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8 - Summary of Macronutrient Metabolism

Terms in this set (17)

Carbohydrates, lipids and proteins are all capable of providing the body with the energy that it needs on a short-term basis. This is of course assuming that sufficient quantities of these macronutrients are being eaten. When consumed in excess, all of these macronutrients are also capable of being stored in the body as fat. Furthermore, the body has the ability to produce one macronutrient from another if needed. For example, amino acids can be synthesised from carbohydrates or fats. Conversely, most amino acids can be used to synthesise carbohydrates or fat.
There are certain limitations to these processes. The glycerol component of fat can be converted to carbohydrate, however the fatty acid component cannot. This is because the reaction that uses pyruvate dehydrogenase is not reversible. Acetyl CoA (produced from the breakdown of fatty acids with an even number of carbons) is therefore unable to be converted into pyruvate (for the new synthesis of glucose). Glucose is however, the precursor for the synthesis of both the glycerol and fatty acid components of triglycerides.
This close relationship between the metabolism of carbohydrates, lipids and proteins is vital. The interconversion of the macronutrients is geared towards allowing the body to be able to maintain its supply of energy even when a particular macronutrient is insufficiently supplied.
The citric acid cycle is very important as it is central to macronutrient metabolism. It breaks down carbohydrates, lipids and proteins, as well as producing many of the precursors required for biosynthesis. It supplies the intermediate products that provide the links between lipids, carbohydrate and protein metabolism.
Most people tend to have a number of meals per day which are followed by periods where no food is consumed (although some people do like to 'graze' or nibble!). During a meal, the caloric intake (the intake of energy from food) is much greater than the body's immediate energy needs. This short period of excess energy intake allows people to go without food until the next meal.
The balance of glucose levels in the body must be maintained at a constant level both during meals and in the gaps between meals (the fasted state). It is important that tissues are adequately supplied with their preferred source of energy (glucose) throughout the course of the day. The mechanisms that the body uses to maintain a constant supply of blood glucose vary depending on the length of time in a fasted state.
When energy intake (the energy provided by food and beverages) exceeds energy expenditure, the excess energy is stored as glycogen or fat. Energy expenditure includes the energy required to breakdown, absorb, metabolise and store macronutrients, as well as the energy required for body functions such as breathing, the beating of the heart, temperature regulation and physical activity. Glycogen and fat stores can be used to provide the body with energy when required.
• Fed State - The body is considered to be in a fed state up to 3 hours after a meal has been eaten (obviously this depends on what was eaten and how much was eaten).
• Early Fasting State (post-absorptive) - From around 3 hours after a meal until 12 to 18 hours following a meal is considered to be an early fasting state (or a post-absorptive state).
• Fasting State - This lasts from around 18 hours after a meal, up to 2 days (without any food being consumed). The mechanisms used to maintain blood glucose levels change when a fasted state goes for longer than around 18 hours.
• Starvation or Long-Term Fast - The body adapts to the state of fasting. This adaptation can last as long as several weeks.
Red blood cells and the central nervous system use available glucose in the bloodstream as an immediate energy source. Glucose in the central nervous system is catabolised by glycolysis and then the citric acid cycle. Red blood cells do not have mitochondria, so they anaerobically convert glucose into lactate (via glycolysis), to create the small amount of energy that the cell requires.
Glucose that is not immediately needed by the body can be stored as glycogen. The liver is a major site for glycogen synthesis and storage, but it is also stored in skeletal muscle, and to a lesser extent, adipose tissue. Glycogen ensures that the body has a reserve of instant energy when it is required. Insulin enhances the activity of glycogen synthase, the enzyme that incorporates glucose into glycogen as UDP-glucose. The increased activity of glycogen synthase in the liver and muscles, is important for maximising the storage of glucose as glycogen in the fed state.
