Metabolic Pathways
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3. Use Arial font, size 11, 1Humans require approximately 2000 kcal per day. For an untreated diabetic with no access to insulin, whose body is dependent on triglycerides, outline how the energy in triglycerides becomes available to the patient. Specifically, describe the diet, digestion and absorption and degradation pathways that create energy and ketone bodies.
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The following questions provide problem-solving scenarios that focus on either carbohydrate, protein or lipid metabolism. You are required to answer in detail, as outlined in the Task-specific guidelines, using clear and concise, scientific English. References are included to assist with your research and writing in scientific English your writing style and research technique. Please read and follow the Marking guide carefully to understand the assessment criteria.
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Humans require approximately 2000 kcal per day. For an untreated diabetic with no access to insulin, whose body is dependent on triglycerides, outline how the energy in triglycerides becomes available to the patient. Specifically, describe the diet, digestion and absorption and degradation pathways that create energy and ketone bodies.
I. Explain the metabolic pathways in which lipid metabolism leads to energy and low level ketone body production in the cells, following a triglyceride-rich meal.
II. Briefly describe excessive catabolism of lipids.
III.Explain why untreated diabetics have an insufficient oxaloacetate supply, which is needed to derive energy from lipids.
Solution
Metabolic Pathways
Humans require approximately 2000 kcal per day. For an untreated diabetic with no access to insulin, whose body is dependent on triglycerides, outline how the energy in triglycerides becomes available to the patient. Specifically, describe the diet, digestion and absorption and degradation pathways that create energy and ketone bodies.
I. Explain the metabolic pathways in which lipid metabolism leads to energy and low level ketone body production in the cells, following a triglyceride-rich meal.
After the consumption of a triglyceride-rich meal, the dietary lipids are assembled into chylomicrons for transportation to the blood by the lymphatic system occurs, leading to the secretion of insulin for the regulation of fuel consumption. Insulin and glucagon act as fuel metabolism regulators. Insulin initiates protein kinase cascades, suppresses gluconeogenesis, and accelerates glycolysis in the liver increasing fatty acids synthesis. The metabolism of triacylglycerol provides ATP in a process that starts with the esterification of fatty acids with glycerol for the formation of triacylglycerol which is stored in the adipose tissue. The oxidation of the consumed meal’s components, in this case fatty acids, occurs in three metabolic pathways. These pathways include the B-oxidation pathway, the respiratory chain, and the Krebs cycle. As Salway (2013) describes the process, it starts with the liberation of fatty acids from the triacylglycerol by the hormone sensitive lipase from the adipose tissue.
The beta-oxidation metabolic pathway involves the breaking down of fatty acids by numerous body tissues for the production of ATP energy. The process starts with the entry of the fatty acids into the cell facilitated by the protein transporters of the fatty acid that exist on the surface of the cell. These transporters include fatty acid transport proteins, CD36/fatty acid translocase, and the binding proteins bound by the plasma membrane (Black, Sandoval, Arias-Barrau, & DiRusso, 2009). The entry allows the addition of the CoA group to the fatty acid by the fatty acyl-CoA synthase for the formation of the acyl-CoA. The acyl-CoA is a long-chain component that is converted to a long-chain acyl-carnitine by the carnitine palmitoyltransferase 1 (CPT1) making the transportation of the fatty acid over the inner membrane of the mitochondrion through the carnitine-acylcarnitine translocase (CACT) (Black, et al., 2009). The conversion of the long-chain acyl-carnitine occurs to re-form the long-chain acyl-CoA, which enters the beta-oxidation pathway causing the production of a single acetyl-CoA. The production of ATP occurs from the use of the FADH2 and the NADH after the entry of the acetyl-CoA into the mitochondrial tricarboxylic acid.
From the beta-oxidation pathway, the molecules of acetyl-CoA enter the Krebs cycle where oxidation takes place. The production of ATP occurs with the formation of NADH and FADH2 by the cycle and from the beta-oxidation. Salway (2013) states that the Krebs cycle paves way for the occurrence of the respiratory chain. This results in the production of a significant amount of ATP. In the respiratory chain metabolism pathway, the oxidation of NADH and FADH2 produced from the initial steps of Krebs cycle and the B-oxidation takes place causing the production of ATP through oxidative phosphorylation (Veleba, et al., 2015). In this scenario, the consumption of triglyceride-rich meal provides sufficient supply of fatty acids preventing the occurrence of ketogenesis but enabling the utilization of the food components in the production of ATP (Salway, 2013). Therefore, in this case, there is a low production of ketone bodies since ketogenesis occurs when the body is at a state of low availability of carbohydrates, which triggers the breaking down of fat to acetyl-CoA for energy.
