• Even at rest there is some work being performed by muscles - to maintain circulation and breathing and generally maintain muscle tone.
• Sodium, potassium and calcium ions are transported across cell membranes and between intracellular compartments by active transport, which is energy requiring.
• There is continual breakdown of tissue proteins and replacement synthesis - both processes are energy requiring.
• Many enzyme catalysed reactions are endothermic and require an input of energy.

BMR is the energy expenditure by the body when completely at rest, but awake, at a comfortable temperature and about 4 hours after a meal.

Some people lower their metabolic rate and body temperature slightly when they are asleep. In other people there is an increase in metabolic rate, and an increase in heat output from the body, when they are asleep.

This is the effect of activation of uncoupling proteins in muscle and brown adipose tissue. Some people, who do not gain weight readily respond to leptin and other hormones secreted by adipose tissue to increase energy expenditure, and so reduce adipose tissue reserves, when they are asleep. Other people, whose body temperature falls when they are asleep, are biologically more efficient, conserving their energy reserves. They are more likely to gain weight with a small excess of food intake over energy expenditure.

This is to ensure that energy is not being expended in either thermogenesis to compensate for a low external temperature or sweating and vasodilatation to lose excess heat from the body.

This is to ensure that energy is not being expended on synthesis and secretion of digestive enzymes, active transport for the absorption of the products of digestion and synthesis of body reserves of metabolic fuel. This is known as diet-induced thermogenesis, the increase in metabolic rate after a meal - there is more on this later in this exercise.

The "gold standard" method is to measure heat output from the body in an insulated room that is maintained at a constant temperature by passing cold water through pipes and measuring the increase in temperature of the water. It is also possible to measure the energy expenditure in a limited number of activities (and for a limited time) in the same way.

More usually, BMR and energy expenditure in physical activity are measured by measuring oxygen consumption.

To first approximation there is an energy expenditure of 20 kJ for each litre of oxygen consumed.

This means that it is possible to measure energy expenditure in a wider range of activities, for a longer period, and under more or less normal conditions, rather than in the somewhat artificial conditions of a metabolic chamber.

By measuring the ratio of carbon dioxide formed : oxygen consumed (the respiratory quotient, RQ):

Thus, an RQ near to 1 indicates that mainly carbohydrate is being oxidised, and RQ near 0.7 indicates that mainly fat is being oxidised.

Urea is the end-product of metabolism of the amino groups of amino acids. The urinary excretion of urea therefore reflects the amount of amino acids arising from dietary protein or tissue proteins being metabolised.

By using dual isotopically labelled water (i.e. water containing both deuterium (2H) and 18O, both of which are stable isotopes. The loss of the two labels from any body fluid (most conveniently urine) is followed for a period of several days or weeks after drinking a sample of the labelled water.

The deuterium label is lost from the body only in water.

By contrast, the oxygen label is lost from the body in both water and carbon dioxide, because of the rapid equilibrium between carbon dioxide and bicarbonate - all three atoms of oxygen in bicarbonate are equivalent and each is as likely as the others to end up in carbon dioxide or water:

From the difference in rate constants for the loss of the deuterium and hydrogen labels from body water it is possible to calculate the total amount of carbon dioxide produced over the period. Knowing the approximate mix of metabolic fuels consumes, it is then possible to calculate total energy expenditure in a non-invasive way that does not interfere with the subject's normal activities.

PAR is the energy expended in a given physical activity expressed as a multiple of the BMR. Very light activities have a PAR of between 1.0 - 1.4 times BMR; very heavy physical activity may have a PAR as high as 6 - 8 times BMR.

Physical activity ratios in different types of activity are as follows (you do not need to know these figures):

• PAR 1.0 - 1.4
  • Lying, standing or sitting at rest, e.g. watching TV, reading, writing, eating, playing cards and board games
• PAR 1.5 - 1.8
  • sitting: sewing, knitting, playing piano, driving
  • standing: preparing vegetables, washing dishes, ironing, general office and laboratory work
• PAR 1.9 - 2.4
  • standing: mixed household chores, cooking, playing snooker or bowls
• PAR 2.5 - 3.3
  • standing: dressing, undressing, showering, making beds, vacuum cleaning
  • walking: 3 - 4 km/h, playing cricket
  • occupational: tailoring, shoemaking, electrical and machine tool industry, painting and decorating
• PAR 3.4 - 4.4
  • standing: mopping floors, gardening, cleaning windows, table tennis, sailing
  • walking: 4 - 6 km/h, playing golf
  • occupational: motor vehicle repairs, carpentry and joinery, chemical industry, bricklaying
• PAR 4.5 - 5.9
  • standing: polishing furniture, chopping wood, heavy gardening, volley ball
  • walking: 6 - 7 km/h
  • exercise: dancing, moderate swimming, gentle cycling, slow jogging
  • occupational: labouring, hoeing, road construction, digging and shovelling, felling trees
• PAR 6.0 - 7.9
  • walking: uphill with load or cross-country, climbing stairs
  • exercise: jogging, cycling, energetic swimming, skiing, tennis, football
    