Once carbohydrate intake exceeds the body's ability to break it down through glycolysis or store it as glycogen, cells can metabolise it in a number of ways (e.g., the pentose phosphate pathway can use glucose to produce nucleotides). The conversion of excess glucose into fatty acids appears to only occur if energy intake exceeds energy expenditure. Insulin increases the activity of fatty acid and triglyceride synthesis enzymes (e.g., acetyl CoA carboxylase in the liver, lipoprotein lipase in adipose tissue and fatty acid synthetase). Fatty acids can then be stored in adipose tissue ready to provide energy during fasting states.
Most dietary fat is transported by chylomicrons (a lipoprotein transporter). Once in the intestinal mucosal cells, free fatty acids and monoglycerides (broken down in the digestive process) are re-formed into triglycerides and packaged into chylomicrons for transport. Chylomicrons pass into the lymphatic system, are transported to the thoracic duct, and are then emptied into the bloodstream. The chylomicrons then travel through the blood to adipose tissue. The enzyme lipoprotein lipase is present on the membrane of capillary cells near the adipocytes (fat cells). It binds the chylomicrons and cleaves the triglycerides into free fatty acids and monoglycerides. The free fatty acids and monoglycerides enter the adipocytes and are reformed into triglycerides for safe storage in adipose tissue. Insulin increases lipoprotein lipase activity in adipose tissue after feeding (lipoprotein lipase activity is low during fasted states).
The liver receives fat from chylomicron remnants, circulating fatty acids, lipoproteins and its own endogenous synthesis. In the fed state, the liver forms VLDLs with the fats and transports them to adipocytes for storage.
Under most circumstances, fatty acids are the major source of energy for the liver. They are oxidised through the citric acid cycle to product ATP. When there is an inadequate carbohydrate intake (even if caloric intake is adequate) or when glucose cannot be effectively used (e.g., diabetes mellitus), the breakdown of fatty acids (b-oxidation) is accelerated. Not all of the acetyl CoA formed is able to be oxidised through the citric acid cycle. The overflow of acetyl CoA is converted into keton bodies (acetoacetate and b-hydroxybutyrate). Ketone bodies are transported from the liver to peripheral tissues where they are converted back to acetyl CoA and oxidised through the citric acid cycle to generate ATP.
Polypeptides are broken down into amino acids and small peptides and are absorbed along the entire length of the small intestine. The majority of amino acids are thought to be transported across the brush border by sodium-dependent transporters. The same transporters are thought to carry the amino acids from the intestinal cells into the circulation, where they are taken to the liver for metabolism.
Many amino acids remain in the intestinal cells and are used by them for energy The intestinal cells also use amino acids to produce other amino acids, structural proteins for new intestinal cells, nucleotides, apoproteins necessary for lipoprotein formation, new digestive enzymes, hormones and nitrogen-containing compounds. The intestines may actually use up to 90% of glutamate absorbed from dietary protein.
The liver takes up most of the amino acids after the ingestion of a meal (around 50 to 65%). While amino acids are primarily used to synthesise new proteins in the body, excess amino acids can be catabolised to produce energy. The liver is thought to be able to monitor the absorbed amino acids and to make adjustments to their metabolism (breakdown or synthesis) according to the body's needs. Immediately after a meal is eaten, it is thought that around 20% of amino acids are used to synthesise proteins and nitrogen-containing compounds (e.g., neurotransmitters, carnitine, creatine, choline, nucleotides). Amino acids that are catabolised in the liver are mostly transaminated and then degraded to acetyl CoA or other citric acid cycle intermediates. These substances can then be oxidised by generate ATP, or converted to glucose or fat.
All amino acids can be used to produce energy. The carbon skeleton of glucogenic amino acids can be used to synthesise glucose when there is an inadequate calorie intake or insufficient carbohydrate intake. Glucose is formed via gluconeogenesis, and this new glucose can be transported to muscle for the muscle tissue to use. Ketogenic amino acids (which generate acetyl CoA or acetoacetate) can be catabolised to form ketone bodies when carbohydrate intake is insufficient. Fatty acids can be synthesised from the carbon skeletons of amino acids. The newly synthesised fatty acids can be used by the muscles for energy, or they can be transported to adipose tissue and stored. Fatty acid synthesis from amino acids occurs when there is an excess energy and protein intake, combined with an adequate carbohydrate intake.
