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Stephanie HickeyNutrition 445Shearer28 April 2014Case Study 4Obesity: A 19-year-old woman sought medical help because she was 30 kg overweight. Most of her excess weight was in the form of adipose tissue. A medical history revealed that her diet was extremely poor. Much of her caloric intake was carbohydrate – candy, cookies, cake, soft drinks, and beer; her dietary fat intake was actually quite moderate.Questions:How is it possible to form excess amounts of triglyceride in the body if a diet contains predominately carbohydrate?Her diet seems to consist mostly of simple carbohydrates. Simple carbohydrate consists on monosaccharide such as, glucose, fructose, and galactose. Once transport of these monosaccharide’s across the wall of the intestine, they enter the portal circulation, where they are then carried to the liver. During fructose metabolism, fructose can enter the liver pathways. This leads to an increase in fatty acid synthesis, esterification of fatty acids and VLDL secretion which raises the serum of triacylglycerol’s and LDL cholesterol concentrations. Fructose goes through glycolysis through a much faster rate within the liver than does glucose because it avoids the regulatory step catalyzed by phosphofructokinase. Fructose is then converted to the end product of glycolysis, pyruvate. Pyruvate then converts to acetyl-CoA and enters lipogenesis. To begin lipogenesis, acetyl-CoA is converted into malonyl-CoA. Fatty acids that are made from lipogenesis are stored as triglycerides in the adipose tissue. Also, both fructose and galactose can be transformed into glucose derivatives that make them have the same fate as glucose and can be stored as liver glycogen Due to any extra glucose that is not needed for energy or glycogenesis may be transformed into fatty acids. The glycerol that is essential for triacylglycerol is created from triose phosphate. Sent triacylglycerol’s can be formed from glucose, hepatic production is enhanced when the diet is high in carbohydrates. CITATION Gro132 \l 1033 (Gropper & Smith, 2013). (Grooper & Smith, 2013)How does acetyl CoA generated inside the mitochondria reach the cytoplasm for use by the fatty acid biosynthetic pathway?The mitochondria are selectively permeable and acetyl-CoA isn’t permeable to the mitochondria membrane. Almost all of acetyl-CoA that is created in metabolism happens in the mitochondria. It is produced from pyruvate, fatty acid oxidation and degradation of carbon backbone of amino acids through the TCA cycle. Acetyl-CoA is the starter molecule for fatty acid biosynthesis. The synthesis of fatty acids occurs in the cytosol, but acetyl-CoA formed in the mitochondria matrix can’t leave through the mitochondria membrane. So to get acetyl-CoA from the mitochondria into the cytoplasm, a reaction with oxaloacetate to form citrate has to occur because it can pass through the inner membrane. When in the cytosol, citrate lyase transforms citrate back to oxaloacetate and acetyl-CoA CITATION Gro132 \l 1033 (Gropper & Smith, 2013). Figure 2: (Grooper & Smith, 2013)How might the carbohydrate ingested by this patient supply the NADPH needed for fatty acid biosynthesis?The NADPH is formed by the pentose phosphate pathway within the cytosol. One of the important functions of the pathway is the reduced cosubstrate NADPH, which is used for metabolic functions such as fatty acid biosynthesis. The cells of tissues that are active in the synthesis of fatty acids, for example, the mammary gland, adipose tissue, adrenal cortex, and the liver, need NADPH. These tissues recover pentose phosphates back to glucose-6-phosphate to repeat the cycle to ensure there is an abundant supply of NADPH. The pathway reactions that feature the dehydrogenase reactions and the formation of NADPH from NADP+ are the oxidative reaction of the pathway CITATION Gro132 \l 1033 (Gropper & Smith, 2013). Devise a test that would indicate whether this patient could mobilize the triglyceride that is stored in her adipose tissue.Testing the blood or enzymatic activity would indicate whether this patient could mobilize the triglyceride and free fatty acids that is stored in her adipose tissue. Adipose tissue absorbs triacylglycerol’s (TAG) and cholesterol from chylomicrons through the action of lipoprotein lipase (LPL). LPL is used in lipolysis, which is responsible for hydrolyzing TAG into glycerol and three fatty acids. Adipocyte is the major site of storage for triacylglycerol’s. The triacylglycerol’s are constantly in a state of turnover, meaning consistent lipolysis is countered by consistent re-esterification to form triacylglycerol’s. Plasma glycerol levels may be used to indicate the turnover rate of TAG in adipose tissue. Insulin levels may also be used to measure the mobilization of TAG; sent insulin inhibits HSL, which hydrolyzes stored TAG, which results in TAG accumulation. If TAG and FFA are highly concentrated in the blood, lipolysis is happening and TAG is being mobilized from adipose tissue (Gropper & Smith, 2013).Furthermore, a lipid panel should be taken when the patient is fasted because lipolysis occurs in a fasted state. The lipid panel will also check for the activity of the hormone epinephrine, norepinephrine, ACTH, and glucagon that activate HSL CITATION Gro132 \l 1033 (Gropper & Smith, 2013).What kind of unsaturated fatty acid can be synthesized from glucose? What metabolic reactions would be involved in this process?Synthesis of unsaturated fatty acids starts with the synthesis of saturated fatty acids. Asides from essential fatty acids, linoleic and α-linoleic acid, our body has the ability to synthesize fatty acids from simple precursors. Glucose crosses the cell membrane by the GLUT4 transporter and is phosphorylated by hexokinase. Glycolysis converts glucose into glucose-6-phosphate; which eventually results in pyruvate where they are oxidized to acetyl-CoA. Both fat and carbohydrate catabolism meet at acetyl-CoA. In fatty acid synthesis, acetyl-CoA forms into Malonyl-CoA, catalyzed by acetyl-CoA carboxylase. This reaction occurs in the cytosol CITATION Gro132 \l 1033 (Gropper & Smith, 2013). Figure 4: CITATION Gro132 \l 1033 (Gropper & Smith, 2013)Unsaturated fatty acids are made from desaturases. Humans lack Δ12 and Δ15 desaturases, therefore, linoleic acid (18:2 Δ9,12) and α-linolenic acid (18:3 Δ9,12,15) are essential because they create double bonds at these positions. Fatty acid desaturation reaction, palmitate and stearate can be transformed into Δ9 monounsaturated fatty acids, such as, palmitoleic acid and oleic acid. These reactions are catalyzed by mixed-function oxidases. Mixed-function oxidases are where two different substrates are oxidized, the fatty acid and NADPH. Fatty acid is oxidized by the release of hydrogen atoms to create double bonds. Oxygen is the last hydrogen and electron acceptor to make water CITATION Gro132 \l 1033 (Gropper & Smith, 2013).Works CitedGropper, Sareen S., and Jack L. Smith. Advanced Nutrition and Human Metabolism. 6th ed. Belmont: Wadsworth Cengage Learning, 2013. Print. ................
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