  Classification of types of occupational work by PAR (average PAR through 8h working day, excluding leisure activities)

• Light work (PAR = 1.7)
  • professional, clerical and technical workers, administrative and managerial staff, sales representatives, housewives
• Moderate work (PAR = 2.2 for women, 2.7 for men)
  • sales staff, domestic service, students, transport workers, joiners, roofing workers
• Moderately heavy work (PAR = 2.3 for women, 3.0 for men)
  • machine operators, labourers, agricultural workers, bricklaying, masonry
• Heavy work (PAR = 2.8 for women, 3.8 for men)
  • labourers, agricultural workers, bricklaying, masonry where there is little or no mechanisation

PAL is the sum of the PAR for each activity during the day x fraction of 24 hours spent in that activity, expressed as multiple of BMR

DIT is the increase in metabolic rate after a meal. It is the energy expenditure for synthesis and secretion of digestive enzymes, active transport for the absorption of the products of digestion and, most importantly, the synthesis of body reserves of metabolic fuel. Altogether it may represent 10 - 15% of the energy yield of a meal.

You could do this by estimating their BMR, which depends on gender, age and body weight from standard tables, such as that shown below (which is for reference only - you do not need to know the figures, just be aware that BMR:

• is higher in men than in women of the same body weight
• increases with increasing body weight
• decreases with age even if body weight remains constant

Then you need to estimate their physical activity. The easiest way to do this is to keep a diary of activities (see the list of PAR for different activities above) and the time spent in each activity, so that you can calculate their PAL, and make an approximation of their DIT.

TEE = PAL x BMR + DIT

There is a gender difference in body composition - women have higher reserves of adipose tissue than do men of the same weight. This is because women have evolved to have adequate reserves of adipose tissue to permit then to carry a pregnancy and lactation during a time when food was scarce.

Adipose tissue is metabolically active, but considerably less so per gram of tissue than muscle or other lean tissues. This is because ~80% of the mass of adipose tissue is triacylglycerol rather than metabolically active cytosol.

Again this is due to changes in body composition. There is a gradual loss of active muscle with increasing age, and the development of larger reserves of triacylglycerol between muscle fibres.

The main metabolic fuels are glucose, fatty acids (either as free (non-esterified) fatty acids in the circulation or triacylglycerol in plasma lipoproteins) and ketone bodies.

Ideally the diet should provide 55% of energy from carbohydrate, 30% from fat and 15% from protein. (Average western diets provide more fat than this, about 40%, and this is associated with obesity and increased risk of cardiovascular disease and cancer)

The figure of 15% of energy from protein is about 2 x higher than the requirement for protein (see later exercises), but it reflects the average intake of protein in developed countries. Since there is no hazard in consuming this amount of protein, and no advantage in reducing the intake, there is not considered to be any need to change average protein intakes. The key public health target is to reduce fat intake (and especially saturated fat, see later exercises), and replace it with carbohydrate (and increase the proportion of carbohydrate coming from starches, while reducing that from sugars).

The energy yields of metabolic fuels are:

• carbohydrate 16 kJ /g
• protein 17 kJ /g
• fat 37 kJ /g
• alcohol 29 kJ /g

From these figures is is easy to calculate:

• energy from carbohydrate = grams carbohydrate x 16 kJ
• energy from protein = grams protein x 17 kJ
• energy from fat = grams fat x 37 kJ
• energy from alcohol = grams alcohol x 29 kJ

Total energy intake = energy from carbohydrate + energy from protein + energy from fat + energy from alcohol

• percent energy from carbohydrate = (energy from carbohydrate / total energy) x 100
• percent energy from protein = (energy from protein / total energy) x 100
• percent energy from fat = (energy from fat / total energy) x 100
• percent energy from alcohol = (energy from alcohol / total energy) x 100

We can define two normal metabolic states:

• The fed state, up to about 4 hours after a meal, when the products of digestion are being absorbed;
• The fasting state, when all the products of digestion have been absorbed.

