Metabolic and Biochemical Alterations - Assignment Example

Principle characteristic metabolic and biochemical alterations that take place during sustained moderate high intensity exercise Although moderate exercise can benefit health, rigorous exercise regime can be sometimes hazardous to health. Regular exercise will reduce the risk of chronic diseases such as cancer, diabetes, cardiovascular diseases. However the amount of exercise required to achieve beneficial effects has not been clearly defined but to gain maximum health benefits, the frequency, intensity and the duration of exercise and pre-exercise fitness levels will be important determents. (5) Rigorous physical activity can trigger an acute myocardial infarction and increase the occurrence of premature ventricular depolarisations which has been associated with long-term increase in the risk of cardiovascular deaths (3) Carbohydrate and fat are the main fuels used during high intensity exercise. The major form of Carbohydrate is in the form of glycogen present in liver and skeleton muscle. There are 2 sources of fat oxidized during high intensity exercise- Nonesterified fatty acids (NEFA) released from adipose tissue and triacylglycerol deposits transported to the skeletal muscle through bloodstream. Adipose tissue traicylglycerols comprise 150-200 g/kg body mass in men and 250-300 g/kg body mass in women. There is an increase of 5-10% for fat and glucose oxidation during mild and moderate intensity exercise. (12) High intensity training requires greater capacity for the use of carbohydrate for energy production. All muscular activity is dependent on the availability of substrates for ATP production. Muscles can store circulating blood glucose or lipids. High intensity exercise require greater amount of ATP production in the body that is exploited from intracellular phosphagens or glycogen. However, there would be depletion of both the resource would result in fatigue. Adequate ATP levels must be maintained in order to avoid fatigue as ATP is required for generation of adequate sodium potassium in the body which is essential for maintaining normal sarcolemma. In addition to this, ATP also stabilizes the SR CA++ release channel. During the heavy contractile activity, there is decline in ATP content from 5 to 1.5 mM. Carbohydrate feeding through the rigorous exercise prevents fatigue by an hour but does not prevent fatigue or change the rate of muscle glycogen depletion. Carbohydrate is the main nutrient that fuels exercise of a moderate to high intensity because only carbohydrates can be easily mobilized in the body to meet the energy requirements (14). There are 2 main sources of energy during intensity exercise which is fat (triglyceride) and carbohydrate (glucose and glycogen) which is stored within the body. Glycogen is a very essential component during high intensity exercise because the fat can slowly convert into energy during these exercises. Hence the muscle glycogen and blood glucose should be high to match up with the energy level required to perform strenuous exercises. Fat is stored in the form of triglyceride which consists of free fatty acids. Triglyceride is also stored directly within muscle fibres which are called intramuscular triglyceride. It accounts to 2000-3000 Kcal of stored energy. (13) During strenuous exercise, intramuscular triglyceride is considered as supplementary to that supplied by muscle glycogen. During high intensity exercise, large amount of triglyceride are mobilized at a slow rate and in this process, the exercise stimulates an enzyme hormone sensitive lipase to dissolve the lipid into free fatty acids (FFA) and this process of breaking down triglyceride is called as lipolysis. The contribution of carbohydrate i.e. muscle glycogen and blood glycose, fat from plasma FFA and intramuscular triglyceride to total energy expenditure during high intensity exercise. The primary carbohydrate fuel switches from muscle glycogen to blood glucose after the first 2 hours of intense exercise. Ingested triglyceride (MCT) is directly absorbed into the blood and is rapidly broken down by fatty acids and glycerol. Exercise can elicit changes in the cellular and humoral immune systems and strenuous exercise can induce inflammatory reactions and immune disturbances. (11) Principle characteristic metabolic and biochemical alterations that take place during the “fed” state after a large meal containing high carbohydrate and fat content The food that we intake during a meal is digested by the body and this process is called ‘metabolism’. (10) In fed state the regulatory mechanism such as the availability of substrates; allosteric regulation of enzymes; covalent modification of enzymes; induction repression of enzyme synthesis ensure that adequate nutrients are captured as glycogen. (4) An allosteric effect usually involves rate determining reactions. For instance, glycolysis in the liver is stimulated following a meal by an increase in fructose. Many enzymes are regulated by the addition or removal of phosphate groups from specific serine. In the fed state, most the enzymes are regulated by