At the state of the early fasting state (around 3 hours after a meal) the body can no longer derive its energy directly from ingested glucose or other macronutrients. It needs to start relying on other sources of fuel. During the early fasting state the major source of glucose for the bloodstream is from glycogenolysis (the breakdown of glycogen) in the liver (glycogenolysis occurs in muscles but the glucose produced is only able to be used as fuel by muscle cells). The glucose resides in glycogen are systematically cleaved from the ends of branches in accordance with the body's energy demands.
Glycogenolysis is regulated by the pancreatic hormone glucagon (and also epinephrine). Glucagon is secreted by pancreatic alpha cells and is released in response to lowered blood glucose levels. It binds to receptors on liver cells and stimulates the increased release of glucose into the blood. Glucagon (acting through cAMP) activates the enzyme protein kinase, which is responsible for the phosphorylation of many target enzymes. Protein kinase phosphorylates fructose bisphosphatase 2 (activating it) and phosphofructokinase 2 (inactivating it). This results in reduced concentration of fructose 2,6 bisphosphate; increasing gluconeogenesis and decreasing glycolysis. When glycogenolysis is occurring, the synthesis of glycogen and triglycerides in the liver is diminished. The new synthesis of glucose (gluconeogenesis) in the liver begins to help in maintaining blood glucose levels. Pyruvate, lactate, oxaloacetate, malate and glucogenic amino acids are all compounds that glucose can be synthesised from.
The brain and other central nervous system tissues consume a lot of glucose for energy. They also do not generate any gluconeogenic precursors. This means that glucose utilisation outstrips the liver's ability to produce glucose, and glycogen stores are rapidly diminished. During an overnight fast, nearly all liver glycogen and most muscle glycogen is used up.
If fasting becomes long-term or starvation occurs, the body shifts its metabolism to try and spare body protein. Protein is vital for the production of life-sustaining compounds such as antibodies, enzymes and haemoglobin. The body therefore shifts from predominantly relying on gluconeogenesis to lipolysis (the breakdown of fats) to provide energy. As fasting becomes prolonged, liver gluconeogenesis decreases from producing around 90% of the glucose in the body, to less than 50%. The kidneys start to supply the remainder of the glucose in the body through gluconeogenesis.
The amount of fatty acids in the bloodstream increases and fatty acids are used as the primary fuel for the heart, liver and muscles. Low insulin levels and raised glucagon, epinephrine, growth hormone and cortisol levels stimulate the release of fatty acids. The brain is unable to use the fatty acids (as they cannot cross the blood brain barrier), but it can use glycerol as a gluconeogenic precursor. The brain and muscles also continue to use ketone bodies for energy. Oxaloacetate becomes depleted as more and more citric acid cycle intermediates are used up for gluconeogenesis. The increased breakdown of fats and the depleted pool of oxaloacetate results in an accumulation of acetyl CoA. Under normal conditions, the liver would convert acetyl CoA into ketone bodies. They would be transported in the blood from the liver to peripheral tissues, where they would be converted back to acetyl CoA and used for energy (in the citric acid cycle). During starvation (and untreated diabetes mellitus) ketone bodies can accumulate in the blood and reach high concentrations. This results in ketosis, which is potentially dangerous due to the disturbance it causes to the body's acid-base balance.
The amount of time a person can survive using these mechanisms depends on their quantity of fat stores. A person with 'normal' weight and body fat stores is able to generate enough energy to sustain their body for around 3 months. While a very obese adult has enough energy stored to supply the body for around 12 months, physiological damage or death will occur from the damage caused by ketosis. Once fat stores have been depleted, the body once again turns to protein to supply the necessary fuel for ATP production. This causes a loss of muscle and liver function, which ultimately leads to death.