In the fed state glucose will be the main fuel for all tissues.

Glucose in excess of immediate requirements for tissues will be used in liver and muscle to synthesise the storage carbohydrate, glycogen, which is a polymer of glucose linked 1-4, with branches each 10 or so glucose units formed by 1-6 glycoside bonds.

Glucose in excess of immediate requirements for tissues will be also used in liver and muscle to synthesise fatty acids and triacylglycerol. Triacylglycerol synthesised in the liver is exported in very low density lipoprotein and is available for uptake into other tissues for storage or use as a metabolic fuel, and into adipose tissue for storage.

In the fed state the fatty acids arising from the digestion of dietary fats are re-esterified to triacylglycerol in the intestinal mucosa and enter the circulation (via the lymphatic system) in chylomicrons. Adipose tissue and muscle take up fatty acids from chylomicrons by the action of extra-cellular lipoprotein lipase, and esterify them for storage. The liver takes up the chylomicron remnants and exports the remaining triacylglycerol, together with triacylglycerol synthesised from glucose in very low density lipoprotein.

In the fasting state the plasma concentration of glucose has to be maintained above about 3.5 mmol /L because the brain is very largely , and red blood cells are entirely, reliant on glucose as a metabolic fuel.

Initially liver glycogen is used to provide a glucose. Muscle glycogen is mainly required as a fuel for muscle itself in vigorous exercise, but can provide a source of blood glucose indirectly (there is more on this in a later exercise). Glycogen is broken down to glucose 1-phosphate, which is then isomerised to glucose 6-phosphate. Muscle cannot liberate glucose from glycogen because it lacks the enzyme glucose 6-phosphatase.

As glycogen reserves begin to be depleted, glucose is synthesised from amino acids liberated by tissue protein catabolism. This is the process of gluconeogenesis. There is continual turnover of tissue proteins, and in the fasting state most of the amino acids released by protein catabolism are used for gluconeogenesis. This means that in the fasting state there is a net catabolism of tissue protein, which is replaced in the fed state, when there is an adequate supply of both glucose and new amino acids arising from the digestion of dietary protein.

The triacylglycerol reserves in adipose tissue are hydrolysed by an intracellular lipase (hormone sensitive lipase), liberating free (non-esterified) fatty acids and glycerol. The glycerol is taken up by the liver and is a substrate for gluconeogenesis. The fatty acids are taken up by tissues and used as a metabolic fuel.

Note that, for reasons that will become apparent in later exercises, fatty acids can never be a substrate for gluconeogenesis.

Soap consists of the sodium salts of fatty acids; it owes its detergent action to the fact that the long hydrophobic tail of the fatty acid can dissolve in lipids, while the carboxyl group interacts with water, permitting the formation of small droplets of lipid emulsified in water. In the same way, fatty acids will dissolve in cell membranes and lyse them. Binding fatty acids to serum albumin prevents this happening.

In addition, the calcium salts of fatty acids are insoluble, and fatty acids in free solution would react with the free ionised calcium in the bloodstream, which must be maintained within a very narrow range to maintain normal nerve and muscle excitability. If plasma free calcium falls too low there is a danger of uncontrolled muscle contraction (tetany). If it rises too high there is a danger of calcification of soft tissues. Possibly more importantly, the insoluble calcium salts of fatty acids would block small blood vessels. Again, binding fatty acids to serum albumin prevents them reacting with calcium.

Although the fatty acids are bound to serum albumin, it is equilibrium binding - i.e. non-covalent. There is an equilibrium between albumin-bound and free fatty acids, predominantly towards bound, but there is always a very small amount in free solution. This is available to diffuse into tissues, where it is immediately esterified with coenzyme A to form fatty acyl CoA. As long as there is free CoA in the cell, this will ensure a inwards concentration gradient of fatty acid. As it is removed from free solution in the bloodstream by entering cells and being sequestered by CoA, so the equilibrium between bound and free fatty acid in the bloodstream will be restored, liberating more fatty acid that is available for tissue uptake.

