CHEM 360 1st Edition Lecture 15Outline of Last Lecture I. MetabolismII. ATP as the universal currency of free energyIII. Coupled ReactionsIV. Activated carriersV. Regulation of metabolic processesOutline of Current Lecture I. Glycolysisa. First phase - Reactions 1-5 (no ATP generated)b. Second Phase – Reactions 6-10 (generation of ATP)II. Feeder pathway to glycolysis (other sugars can also enter the glycolytic pathway)III. Regulation of glycolysisIV. Glucose transportersV. Fate of pyruvate under anaerobic conditionsa. In yeast: Alcohol fermentationb. In other microorganisms and exercising muscle: Lactic acid fermentationVI. Hypoxia-Inducible FactorCurrent LectureRegulation of Glucose Metabolism-Insulin -- increases glycolysisRegulation of Metabolic Pathways-Phosphorylation of an enzyme normally turns off the activity of the enzymeoBut it is a reversible process so when the phosphoryl group is removed the enzyme will become active againSteady-State Flow of Metabolic Pathways: flux-Can think of metabolic pathways like the lined up champagne glasses, the rate of this action depends on the first glassReciprocal Pathways-Glycolysis and gluconeogenesis are examples of reciprocal pathways-If turn off enzyme that converts E --> D then B will convert more to C and F will increaseoAnd the opposite effect will increase AThe energy status of the cell is often an important regulator of enzyme activity-[ATP] > [AMP] = high energy charge-[AMP] > [ATP] = low energy chargeThese 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.-Due to the fact that there are two high energy bonds in ATPEnergy charge regulates metabolism-Energy charge is normally constant at 0.9 which can be seen on the graphMetabolic pathways are compartmentalized within cells-Glycolysis is used both in eukaryotes and prokaryotes-There are ten steps in glycolysis-Use 2 ATP initially-During second phase is where 4 molecules of ATP is generated along with 2 NADH1st Stage of Glycolysis-Phosphorylation of glucose and second phosphorylation of fructose-6P are the regulatedsteps and are irreversibleGlycolysis: Reaction 1 - Phosphorylation-Where first ATP comes in and is usedHexokinase-When a substrate binds to hexokinase it changes its conformationGlycolysis: Reaction 2 - Isomerization by phosphoglucose isomerase-All of these steps are fully reversibleGlycolysis: Reaction 3-Second Phosphorylation-This is the committed step of glycolysis-The enzyme of the committed step is Phosphofructokinase -- determines the rate of glycolysis and this step is irreversibleGlycolysis Reaction 6 - GAP is oxidized to 1,3-BPG-(1,4-BPG) --- means high phosphoryl group transfer potentialoPrecursor to 2,3 BPG in RBC Coupling of the two processes (by one enzyme) allows the conservation of energy released by oxidation-Left graph - uncoupled processesoLeft also involves an acid -Right graph - coupled processesThe free energies of the reactions of glycolysis under actual intracellular conditions in erythrocytes-Means that these three steps are irreversible due to their very negative delta-GsFructose enters the glycolytic pathway in the liver through the fructose 1-phosphate pathway-Don't have to remember any of the enzymesFructose can be converted to F-6P by hexokinase-Hexokinase is only present in adipose tissue??Regulation of glycolysis-PFK/PFK-1 -- The pacemaker of glycolysis, the committed stepRegulation of Allosteric Enzymes by Feedback Mechanism-Intermediates upstream of A --- to the leftoWill activate the committed step or the enzyme that you are talking about-Intermediates downstream of A --- to the rightoWill inhibit the committed step or the enzyme that you are talking aboutRegulation of Phosphofructokinase-There is a muscle version of the enzyme and a liver version of the