Nutrition and Metabolism (NUTR 4550) Carbohydrate Regulation PowerPoint 1 Week 1 Notes
Nutrition and Metabolism (NUTR 4550) Carbohydrate Regulation PowerPoint 1 Week 1 Notes NUTR 4550
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This 4 page Class Notes was uploaded by Victoria Hills on Monday January 18, 2016. The Class Notes belongs to NUTR 4550 at Clemson University taught by Dr. Elliot Jesch in Spring 2016. Since its upload, it has received 116 views. For similar materials see Nutrition and Metabolism in Nutrition and Food Sciences at Clemson University.
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Date Created: 01/18/16
Clemson University Spring 2016 Nutrition and Metabolism (NUTR 4550) Unit 1: Regulation Carbohydrate Regulation PowerPoint 1 1/8/2016 Week 1 Slide 1: Figure 12.2 • This slide is looking at insulin and regulation • Glucose is shown in the liver on the left • Liver: -‐ Used for energy storage -‐ One of the locations for energy metabolism -‐ Uses GLUT 2 -‐ The liver is not an insulin dependent tissue for glucose uptake -‐ There are still insulin receptors on the liver that will have signaling, but when insulin is secreted, the liver is not stimulated to take up glucose from a glucose transporter (Meaning the liver can take up glucose via GLUT 2 with or without the presence of insulin) • In any tissue: The first event that occurs when glucose enters the cell is phosphorylation via glucokinase or hexokinase that then converts glucose to glucose-‐6-‐phosphate (This is the first step in glycolysis) • Free glucose means that glucose is not phosphorylated • Sensors on the liver will drive up the activity of hexokinase/glucokinase in order to convert more glucose into glucose-‐6-‐phosphate • When consuming a meal under any circumstances, one is able to consume much more energy at the time of meal than is needed in the body • Example: If you consume a 1000 calorie meal, and 60% of the calories come from carbohydrate, glucose will go into cells and be phosphorylated and continue to be metabolized down to pyruvate (Glycolysis process) • From pyruvate, it is first important to ensure that the cell and tissue has enough energy; Therefore, some pyruvate will be used to make ATP through the TCA cycle and electron transport chain while the rest of the pyruvate will go into storage pathway of fatty acid synthesis (Via pyruvate à Acetyl CoA) • While the excess amount of glucose from the carbohydrate will be stored via fatty acid synthesis, a smaller amount of the excess glucose will be used in glycogenesis for glycogen storage in the liver and muscle cells • Liver glycogen is not depleted often, but it is depleted when an energy deficiency drives the need for glucose utilization -‐ Seen in dieting with low carbohydrate intake -‐ Seen in high intensity exercise that calls for anaerobic respiration, which also requires glucose utilization and will cause the breakdown of liver glycogen -‐ Low intensity exercise is the opposite and will primarily rely on fatty acids as the energy source à Includes walking, jogging, etc. • Pancreas: Insulin effect -‐ GLUT 2 is also used as a glucose transporter so the pancreas and its beta cells must be able to sense glucose flooding in from the diet -‐ Glucose enter the blood stream à Pancreas à Beta cell phosphorylates glucose to glucose-‐6-‐phosphate and produces insulin to be secreted -‐ ATP:ADP ratio increases • Once insulin has been secreted from the pancreas, skeletal muscle and adipose tissue (2 tissues with glucose-‐sensitive transporters) use the GLUT 4 glucose transporter that is sensitive to insulin to take up glucose into the cell to be then phosphorylated to glucose-‐6-‐phosphate via hexokinase/glucokinase • Insulin up regulates glucose phosphorylation • Insulin up regulates fatty acid synthesis as well • Overall: Insulin is an anabolic hormone; therefore, glucose will be converted into fatty acids, glycogen, and insulin will also stimulate the protein synthesis process • Insulin presence plays a small part in glucose going through glycolysis and TCA cycle Slide 2: Figure 12.3-‐ Insulin Metabolism • Figure is showing an overview of insulin and its stimulating of GLUT 4 and glucose uptake in general (In terms of skeletal muscle and adipose tissue, for example) • Top row shows the fed state • Bottom row shows the fasted state • Left column shows the basal state, which is the point where metabolism is steady -‐ The nucleus of the cell produces GLUT 4 -‐ An mRNA transcript is then produced for GLUT 4 in order for it to be translated into a protein -‐ GLUT 4 vesicles are where the GLUT 4 protein is stored within the cytoplasm (This means that GLUT 4 in the vesicle is not functioning as a glucose transporter at this point—It would have to be embedded in the plasma membrane to be an