Acetoacetate and hydroxybutyrate are synthesised in the liver, from acetyl CoA arising from the oxidation of fatty acids that have come from the hydrolysis of adipose tissue triacylglycerol. Acetone arises by non-enzymic breakdown of acetoacetate. It is poorly metabolised, and formation of acetone represents a loss of potentially valuable triacylglycerol reserves.

The importance is two-fold:

• Hydroxybutyrate is chemically stable, whereas acetoacetate in not, and undergoes non-enzymic decarboxylation to acetone, which is poorly metabolised. This means that formation of hydroxybutyrate prevents excessive loss of metabolic fuel.
• In extrahepatic tissues, hydroxybutyrate is oxidised back to acetoacetate, which is then cleaved to yield 2 mol of acetyl CoA for oxidation in the mitochondria. The oxidation of hydroxybutyrate to acetoacetate yields NADH, which is re-oxidised in the mitochondrial electron transport chain, yielding an additional ~2.5 ATP. Thus the liver effectively exports additional reducing power, which yields additional ATP, when it reduces acetoacetate to hydroxybutyrate.

Muscle has a limited capacity for fatty acid oxidation, and cannot oxidise enough fatty acids to meet all of its energy needs. By contrast, the liver can oxidise more fatty acids than it needs to meet its own energy requirements. The liver metabolises fatty acids to acetyl CoA in excess of its needs for acetyl CoA, then synthesises acetoacetate and hydroxybutyrate for export to other tissues as an additional metabolic fuel.

In relatively advanced starvation, when ketone body concentrations have risen relatively high, they become a significant fuel for the brain as well, so reducing the need for gluconeogenesis from amino acids.

We saw in the exercise starving to slim that blood glucose falls initially, then is maintained at a reasonably constant level, initially from breakdown of glycogen reserves, then by gluconeogenesis from amino acids. Free fatty acids increase form the fed to fasting state, but then do not rise further. What increases as fasting progresses into starvation is the plasma concentration of ketone bodies.

When the concentration of ketone bodies is high enough for them to be a significant fuel for the brain, there is less demand for glucose, and the blood glucose concentration falls somewhat. There is still a need to provide glucose for red blood cells, since they lack mitochondria, and so cannot metabolise ketone bodies.

Insulin is the main hormone of the fed state. It is secreted by the beta-cells of the pancreatic islets in response to an increase in the blood concentration of glucose. In response to a decrease in the blood concentration of glucose, insulin secretion falls, and there is increased secretion of glucagon by the alpha-cells of the pancreatic islets.

The key roles of insulin are in the stimulation of synthesis of reserves of glycogen, fatty acid and triacylglycerol in the fed state.

The key roles of glucagon are in the mobilisation of metabolic fuels from these reserves.

The actions of adrenaline resemble those of glucagon - in preparation for rapid action there is a need to increase the plasma concentration of metabolic fuels by mobilising reserves of glycogen from the liver and triacylglycerol from adipose tissue.

In the fasting state the glucose transporters in muscle and adipose tissue are in intracellular vesicles. In response to insulin these vesicles migrate to the cell surface and fuse with the cell membrane, so inserting glucose transporters into the cell membrane. Under these conditions muscle and adipose tissue can take up glucose - for metabolism as the main fuel and synthesis of glycogen in muscle, and for synthesis of fatty acids and triacylglycerol in adipose tissue. As insulin secretion falls, and glucagon secretion increases in response to lower blood glucose concentration, so the transporters are internalised again, so that muscle and adipose tissue can no longer take up glucose. This means that in the fasting state muscle and liver do not take up glucose, so sparing it for use by the brain and red blood cells.

Muscle and adipose tissue simply require glucose transporters that will permit uptake of glucose when the blood concentration is high. By contrast, the liver needs to take up glucose when the blood concentration is high, but needs to export glucose (from the breakdown of glycogen and from gluconeogenesis) when the blood concentration is low. This means that the glucose transporters in the liver need to be bidirectional, and always need to be exposed in the cell membrane.

When the blood glucose concentration is relatively high (and it can reach 20 mmol /L in the hepatic portal vein after a meal), glucose is trapped in the liver by phosphorylation to glucose 6-phosphate. Although glucose can cross the liver cell membrane freely, glucose 6-phosphate cannot cross the membrane at all, but remains in the cell. This means that if glucose is phosphorylated immediately it enters the liver cells, there is a net inwards flux of glucose.

