Metabolism
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Selection of fuels for muscle contraction
Even at rest, skeletal muscle accounts for more than one-fifth of total energy expenditure; obviously this increases greatly with exercise.
Muscle can use a variety of fuels, depending on the intensity of work being
performed, the duration of the exercise and also whether the individual is in
the fed or fasting state:
plasma glucose
muscle glycogen
triacylglycerol from plasma lipoproteins
triacylglycerol from adipose tissue reserves within the muscle
plasma non-esterified fatty acids
plasma ketone bodies
Skeletal muscle contains two types of fibres:
Experiment 1: Is ATP used in muscle contraction?
Rats
were anaesthetised and the gastrocnemius muscle on one hind limb was exposed
and subjected to electrical stimulation for three minutes to cause contractions.
The animals were killed, and both hind limbs were immediately immersed in liquid
nitrogen. The gastrocnemius muscles from both limbs were dissected out, and
the concentrations of ATP, ADP, creatine phosphate and creatine were measured.
| µmol /g muscle | unstimulated (at rest) | after stimulation |
| ATP | 5 | 4.9 |
| ADP | 0.01 | 0.11 |
| creatine phosphate | 17 | 1.0 |
| creatine | 0.1 | 16.1 |
What conclusions can you draw from these results?
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 (from glycolysis in the cytosol and oxidative phosphorylation in 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.
Can you account for this gender difference in creatinine excretion?
Creatinine formation depends on total creatine content of the body, mainly in
muscle; higher creatinine excretion reflects high proportion of muscle in males.
Why is it usual to express urinary excretion of various metabolites per mol
of creatinine rather than per litre of urine?
Urine volume, and hence concentration of metabolites, is highly variable; creatinine excretion is reasonably constant from day to day.
Urinary excretion of creatine is normally < 400 µmol /day. Under what
conditions would you expect creatine excretion to be increased significantly?
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.
nmol /g muscle /min |
|||
at rest |
1 twitch / sec |
5 twitches /sec |
|
| glucose uptake | 64 |
215 |
783 |
| oxygen uptake | 576 |
2592 |
6912 |
| lactate output | 297 |
188 |
1112 |
| ratio lactate output : glucose uptake | 4.6 |
0.87 |
2.3 |
A muscle biopsy sample was taken from both the stimulated and unstimulated leg for measurement of glycogen (µmol glucose equivalent /g muscle).
| glycogen (µmol glucose equivalent /g muscle) | |
| resting | 314 |
| 1 twitch /sec | 307 |
| 5 twitches /sec | 213 |
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.
What conclusions can you draw from these results?
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.
What would you expect the maximum ratio of lactate output : glucose uptake to be under anaerobic conditions?
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.
What is the source of this lactate in excess of what can be derived from the glucose taken up by the muscle?
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 below 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.
What conclusions can you draw from these results?
The graph on the left above 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.
energy yield, kJ /g |
oxygen consumed, L /g |
carbon dioxide produced, L /g |
RQ |
kJ /L oxygen |
|
| carbohydrate | 16 |
0.829 |
0.829 |
1.0 |
~ 20 |
| protein | 17 |
0.966 |
0.782 |
0.809 |
~20 |
| fat | 37 |
20.16 |
1.427 |
0.707 |
~ 20 |
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
L oxygen |
kJ /30 min |
PAR |
L carbon dioxide |
RQ |
% energy from carbohydrate |
% energy from fat |
g fat metabolised |
|
| at rest | 9.1 |
1.0 |
6.6 |
|||||
| 1 kph | 14.4 |
10.4 |
||||||
| 3.5 kph | 26.6 |
19.5 |
||||||
| 5 kph | 33.0 |
26.0 |
||||||
| 6.5 kph | 47.2 |
38.7 |