active glucose transporter) • Middle column shows how insulin is present and GLUT 4 moves towards the plasma membrane of the cell • Right column shows that the insulin-‐stimulated cell where the GLUT 4 protein is no longer in the GLUT 4 vesicle and is embedded in the plasma membrane of the skeletal muscle or adipose tissue cells • Fasted State: GLUT 4 mRNA transcript and GLUT 4 translated protein is produced much less than seen in the fed state • Example: Consumption of a carbohydrate-‐rich meal in the fasted state: -‐ There will be trouble transporting the glucose inside the cell -‐ If one continues to fast for a long period of time and then consumes carbohydrate, free glucose will be circulating in the blood and can lead to diabetes -‐ Based on a study, if a person is starved it is important to be cautious about refeeding the person à This may be a reason for the regaining of weight after dieting (Refeeding can lead to excess glucose in the blood and because the body wants to do something with it, results of carbohydrate storage in the form of fatty acids and glycogen Slide 3: Glycolysis • 3 Regulated Steps of Glycolysis: a. Step 1 (Glucose à Glucose-‐6-‐Phosphate via hexokinase/glucokinase) b. Step 3 (Fructose-‐6-‐Phosphateà Fructose-‐1,6-‐bisphosphate via phosphofructokinase-‐1) – (not main regulated step of glycolysis though) c. Step 9 (PEP à Pyruvate via pyruvate kinase) – Involvement of ATP being generated • Points of regulation is in terms of wherever energy is involved • Glycolysis requires the input of ATP at steps 1 and 3 • Glycolysis also produces NADH that will go to the electron transport chain in the step involving glyceraldehyde-‐3-‐phosphate à 1,3-‐bisphoshpoglycerate • Pyruvate has different fates (In terms of energy production): a) TCA Cycle: Occurs because of pyruvate à acetyl CoA via PDH that then enters the TCA cycle (This conversion is a regulated step in metabolism) b) Fatty Acid Synthesis in time of excess: Occurs because of pyruvate à acetyl CoA via PDH c) Anaerobic metabolism: Convert pyruvate to lactic acid -‐ Key to regenerate NAD+ for the step in glycolysis involving glyceraldehyde-‐3-‐phosphate to 1,3-‐bisphosphoglycerate à NAD+ regeneration is important because glycolysis will stop if NAD+ is not regenerated -‐ Also, 2 ATP is produced from (2) pyruvate to lactic acid d) Generation of oxaloacetate via pyruvate carboxylase to keep the TCA cycle running (Having enough oxaloacetate is especially a concern with beta oxidation in the breakdown of fatty acids) • Can funnel in and out different compounds in other pathways in terms of glycolytic intermediates and products Slide 4: Figure 12.5-‐ Fructose and Galactose in Glycolysis • This figure is showing how fructose and galactose are other monosaccharides other than glucose that are able to be incorporated into the glycolytic pathway • Fructose: Can use hexokinase to enter glycolysis as fructose-‐6-‐phosphate and also at the glyceraldehyde-‐3-‐phosphate step • Galactose: Requires a series of steps and enzymes in order to be converted to enter glycolysis as glucose-‐6-‐phosphate -‐ Galactose à Galactose 1-‐phosphate via galactokinase -‐ Galactose 1-‐phosphate à glucose-‐1-‐phosphate via UDP-‐glucose: Galactose 1-‐phosphate uridylyltransferase -‐ Glucose-‐1-‐phosphate à Glucose-‐6-‐phosphate via phosphoglucomutase • Fructose and galactose together make up about 10% of the carbohydrates that a typical American consumes • Glucose makes up about 80 – 90% of the carbohydrates that a typical American consumes • Starch is the majority of carbohydrate that is consumed by Americans Slide 5: Figure 12.6-‐ Gluconeogenesis • Gluconeogenesis is the pathway where glucose is synthesized from non-‐ carbohydrate derivatives (Ex: Seen with the glucose-‐alanine cycle where alanine is converted to pyruvate (alpha keto acid) to be used in the liver to make glucose) • Pathway is used in the fasted state • The primary driver of using glucose is red blood cells (Because they do not have mitochondria so they are entirely anaerobic) and the brain (Can use lipids but has a glucose preference) • Gluconeogenesis is essentially the same pathway as glycolysis but with different enzymes à Although some parts of both pathways overlap, the different enzymes are crucial in making carbohydrate regulation efficient so that glycolysis and gluconeogenesis operate at their appropriate times (Fed vs. fasted states) • Fed State: Applies to glycolysis • Fasted State: Applies to gluconeogenesis • Regulated Steps in Gluconeogenesis: a. Beginning: Pyruvate à Oxaloacetate à PEP b. Fructose-‐1,6-‐bisphoshpate à fructose-‐6-‐phosphate via fructose-‐1,6-‐ bisphosphatase c. Glucose-‐6-‐phosphatase that dephosphorylates glucose-‐6-‐phosphate and yields free glucose
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