There are two isoenzymes in the liver that catalyse the phosphorylation of glucose to glucose 6-phosphate. One, hexokinase, has a low Km, and is saturated, and therefore acting at its maximum rate, at a very low concentration of glucose. The other, glucokinase, has a high Km (about 20 mmol /L) and so its activity increases as the concentration of glucose entering the liver cell increases.

In the fasting state there is continuous production of glucose in the liver, from breakdown of glycogen reserves and as a result of gluconeogenesis, so that the intracellular concentration is higher than that in the bloodstream.

In the liver, hexokinase always acts at its maximum rate, and therefore always brings in a constant amount of glucose. This is presumably the amount of glucose that is required by the liver for its own metabolism (although it can always meet its own glucose requirements form its glycogen reserves and gluconeogenesis).

Glucokinase is only significantly active when the concentration of glucose in the blood reaching the liver is high. It acts to trap glucose in the liver, for the synthesis of glycogen and fatty acids. Although the concentration of glucose coming from the small intestine to the liver in the hepatic portal vein may reach 20 mmol /L, the concentration of glucose leaving the liver in the vena cava is rarely above 8 - 10 mmol /L.

An overview of metabolic processes in the fed state

An overview of metabolic processes in the fasting state

Key points from this exercise:

• Even at rest there is some work being performed by muscles - to maintain circulation and breathing and generally maintain muscle tone.
• Sodium, potassium and calcium ions are transported across cell membranes and between intracellular compartments by active transport, which is energy requiring.
• There is continual breakdown of tissue proteins and replacement synthesis - both processes are energy requiring.
• Many enzyme catalysed reactions are endothermic and require an input of energy.
• BMR is the energy expenditure by the body when completely at rest, but awake, at a comfortable temperature and about 4 hours after a meal.
• The "gold standard" method is to measure heat output from the body in an insulated room that is maintained at a constant temperature by passing cold water through pipes and measuring the increase in temperature of the water. It is also possible to measure the energy expenditure in a limited number of activities (and for a limited time) in the same way.
• More usually, BMR and energy expenditure in physical activity are measured by measuring oxygen consumption. To first approximation there is an energy expenditure of 20 kJ for each litre of oxygen consumed.
• The ratio of carbon dioxide formed : oxygen consumed (the Respiratory Quotient, RQ) differs for oxidation of fat, carbohydrate and protein. An RQ near to 1 indicates that mainly carbohydrate is being oxidised, and RQ near 0.7 indicates that mainly fat is being oxidised. Measurement of urinary excretion of urea permits estimation of the amount of amino acids being oxidised.
• The deuterium label from dual isotopically labelled water is lost from the body only in water, while the label in 18O is lost on both water and carbon dioxide. Measuring the rate of loss of both isotopes from body fluids permits estimation of the total amount of carbon dioxide produced over a period of 14 days or more, and so permits estimation of total energy expenditure over this period.
• Physical Activity Ratio (PAR) is the energy expended in a given physical activity expressed as a multiple of the BMR. Very light activities have a PAR of between 1.0 - 1.4 times BMR; very heavy physical activity may have a PAR as high as 6 - 8 times BMR.
• Physical Activity Level (PAL) is the sum of the PAR for each activity during the day x fraction of 24 hours spent in that activity, expressed as multiple of BMR .
• Diet Induced Thermogenesis (DIT) is the increase in metabolic rate after a meal. It is the energy expenditure for synthesis and secretion of digestive enzymes, active transport for the absorption of the products of digestion and, most importantly, the synthesis of body reserves of metabolic fuel. Altogether it may represent 10 - 15% of the energy yield of a meal.
• BMR is higher in men than in women of the same body weight and age because women have higher reserves of adipose tissue than do men of the same weight.
• BMR falls with increasing age, even if body weight remains unchanged because of changes in body composition. There is a gradual loss of active muscle with increasing age, and the development of larger reserves of triacylglycerol between muscle fibres.
• The main metabolic fuels are glucose, fatty acids (either as free (non-esterified) fatty acids in the circulation or triacylglycerol in plasma lipoproteins) and ketone bodies.
• Ideally the diet should provide 55% of energy from carbohydrate, 30% from fat and 15% from protein. (Average western diets provide more fat than this, about 40%, and this is associated with obesity and increased risk of cardiovascular disease and cancer) .