these covalent modifications are in dephosphorylated form are active. Increased or decreased protein synthesis leads to changes in the total population of active sites. In the fed state elevated insulin levels result in increase in the synthesis of key enzymes such as acetyl coenzyme (CoA).Under these conditions, glucose is a major fuel for oxidation in tissues, after we consume and digest a large meal containing high protein fat and carbohydrate content, glucose and amino acids are transported from the intestine to the blood. Glucose uptake into the muscle and adipose tissue is controlled by insulin which is secreted by cells of pancreas because of increased concentration of glucose in the blood. The absorptive state is the 2 to 4 hour period after ingestion of the normal meal. During the interval, transient increases in plasma glucose, amino acids and triacylglycerols occur. (10) During absorptive period, the liver takes up carbohydrates, lipids, and amino acids. These nutrients are then metabolized stored and routed to other tissues. Thus, the liver smoothes out the availability of nutrients for the peripheral tissues. (1) The insulin sensitive tissues will only take up glucose from the blood stream to any significant extent in the presence of hormones. Insulin signals the fed state and it stimulates the storage of fuel and synthesis of proteins in several ways. For instance, insulin initiates protein which stimulates glycogen synthesis in both muscle and the liver. Insulin also accelerates glycolysis in the liver which in turn increases the synthesis of fatty acid. In adipose tissue, insulin stimulates glucose uptake, its conversion to fatty acids and inhibits intracellular lipolysis and the release of fatty acids. (1) The energy metabolism of the skeletal muscle is unique in being able to respond to substantial changes in the demand for ATP that accompanies muscle contraction. Glucose is phosphorylated to glucose 6-phosphate and metabolized to provide energy for the cells. Fatty acids are released from chylomicrons by the action of lipoprotein lipase. However, fatty acids are secondary importance as a fuel to muscle during well fed state in which glucose is the primary source of energy and fuel. A spurt in amino acid intake and protein synthesis occurs in absorptive state after ingestion meal containing carbohydrates and rich protein. The brain is vital to the proper functioning of the body and hence more priority will be given to its fuel needs. (1). In the well fed state, the brain uses glucose exclusively as fuel completely oxidizing 140g /day to carbon dioxide and water. The brain contains no significant stores of glycogen and is completely dependent on the availability of blood glucose. (4) There is net protein catabolism in the postabsorptive phase of the feeding cycle and net protein synthesis in the absorptive phase when the rate of synthesis increases by 20 to 25%.The increased rate of protein synthesis is a response to insulin action. Protein synthesis is an energy expensive process which accounts almost to 20% of the energy expenditure in the fed state where there is abundance of amino acids from the diet but only 9% under starved state. (2) Principle characteristic metabolic and biochemical alterations that take place during food starvation Fasting may result from inability to obtain food from the desire to lose weight rapidly or in any clinical situations. In the absence of food, plasma levels of glucose, amino acids and TAG fall, triggering a decline in insulin secretion and an increase in glucagon release. (9) This instigates an exchange of substrates between liver, adipose tissue, muscle and the brain that is guided by 2 priorities which are 1) The need to maintain adequate plasma levels of glucose to sustain adequate energy of the brain, red blood cells and glucose requiring tissues. 2) The need to mobilize fatty acids from adipose tissues and the synthesis and release of ketone bodies from the liver, to supply energy to all other issues. It is known that prolonged starvation and fasting leads to a reduction in resting metabolic rate( RMR) and induces immunodeficiency characterized by disproportionate loss of lymphoid tissue impaired cell mediated immunity and increased susceptibility to infectious diseases. This is both due to decrease in body mass and to a fall in the energy expenditure of the remaining body tissues. A typical well nourished man weighing 70 kg has fuel reserves totalling 161,000 kcal. The energy required for a day ranges from 1600 kcal to 6000kcal depending upon the extent of activity. Thus, stored fuel suffices to meet caloric needs of starvation for 1-3 months. However, the carbohydrate reserves are exhausted within a day. (8) Fasting induces profound changes in the body in order to decrease the energy expenditure and to conserve energy. Even under starvation period, the blood glucose level must be maintained above 2.2 mm. The first priority of metabolism in starvation is to provide adequate glucose to the brain and other tissues, red blood cells which are adequately dependent on this fuel. Most energy is stored in the fatty acyl