oxygen consumption and carbon dioxide production in the table below, calculate:

• his RQ (ratio of carbon dioxide produced / oxygen consumed) before and after breakfast
• the percentage of energy from carbohydrate and fat before and after breakfast (assuming he is metabolising only fat and carbohydrate)

In fasting the main fuel for muscle is fatty acids (sparing glucose for use by brain and red blood cells) – in the fed state there is plenty of glucose and it becomes main fuel for muscle. Note that glucose uptake into muscle is dependent on insulin, which is low in fasting state, hence there is little glucose uptake into muscle in the fasting state.

Key points from this exercise:

• In exercise, creatine phosphate acts as a reservoir of "high energy" phosphate to maintain the intracellular concentration of ATP until metabolic activity increases. It also acts to shuttle "high energy" phosphate from ATP formed in mitochondria to the sites where ATP is required for muscle contraction.
• The selection of fuels for muscle work depends on:
• the intensity of the exercise
• the duration of the exercise
• whether in the fed or fasting state
• At rest, muscle is relatively poorly perfused and metabolises mainly its own glycogen reserves, largely anaerobically, producing lactate.
• In short duration, high intensity exercise, which uses glycolytic white muscle fibres, the main fuels are muscle glycogen and plasma glucose. As much as possible is metabolised aerobically, but the rate of uptake of oxygen is insufficient and there is much anaerobic glycolysis to form lactate.
• In moderate exercise the main fuel initially is glucose muscle glycogen. As the exercise continues, and muscle glycogen begins to be depleted, so there is an increasing uptake of plasma glucose and fatty acids. The oxidation of fatty acids increases as glucose and glycogen reserves are depleted.
• In strenuous exercise, the oxidation of fatty acids is insufficient to meet the need for ATP formation, and an increasing proportion of glucose is oxidised as the intensity of the exercise increases.
• In the fasting state the main fuel for muscle is fatty acids. In the fed state, when much glucose is available and insulin secretion is high, muscle take sup and uses mainly glucose.