II. Explain why untreated diabetics have an insufficient oxaloacetate supply, which is needed to derive energy from lipids.
Diabetics have an insufficient supply of oxaloacetate due to the removal of oxaloacetate from the mitochondrion for gluconeogenesis. The process of fatty acid metabolism in healthy people involves the formation of fatty acids during the process of lipolysis by the adipose tissue. The fatty acids commence and undergo a cyclic process that includes re-esterification with glycerol 3-phosphate and the re-formation of triacylglycerol. However, the case is different in people suffering from diabetes. The cyclic process in diabetics is interrupted by the unavailability of or the insufficiency of glycerol 3-phosphate because it is formed from glucose and requires sufficient insulin to enter the fat cells (Veleba, et al., 2015). The inability of the diabetics’ body to release glycerol 3-phosphate occurs due to the inability of their bodies to produce sufficient insulin. Diabetes impairs the production or response to the production of insulin by the body, which results in abnormalities in the process of carbohydrates’ metabolism (Salway, 2013). The process leads to increased levels of glucose in the persons’ urine and blood. The production and use of glycerol 3-phosphate in the process of re-forming triacylglycerol in people suffering from diabetes is inhibited by the inability of their bodies to produce sufficient insulin (Salway, 2013).
Decreased re-esterification of fatty acids in diabetics causes their release into the blood. In people without the disease, the oxidation of fatty acids causes energy for respiratory in different tissues especially the red skeletal muscles. However, in diabetics, the body holds surplus fatty acids that are then transported to the liver for entry into the B-oxidation spiral for the formation of acetyl-CoA (Salway, 2013). While in healthy people the condensation with oxaloacetate allows oxidation in the Krebs cycle, oxaloacetate is removed from the mitochondrion for the process of gluconeogenesis causing its shortage in people suffering from diabetes. Untreated diabetics have an insufficient supply of the oxaloacetate because of the inability to produce insulin, which results in the incapability of the glycerol 3-phosphate to enter fat cells and the removal of the oxaloacetate from the mitochondrion for gluconeogenesis (Salway, 2013).
II. Briefly describe excessive catabolism of lipids.
The beta-oxidative
pathway catabolises lipids in the mitochondrial matrix as explained in the discussion
of the pathways in question one. However, in certain scenarios, excessive
catabolism occurs. According to Black, et al. (2009), the process of
metabolism of fatty acid comprises of different processes for the generation of
energy and the creation of essential molecules. Excessive catabolism of the lipids
leads to the depletion of the available lipid components for the production of
energy. This results in the development of ketogenesis, which causes an
increase in ketone bodies production. The process leads to gluconeogenesis which
depletes the oxaloacetate in the liver and inhibits the entry of acetyl-CoA in
the Krebs cycle. The scenario occurs in a similar way as of a fasting person or
a diabetic. The liver mitochondria converts the acetyl-CoA into ketone bodies (Salway, 2013; Veleba, et al., 2015).
The continued metabolism may result in ketoacidosis and catabolic disease,
which may involve rapid loss of fat, weight, and skeletal muscle mass.
References
Black, P. N., Sandoval, A., Arias-Barrau, E., & DiRusso, C. C. (2009). Targeting the fatty acid transport proteins (FATP) to understand the mechanisms linking fatty acid transport to metabolism. Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry, 9 (1), 11–17.
Salway, J. G. (2013). Metabolism at a glance. Malden, Mass.: Blackwell Pub.
Veleba, J., Kopecky Jr., J., Janovska, P., Kuda, O., Horakova, O., Malinska, H., & Fiserova, E. (2015). Combined intervention with pioglitazone and n-3 fatty acids in metformin-treated type 2 diabetic patients: improvement of lipid metabolism. Nutrition & Metabolism, 12, 1-15.
