Dyslipidemia Nonalcoholic Fat Liver Disease -Myassignmenthelp.Com

Question: Discuss About The Dyslipidemia Nonalcoholic Fat Liver Disease? Answer: Introduction The purpose of digestion, absorption and metabolism of carbohydrate is to break down the complex bio-molecules into simple glucose. Glucose is the primary source of fuel within the body. The overall rate of carbohydrate digestion and absorption is dependent upon the rate of breakdown of the glucose. The pancreases and liver plays significant role on the metabolic activity of glucose secretion of essential enzymes. Glycolysis Glycolysis is the first step in the process of carbohydrate metabolism, where the glucose molecule is broken down into pyruvate, which is a three carbon molecule. In the due process energy is formed within the body in the forms of ATP. There are ten steps within the process of glycolysis that take place within the cytosol of the cell. The entire process can be broken down into two phase. In the preparatory phase (first 5 steps) energy is consumed to convert glucose to 2 3-C sugar phosphates. C6H12O6 + 2 NAD+ + 2 ADP + 2 P ----- 2 pyruvic acid, (CH3(C=O)COOH + 2 ATP + 2 NADH + 2 H+ The next phase of the carbohydrate metabolism is the pay-off phase, where ATP is being produced as the glucose molecule is being converted to pyruvate. This explains the breakdown of carbohydrate rich meals consumed by John. The Citric acid Cycle The pyruvate so formed has different fate depending upon the presence or the absence of oxygen. It includes a series of chemical reactions that are used to release energy through acetyl CoA oxidation that is derived from fats, carbohydrates and proteins. Pyruvate is converted to Acetyl CoA that enters the citric acid cycle, and in a series of chemical reaction, chemical energy is released in the form of ATP. Thus, the cycle demonstrates how the end products of fat and carbohydrate rich compounds consumed by John produce energy. Gluconeogenesis This process results in production of glucose from non-carbohydrate substrates, such as, lactate, glycerol, especially during fasting. This process is extremely important tormenting the minimum blood glucose level. Lactate is converted to pyruvate through Cori cycle, using lactate dehydrogenase. Pyruvate is then converted back to glucose in almost entire backward process of glycolysis. Hence, in other words it can be said that gluconeogenesis is the reversal metabolic pathway of glycolysis. Electron Transport chain Electron transport chain consists of a series of complexes that help in transferring electrons in inner mitochondrial membrane. It releases the stored energy in the form of reduced hydrogen, which is used to generate ATP from the process of oxidative phosphorylation. Following are the steps followed in electron transport chain and oxidative phosphorylation Electron carriers in the form of NADH and FADH2, transfer that electron at the beginning of the chain. Electron move through the chain, from higher potential gradient to lower energy level, which releases energy in the form of hydrogen ions, creating an electrochemical gradient. At terminal point of the transport chain, oxygen accepts the electron, which splits up the hydrogen ion thereby forming water molecule. H+ flows down the gradient back to the matrix, where they are catalysed with the enzyme ATP synthase. Oxidative Phosphorylation It produces most energy of cellular respiration where electron transport from TCA cycle precursors phosphorylates ADP, producing ATP. Hydrogen flow in ETC powers ATP synthase, to produce ATP. This explains cellular respiration in the case scenario. Figure: Electron Transport Chain and Oxidative Phosphorylation Beta-oxidation It refers to the catabolic process of breaking down fatty acid molecules in prokaryotes (cytosol) and eukaryotes (mitochondria), thereby generating acetyl-CoA molecules. The Acetyl CoA enters the TCA. FADH2 and NADH are also produced in the pathway that are utilised by the ETC. It encompasses oxidation of the carbon to acarbonylgroup. The pathway facilitated by amitochondrial tri-functional protein, and an inner mitochondrial membrane enzyme complex. It can be represented by the following equation- Cn-acyl CoA + FAD +NAD++H2O+ CoA Cn-2-acyl CoA +FADH2+ NADH +H+ + acetyl CoA The major steps involved in the pathway include activation and transport of FFA across membranes by binding to CoA, oxidation of the carbon, carbon segment cleavage, acetyl CoA oxidation to CO2 and electron transfer. This pathway can therefore be used to demonstrate oxidation of the fats that are present in fried foods consumed by John. It is evident from the case scenario that John consumes carbohydrate rich meals and junk food that are rich in unhealthy fats and refined carbohydrates. His feeding habits have contributed to the overweight by creating an energy imbalance between the calories that he consumes and the amount that is expended. Excess accumulation of fats and sugars in the body has resulted in weight gain. Furthermore, research evidences establish the fact that the hormone insulin is responsible for regulating blood sugar levels in the body by signalling the muscle, liver and ft cells to absorb glucose from blood. Upon ingestion of carbohydrates, insulin is produced by the cells of islets of langerhans that enhance entry of glucose into all tissues and increase production of enzymes that are essential for glycolysis. Owing to the fact that glycolysis is controlled by the blood glucose concentration, action of insulin stimulates glycolysis, thereby lowering the blood glucose levels (Guo et al., 2012). Presence of insulin resistant cells in the body results in failure to uptake amino acids, glucose and fatty acids. A reduction in the insulin/glucagon ratio results in inhibition of glycolysis, thereby decreasing energy production. Research findings establish the fact that consumption of processed and fried foods lead to insulin resistance. This contributes to Johns likelihood of developing diabetes. Obesity and susceptibility to diabetes can be correlated based on the action of overeating on the membranous networks of endoplasmic reticulum. Presence of more processed food makes the ER send an alarm to inhibit the cell surface insulin receptors. This gets translated to insulin resistance and leads to persistent high levels of glucose in the body, causing diabetes. Increase in body weight leads to expansion of visceral adipose tissue that down-regulates insulin levels. Owing to the primary function of insulin signalling in suppression of lipolysis (fatty acid chain removal), insulin r esistance in the adipose tissues are often correlated with increased levels of free fatty acids, thereby contributing to elevated hepatic triglyceride generation. Due to overconsumption of processed and fried foods, an imbalance is created between the uptake of fatty acids and beta-oxidation, which directly contributes to insulin resistance in the muscles. Lipid accumulation results in inhibition of few steps in the insulin signalling cascade (Jung Choi, 2014). A thorough study of the aforementioned case scenario suggests that free fatty acids in the bloodstream, due to incorrect eating habits form the association between his obesity, and risk of developing diabetes due to insulin resistance. Consuming fat and carbohydrate rich food products result in increase in malonyl-CoA in the liver that inhibits CPT1 and fatty acid oxidation. Accumulation of fats in the muscle eventually led to increased levels of beta oxidation that reduces activity of the citric acid cycle. Thus, the products formed due to incomplete beta oxidation (ROS and acylcarnitines) activate stress induced kinases that create insulin resistance. Furthermore, fried foods also create a significant burden on the digestive system. Thus, increased intake of carbohydrate and calorie rich food, exhibited by John keeps him at an increased likelihood of acquiring diabetes. This might directly result in a spike in blood sugar levels. Reference Guo, X., Li, H., Xu, H., Woo, S., Dong, H., Lu, F., ... Wu, C. (2012). Glycolysis in the control of blood glucose homeostasis.Acta Pharmaceutica Sinica B,2(4), 358-367. Jung, U. J., Choi, M. S. (2014). Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease.International journal of molecular sciences,15(4), 6184-6223.