moieties of triacylglycerols. Fatty acids cannot be converted to glucose but the glycerol moiety of triacylglycerol can be converted to glucose but the availability is limited. The other source of glucose is amino acids derived from the breakdown of proteins. Since proteins are not stored in any form the second priority of metabolism in starvation is to preserve protein. Consequently the muscle will shift for fuel from glucose to fatty acids. The oxidation of the fatty acids by muscles halts the conversion of pyruvate into acetyl CoA. (4) During starvation, degraded proteins are not replenished and serve as carbon sources for glucose synthesis. Initial sources of protein are those that turn rapidly such as proteins of the intestinal epithelium and the secretion of the pancreas. During the first 3 days of starvation some muscle protein is degraded and this halt in protein breakdown and loss of muscle mass occurs because of large amount of acetoacetate and Ketone bodies are formed in the liver. (4) After 3 days of starvation, the liver forms large amounts of acetocetate and D-3- hydroxybutyate. Their synthesis from acetyl CoA increase because of the citric acid cycle is unable to oxidize the acetyl units generated by the degradation of fatty acids. In starvation, the body releases protein which is conserved in the part by generation of an alternate energy source namely ketone bodies which are derived from the breakdown of fat. At this time, the brain begins to consume more amount of acetoacetate in place of glucose. About a third of the energy needs of the brain are met by ketone bodies. The heart, kidney and liver also use ketone bodies as fuel. During the first days of starving, the brain continues to use glucose extensively as fuel. In prolonged fasting( greater than 2 or 3 weeks), plasma ketone bodies reach significantly elevated levels and replace glucose as the primary source of fuel for the brain. This reduces the need for protein catabolism for gluconeogenesis. As fasting continues into early starvation and beyond, the kidney plays a very important role. Kidney expresses the enzymes of glucnepgenesis, including glucose 6- Phosphatase and in late fasting about 50% of gluconeogenesis occurs. (1) After several weeks of starvation, the brain uses ketone bodies as a major source of fuel. The effective conversion of fatty acids to ketone bodies by the liver which is used by the brain and other organs markedly diminishes the need for glucose and hence less muscle is degraded as compared to the first days of starvation. A person’s survival time depends upon the size of the triacylglycerol depot. Once the triacylglycerol stores deplete the only other source of fuel is from proteins in the body. Protein degradation accelerates in the body and this induces death inevitably by the loss of liver, kidney or heart function. (1) Works cited 1. Harvey, Richard; Pamela C. Champe and Denise R.Ferrier, Biochemistry; [ed] Nancy Anastasi Dutty, Kathleen Scogna, Baltimore, MD, Lippincott Williams & Wilkins, 2000, 5 (p 307-373) 2. Murray Robert; Daryl K.Granner; Peter A. Mayes and Victor W. Rodwell; Harper’s illustrated biochemistry;[ed] Janet Foltin, Jim Ranson, Janene Matragrano Oransky, united states of America; 2003, 2 (p80-231) 3. Morgan, T.E , FA. Short and L.A Cobb, Effect of long term exercise on skeletal muscle lipid composition, Am J. Physiol, (1969) 216(82-86) 4. Tyoczko John; Lubert Stryer and Jeremy M. Berg; synthesizing the molecules of life: The integration of Metabolism, [Ed] Susan Moran, W. H.Freeman and company, New York, USA (2002) (30.1-30.5) 5. Bryd S.K, L.J. McCutcheon, D.R Hodgson and P.D Gollnick; Equine Exercise Physiology -Ultrastructutral Alterations in Equine Skeletal Muscle Associated with Fatiguing Exercise [ed]S.G.B Persson, A. Lindholm and L.B. Jeffcott Davis, CA, ICEEP , (1991), p269-275 6. Michael Gleeson ‘Biochemical and immunological Markers of over training’ Journal of Sports Science and Medicine, university of Uludag, Turkey,1(2002), p 31-41 7. Edelman Mandle ‘Health Promotion Throughout the life span; Missouri, [ed] Elsevier Mosby; (2006) 8 Nelson L. David, Michael M. Cox, Albert L. Lehninger, Principles of Biochemistry III- Intermediary Metabolism-Integration and Regulation , Palgrave Macmillan Limited( 2004) 9. M.Elia ‘Effect of starvation and very low calorie diets on protein energy interrelationships in lean and obese subjects’ 1991; UN ACC Subcommittee on Nutrition 10. James Loeser; ‘The basics of absorption and metabolism of a meal ‘Aikido World (2000) < http://www.aikido-world.com/articles/Absorption-Metabolism.htm> 11. Tipton M. Charles, ACSM’s advanced exercise physiology [ed] Charles M.Tipton, USA, Lippoincott & Wilkins (2006) , p178-196 12. Martin. H. Wade, Samuel Klein, Proceedings of the Nutrition Society- Used of endogenous Carbohydrate and fat as fuels during exercise, (1998) 57(p 49-54) 13. Coyle F. Edward ‘Fat Metabolism during exercise’ 14. Joanisse R. Denis, ’Functional Metabolism Regulation and Adaptation-Skeletal Muscle Metabolism and Plasticity’ [ed] Kenneth B. Storey. New Jersey, USA, Wiley- Liss (2004), p 295-317 Read More