• In the fed state glucose will be the main fuel for all tissues. Glucose in excess of immediate requirements for tissues will be used in liver and muscle to synthesise the storage carbohydrate, glycogen. It will be also used in liver and muscle to synthesise fatty acids and triacylglycerol.
• In the fasting state liver glycogen is used to provide a source of glucose initially. Muscle glycogen is mainly required as a fuel for muscle itself in vigorous exercise, but can provide a source of blood glucose indirectly.
• As glycogen reserves begin to be depleted, glucose is synthesised from amino acids liberated by tissue protein catabolism (the process of gluconeogenesis).
• The triacylglycerol reserves in adipose tissue are hydrolysed by an intracellular lipase (hormone sensitive lipase), liberating free (non-esterified) fatty acids and glycerol. The glycerol is taken up by the liver and is a substrate for gluconeogenesis. The fatty acids are taken up by tissues and used as a metabolic fuel. Fatty acids can never be a substrate for gluconeogenesis.
• Fatty acids will dissolve in cell membranes and lyse them; binding them to serum albumin prevents this happening
• Fatty acids in free solution would react with the free ionised calcium in the bloodstream; the calcium salts of fatty acids are insoluble. Again binding fatty acids to serum albumin prevents them reacting with calcium.
• Muscle has a limited capacity for fatty acid oxidation, and cannot oxidise enough fatty acids to meet all of its energy needs. By contrast, the liver can oxidise more fatty acids than it needs to meet its own energy requirements. The liver metabolises fatty acids to acetyl CoA in excess of its needs for acetyl CoA, then synthesises acetoacetate and hydroxybutyrate for export to other tissues as an additional metabolic fuel.
• The ketone bodies acetoacetate and hydroxybutyrate are synthesised in the liver. Acetone arises by non-enzymic breakdown of acetoacetate. It is poorly metabolised, and formation of acetone represents a loss of potentially valuable triacylglycerol reserves.
• In extrahepatic tissues, hydroxybutyrate is oxidised back to acetoacetate, which is then cleaved to yield 2 mol of acetyl CoA for oxidation in the mitochondria. The oxidation of hydroxybutyrate to acetoacetate yields NADH, which is re-oxidised in the mitochondrial electron transport chain, yielding an additional ~2.5 ATP. Thus the liver effectively exports additional reducing power, which yields additional ATP, when it reduces acetoacetate to hydroxybutyrate.
• In relatively prolonged starvation, when the concentration of ketone bodies is high enough for them to be a significant fuel for the brain, there is less demand for glucose, and the blood glucose concentration falls somewhat. There is still a need to provide glucose for red blood cells, since they lack mitochondria, and so cannot metabolise ketone bodies.
• Insulin is the main hormone of the fed state. It is secreted by the beta-cells of the pancreatic islets in response to an increase in the blood concentration of glucose. In response to a decrease in the blood concentration of glucose, insulin secretion falls, and there is increased secretion of glucagon by the alpha-cells of the pancreatic islets.
• The key roles of insulin are in the stimulation of synthesis of reserves of glycogen, fatty acid and triacylglycerol in the fed state.
• The key roles of glucagon are in the mobilisation of metabolic fuels from these reserves.
• In the fasting state the glucose transporters in muscle and adipose tissue are in intracellular vesicles. In response to insulin these vesicles migrate to the cell surface and fuse with the cell membrane, so inserting glucose transporters into the cell membrane. Under these conditions muscle and adipose tissue can take up glucose - for metabolism as the main fuel and synthesis of glycogen in muscle, and for synthesis of fatty acids and triacylglycerol in adipose tissue. As insulin secretion falls, and glucagon secretion increases in response to lower blood glucose concentration, so the transporters are internalised again, so that muscle and adipose tissue can no longer take up glucose. This means that in the fasting state muscle and liver do not take up glucose, so sparing it for use by the brain and red blood cells.
• The liver can take up or release glucose, depending on the body's needs.
• In the fed state the liver takes up glucose by trapping it intracellularly as glucose 6-phosphate. There are two isoenzymes in the liver that catalyse the phosphorylation of glucose to glucose 6-phosphate. One, hexokinase, has a low Km, and is saturated, and therefore acting at its maximum rate, at a very low concentration of glucose. The other, glucokinase, has a high Km (about 20 mmol /L) and so its activity increases as the concentration of glucose entering the liver cell increases.
• The main contributor to diet-induced thermogenesis is the high ATP cost of synthesising glycogen, fatty acid and triacylglycerol, and protein.