HNF 461 Exam 1 Study Guide Lectures 1 13 Lecture 1 August 30 ATP Adenosine Triphosphate Source of energy in the body because the bonds between the phosphate groups contain a high amount of energy and that energy is released when bonds are broken ATP is released from macronutrients when they are digested and catabolized Then the ATP is used for energy requiring processes in the body Exothermic Reaction reaction releases ATP goes from high to low energy state o EX metabolism of glucose to pyruvate in glycolysis and the generation of ATP from phosphocreatine in the muscle Endothermic Reaction reaction requires ATP goes from low to high energy state o EX gluconeogenesis Phosphorylation of ADP creates ATP Regulating Enzyme Activity Control of Enzyme Activity o Allosteric Regulation Enzyme reacts with small molecule and changes the composition of the enzyme changes the enzyme activity Does not involve formation of new bonds o De phosphorylation Changing the enzyme s activity by adding or removing a phosphate group Phosphorylation forms a new divalent bond Change in the amount of enzymes o Control of gene expression AMPK AMP activated by a decrease in the cell s energy state increased AMP ATP ratio Activation of AMP Kinase AMPK stimulates processes that produce ATP and inhibit those that use ATP High levels of AMP promotes the phosphorylation of AMPK activates the kinase Then AMP further activates the enzyme by allosterically activating AMPK When AMPK is active it stimulates increased food intake Lecture 2 September 4 Glucose Transporters GLUT 1 3 basal uptake in many tissues very low K m GLUT 2 Liver and pancreatic beta cells high K m GLUT 3 brain very low K m GLUT 4 muscle and adipose tissue regulated by insulin physiological K m o Transports when there is high levels of glucose insulin in the blood Km Levels High Km enzyme requires a high concentration of blood glucose to function at maximum velocity can handle a high concentration of substrate Low Km Enzyme can function at maximum velocity at normal glucose levels can efficiently use glucose Functions of Glucose in the Cells Fuel for ATP synthesis Glycogenesis Synthesis of ribose NADPH and glucose for glycoprotein glycolipid synthesis lower priority Substrate for fatty acid synthesis occurs only in the liver lowest priority Glucose Phosphorylation First step in glycolysis Requires ATP Produces glucose 6 phosphate which is trapped in the cytoplasm Uses hexokinase lower Km in the muscles and glucokinase higher Km in the liver Glycolysis Glucose 6 Phosphate Fructose 6 phosphate reversible reaction Fructose 6 phosphate fructose 1 6 bisphosphate uses 1 ATP Fructose 1 6 bisphosphate DHAP 1 3 bisphosphoglycerate produces 2 NADH PEP 2 pyruvate produces 2 ATP o Under anaerobic conditions pyruvate will be converted to lactate uses 2 NADH Enzymes that Control Glycolysis Hexokinases regulated by glucose concentrations increased glucose increased transport Phosphofructokinase 1 converts fructose 6 phosphatte to fructose 1 6 bisphosphate o Inhibited by ATP activated by AMP o Also regulated by fructose 2 6 bisphosphate which is controlled by PFK2 Pyruvate Kinase Pyruvate Dehydrogenase Process that bridges together glycolysis and the TCA cycle converts pyruvate to acetyl CoA Products of Glycolysis Substrate Level Phosphorylation 2 ATP produced Aerobic Glycolysis 2 NADH produced Anaerobic Glycolysis 0 NADH produced because both are used in the conversion of pyruvate to lactate Lecture 3 September 6 PDH Pyruvate is converted to acetyl CoA TCA Cycle Acetyl CoA is oxidized Generates substrates for fatty acid glucose and amino acid synthesis 1 acetyl CoA produces 2 CO2 3 NADH 1 FADH2 and 1 ATP Electron Transport Chain NADH and FADH2 enter the mitochondrial membrane and are oxidized to produce ATP NADH released from TCA cycle is oxidized to NAD in complex 1 The electron lost from NADH is passed through the chain of complexes FADH2 enters complex 2 and is oxidized to FAD enters in the chain later than NADH so less FAD is produced Hydrogens are pumped into mitochondrial matrix which created a gradient that charges the production of ATP Inhibited by low oxygen supply low ADP and high ATP ATP Production Count Glycolysis produces 2 NADH and 2 ATP PDH produces 2 NADH TCA Cycle produces 6 NADH 2 FADH2 and 2 ATP 2 acetyl CoA TCA cycle TOTAL 10 NADH x 2 5 ATP NADH 2 FADH2 x 1 5 ATP FADH2 4 ATP 32 ATP for 1 glucose Malate Aspartate Shuttle Transports NADH from glycolysis into the mitochondrial matrix Oxaloacetate is reduced by NADH to form malate and NAD Malate is transported to the matrix then converted back to oxaloacetate which causes formation of NADH In another reaction oxaloacetate in the matrix reacts with glutamate to form aspartate Aspartate is then shuttled outside of the mitochondria and converted back to oxaloacetate This reaction ensures that a buildup of oxaloacetate in one area does not occur Glycerol 3 Phosphate Shuttle Occurs in the liver and kidneys after glycolysis Dihyrdoxyacetone phosphate reacts with NADH in the cytosol to form glycerol 3phosphate which then diffuses into the mitochondrial inner membrane In the inner membrane FAD is reduced to FADH2 uses 1 NADH With this shuttle a total of only 30 ATP are produced Brown Adipose Tissue Makes heat during the electron transport chain Contains a higher amount of mitochondria than white adipose tissue Fatty acids are carried to BAT by blood supply and are oxidized to produce heat Lecture 4 September 9 Hexosemonophosphate Shunt Pentose Phosphate Pathway PPP Forms pentose phosphates building blocks for DNA RNA and NADPH for fatty acid synthesis Oxidative Stage oxidizes glucose in two reaction 6 carbon sugar is converted into pentose Releases 1 CO2 and 2 NADPH not reversible Nonoxidative State Sugar molecules exchange carbons between themselves to create new sugars with different arrangements while maintaining the original amount of carbons Riboses are produced reversible Glycogenesis Conversion of glucose to glycogen to store requires ATP Occurs with glucose is abundant and in excess Occurs in the liver and skeletal muscle Helps maintain blood glucose levels Glycogen stored in the liver can be released back into the blood but glycogen stored in muscle must stay in that muscle fiber o Glucose Phosphatase is the enzyme that dephosphorylates glucose so it can reenter the blood enzyme is in the liver but not in the muscles Process GLUT 2 takes glucose out of the blood Glucokinase uses 1 ATP to start