HNF 461 Exam 2 Study Guide Lectures 14 27 Lecture 14 October 2 Glucose Uptake 1 Glucose Absorption into the Small Intestine a Na dependent transporter requires ATP b GLUT2 transporter c With high glucose in the intestinal lumen the GLUT2 pathway is dominant 2 Insulin Regulation of Intestinal Glucose Absorption a Insulin receptors located on cell membranes b Insulin binds to receptor which triggers the translocation of GLUT4 from vesicles inside the muscle adipose cells to the cell membrane c Insulin also controls blood glucose levels by inhibiting glucose intake in the intestine inhibits function of GLUT2 3 Km Values a The value of substrate glucose that is needed in order to reach half of the maximum enzyme activity b GLUT1 3 very low Km basal uptake in cells brain cells cells need a constant supply of glucose c GLUT2 high Km liver pancreatic beta cells and enterocytes cells respond most efficiently to large concentrations d GLUT4 physiological Km muscle and adipose tissue glucose transport closely follows the amount of glucose in the blood 4 Absorption of Glucose Fructose and Galactose in the Liver a Glucose and Galactose i Na dependent transporter requires energy active transport ii GLUT2 transporter does not require energy facilitated diffusion iii The liver removes galactose from the blood iv The liver removes some glucose from the blood but most stays in the blood and is transported to various tissues organs b Fructose i GLUT5 transporter facilitated diffusion ii The liver removes fructose from the blood 5 GLUT4 a Found in muscle and adipose tissue b Regulated by insulin which regulates its location in the cells Lecture 15 October 7 Diabetes Hypoglycemia and Alcohol 1 Diabetes a Type I Autoimmune disease that destroys beta cells in the pancreas so that it cannot produce insulin i Actions of glucagon and glucocorticoids are unopposed ii Can cause hyperglycemia ketoacidosis and excess urination b Type II The insulin resistance of insulin receptors i Caused by genetic and environmental factors ii Resistance begins in the muscle then progresses to the liver 2 Conversion of Glucose a 5mM glucose 90 mg dL 3 Diagnoses of Diabetes and Prediabetes a Diabetes i Impaired fasting glucose greater than or equal to 126 mg dL ii Impaired glucose tolerance after eating greater than or equal to 200 mg dL b Prediabetes i Fasting glucose 100 125 mg dL ii Post glucose consumption 140 199 mg dL 4 HBA1C a Measures the amount of glycated hemoglobin sugar bound to hemoglobin b Indicator of long term glucose levels i Indicator of glucose levels of the past months ii Measures the amount of glucose residue attached to hemoglobin which does not depend on the short term 5 Type II Diabetes and Obesity a Being overweight can increase the risk of your body becoming resistant to insulin 6 Progression of Type II Diabetes a Insulin resistance in muscle tissue increases blood glucose levels liver produces more insulin adipocyte intake increases increased lipid storage b Liver becomes resistant to insulin more glucose accumulates in blood which increases insulin production over production of insulin eventually causes beta cells to fail 7 Prevention of Type II Diabetes a Prevent limit muscle insulin resistance b Prevent obesity weight loss c Exercise d Consumption of complex carbohydrates legumes whole grains low glycemic index foods with a lot of dietary fiber 8 Metabolism of Alcohol a Two step oxidation process i Oxidation of ethanol acetaldehyde by ADH NAD oxidized to NADH ii Oxidation of acetaldehyde to acetate by ALDH NAD oxidized to NADH b Microsomal Ethanol Oxidizing System MEOS i Occurs in microsomes when alcohol intake is high ii Yields H2O instead of NADH contributes less energy 9 Consequences of Alcohol Intake a NADH NAD Ratio Increases the ratio which can cause hypoglycemia i Lactate cannot be converted to pyruvate lack of pyruvate in the cells so conversion of glucose slows ii Inhibits fatty acid oxidation which causes fat build up in the liver Lecture 16 October 9 Lipolysis Fatty Acid Oxidation and Ketogenesis 1 Hormone Sensitive Lipase HSL a Located in adipose cells b Hydrolyzes triglycerides to yield nonesterified fatty acids NEFA c Activated by glucagon and epinephrine i Glucagon binds to receoptor increases cAMP increases PKA phosphorylation activation of HSL d Inhibited by insulin 2 NEFA Transport a Carried by albumin in blood to tissues for oxidation 3 Energy for Resting Muscles a In post absorptive and at rest muscles use NEFA for energy b Muscle cells take up NEFA converted to Fatty acid CoA in the cell cytoplasm and then is transported to the mitochondria by carnitine 4 Carnitine Shuttle a Shuttles fatty acids across inner mitochondrial membrane i FA CoA binds to carnitine in the cytoplasm by CAT1 enzyme ii CAT2 enzyme releases FA CoA into mitochondrial matrix b Regulation by Malonyl CoA i Malonyl CoA inhibits the CAT1 enzyme converts FACoA to CoA 1 Fatty acid synthesis is increased when there are increased levels of malonyl CoA in the blood during FA synthesis the body does not want to oxidize FAs counterproductive 2 Malonyl CoA will shut down the carnitine shuttle to prevent the break down of fatty acids during fatty acid synthesis 5 Beta Oxidation of Fatty Acids a Produces acetyl CoA FADH and NADH i Acetyl CoA enters Krebs Cycle and generates CO2 NADH FADH and GTP ii If oxygen is present FADH and NADH enter the ETC to produce ATP b Occurs within the mitochondria c FAs are transported into the mitochondria by the carnitine shuttle 6 Ketone Bodies a Compounds formed in the liver during the oxidation of NEFA b Ketones are water soluble transported from the liver to muscle and brain for oxidation oxidized to acetyl CoA which is used for TCA and ETC c Ketogenesis occurs during starvation state to spare glucose with low CHO diet and in diabetes i Production of acetoacetate beta hydroxybutyrate and a small amount of acetone 7 Ketosis a Excess production of ketones caused by high plasma NEFA b Excess ketones causes the blood to because more acidic c Ketones in urine increase urine output and loss of electrolytes 8 Ketoacidosis a Occurs when the body s buffer systems lung and kidney fail and so blood becomes more acidic b Diabetics are at risk because fat cells are unresponsive to insulin glycolysis will not occur and so the level of fatty acids in the blood will rise i Diabetes insulin resistance uncontrolled lipolysis in fat tissue 1 Insulin inhibition of HSL will not occur so a large