NUTR 470 1st Edition Lecture 3Review:• Glycemic index— how we judge food• talked about products ready for absorption• Step one use— energy requirement, active transport• step two— fructose, facilitated diffusion• then we start to use it for metabolismGlucose Metabolism-Glucose (metabolism) provides readily available energy for nearly all tissues-glucose is the only energy sources for red blood cells-glucose is the only energy sources for brain and neuronal cells (except when brain uses ketone bodies during prolonged starvation)-we save glucose for the brain— neurons specifically-Glucose metabolism is associated with many biological functions of various types of cellsPhysiological Role of Glucose-Liver cells• Glucose metabolism in liver cells plays a key role in the control whole body glucose homeostasis• Excessive glucose is converted to lipid through de novo lipogenesis-Pancreatic beta cells• Glucose metabolism couples the secretion of insulin – glucose-stimulated insulin release (GSIR)• Glucose metabolism is associated with the survival (apoptosis) of islet β cells• increase of glucose, increase insulin secretion from beta cells— the two work together to bring glucose concentration back to physiological range-Neurons and astrocytes• Energy sensing (via hypothalamic AMPK)• Glucose homeostasis (pyruvate metabolism) Cytoprotection-Cardiomyocytes• Cytoprotection, cardiac functions-Adipocytes— the ways we can store fat for future use• Lipogenesis, adipogenesisUptake of Glucose-Uptake of glucose usually couples glucose phosphorylation.-Uptake of glucose by cells is the first step after which glucose can be used as energy-generation of glucose-6-phosphateThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.• this is a reaction of transferase, transfers phosphate for ATP-Uptake of glucose is a regulatory step in certain types of cells.• muscles cells need uptake as fast as possible, different cells have different functions• once you have glucose for regulation, have enough because of feeding? yes. If not, than fasting. these are the signals for regulation -Glucose uptake by muscle makes a major contribution to glucose homeostasis.-Uptake of glucose by an individual tissue may be crucial for maintaining whole body glucose homeostasis.-Glucose uptake by tissues other than muscle may have limited roles in regulating glucose homeostasis• 40-60 units of glucose are taken up my muscles -insulin regulation is derived from many factors-muscle responds to insulin action-even the brain is involved contributions-muscle makes the greatest contribution because they respond to many signals from the liver and other organs. However, doesn’t take part of this by itself— other cells influence.Glucose Transporters• glucose UPTAKE— when glucose is transferred from circulation to cells; uptake is the rate determining step for this process; once glucose is in then phosphorylation is the rate determining step-Glucose transporters are necessary for the uptake of glucose by cells.-There are many types of glucose transporters (GLUT1-13).-GLUT2: liver and pancreatic β cells• Hepatocytes -GLUT4: muscle and adipose tissue• Glucose uptake—> transfer glucose from circulation to cells• different transporter, different enzymeSignificance of Glucose Transporters — glucose in circulation -GLUT2• allows rapid uptake or release of glucose by liver and pancreatic β cells• easily goes inside-GLUT4— translocation• GLUT4 is insulin-sensitive• uptake important— rate determining step• in response to insulin• The response of GLUT4 to insulin is crucial for maintaining glucose homeostasis.In Depth GLUT4-GLUT4 Translocation— stimulated by insulin-GLUT4 is bound to the Golgi apparatus.-GLUT4 is brought to the plasma membrane by an ATP-requiring process.-Another ATP-dependent mechanism transports GLUT4 back to the Golgi apparatus where these molecules are once more inactive.-in response to fasting, turn off the translocation so we have enough glucose for the brain-why insulin injections can kill someone— release too much glucose at a time- Video: showing translocation from inside to surfaceType one diabetes importances-only way to treat type one is insulin injections -Type one— insulin injection example, know how its dangerous-trying to achieve homeostasis -GLUT4 Translocation: Role of Insulin-When plasma glucose levels are high, the secretion of insulin is increased, which in turn promotes GLUT4 translocation to cell surface to increase glucose uptake by muscle cells.-When insulin levels fall, GLUT4 is translocated back to the Golgi apparatus. Therefore, glucose uptake is reduced – glucose is spared for important tissues and/or organs, i.e., the brain.-What are the reasons for translocation? — could tell us more about diabetes Glucose Phosphorylation-Hexokinase catalyzes the phosphorylation of glucose-Four isoforms of hexokinase: HKI – IV (hexokinase 1 - 4)-HKII• is presented in nearly all cells. (hexokinase 2)• involved with muscle, adipose tissue-HKIV• is a unique isoform of HK and is referred to as glucokinase.— because glucose is used as a substrate• involved with beta cells• glucose—> uptake —> phosphorylation• so you can have GLUT2 —> GLUT4 (or vice versa)-Always 2-4 or 4-2 pair. -Glucose uptake is easy, then phosphorylation slows it down (rate limiting step)Michaelis-Menten equation-v = vmax [s]/ (Km + [s])-Basic Concepts of Enzyme Kinetics-Km is the substrate concentration at which v is half the maximal velocity (Vmax/2) of the enzyme.• the number will tell you affinity of the substrate binding• high number = not easy to bind; low number = easy to bind -Km indicates the ability of an enzyme in binding a substrate.-Vmax is the maximal velocity of an enzyme. When [S] greatly exceeds Km, the reaction velocity is maximal.-When [S] is in excess, the reaction is determined by Vmax.Modulator of enzyme-An inhibitor can either increase the Km of an enzyme or reduce the Vmax of the reaction catalyzed the enzyme.• inhibitor and activator is based on kinetics• inhibitors making reactions difficult.. slow down-An activator can either reduce the Km of an enzyme or increase the Vmax of the reaction catalyzed the enzyme.-Enzyme Kinetics: Application-Hexokinase II vs. hexokinase IV (glucokinase)•