扬州大学：《生物化学 Biochemistry》课程教学课件（讲稿）chapter 13 Glucose metabolism

Glucose metabolism

Glucose metabolism

Glucose occupies a central positionin the metabolismItisamajorsourceofmetabolicenergyItprovidesthe precursorsforthe synthesisof otherbiomoleculesItisstoredinpolymericform(asstarchinplantsandasglycogeninanimals)

Glucose occupies a central position in the metabolism  It is a major source of metabolic energy.  It provides the precursors for the synthesis of other biomolecules.  It is stored in polymeric form (as starch in plants and as glycogen in animals)

Pathways of glucose metabolismGlycolysis“Glyco"_“lysis":breakdownofglucosemonomerGluconeogenesis“New"“genesis"of“glucose":synthesizingglucose“from scratch”Usedwhen supplyofglycogenisexhaustedGlycogensynthesisanddegradationStoringglucoselong-term andrecovering it laterPentosephosphatepathwayUsedtogeneratepentoses(5-Csugars)Startwithglucose

 Glycolysis  “Glyco” – “lysis”: breakdown of glucose monomer  Gluconeogenesis  “New” “genesis” of “glucose”: synthesizing glucose “from scratch”  Used when supply of glycogen is exhausted  Glycogen synthesis and degradation  Storing glucose long-term and recovering it later  Pentose phosphate pathway  Used to generate pentoses (5-C sugars)  Start with glucose Pathways of glucose metabolism

Properties of glucosemetabolism pathwaysEachstepisadifferentchemical reactionand iscatalyzedbyadifferentenzyme.Free energyreleased orconsumed is transferred to carriers likeATPand NADH.Rateof pathwayflux controlled by changingactivity ofindividualenzymes.Multiple steps → greater energy recoveryTwo general purposes of catabolicpathwaysConvert energy inmolecules tomoreusableformCreateintermediatestobeused inotherpathways

 Each step is a different chemical reaction and is catalyzed by a different enzyme.  Free energy released or consumed is transferred to carriers like ATP and NADH.  Rate of pathway flux controlled by changing activity of individual enzymes.  Multiple steps → greater energy recovery.  Two general purposes of catabolic pathways  Convert energy in molecules to more usable form.  Create intermediates to be used in other pathways. Properties of glucose metabolism pathways

MajorPathways of Glucose UtilizationExtracellularmatrixputzoStructuralStorageGlycogen,and cell wallpolymerspolymerspolysaccharidesstarch,sucrosesynthesis of0structuralstoragepolymersGlucoseoxidationviaoxidationviapentosephosphateglycolysispathwayRibose5-phosphatePyruvateBuildingblocksforDNAandRNA

Major Pathways of Glucose Utilization Structural polymers Storage polymers Building blocks for DNA and RNA

KeyprinciplesMetabolites like glucose are often activated with a high-energy groupbeforetheircatabolism.Glucose and other hexoses and hexose phosphates obtained from storedpolysaccharides or dietary carbohydrates feed into the glycolyticpathway.Pyruvateformed under anaerobic conditions is reducedtolactatewithelectrons from NADH, recycling NADH to NAD+ and allowingcontinued glycolysis inthe processes of lactate or alcohol fermentationGluconeogenesis is the synthesisofglucosefrom simpler precursorslikepyruvateandlactate.Glycolysis and gluconeogenesis are reciprocally regulated so that bothprocesses don't occur simultaneously in a futile cycle.The pentosephosphate pathway is an alternativepathwayforglucoseoxidation

 Metabolites like glucose are often activated with a high-energy group before their catabolism.  Glucose and other hexoses and hexose phosphates obtained from stored polysaccharides or dietary carbohydrates feed into the glycolytic pathway.  Pyruvate formed under anaerobic conditions is reduced to lactate with electrons from NADH, recycling NADH to NAD+ and allowing continued glycolysis in the processes of lactate or alcohol fermentation.  Gluconeogenesis is the synthesis of glucose from simpler precursors like pyruvate and lactate.  Glycolysis and gluconeogenesis are reciprocally regulated so that both processes don’t occur simultaneously in a futile cycle.  The pentose phosphate pathway is an alternative pathway for glucose oxidation. Key principles

GlycolysisNet equation:glucose+2NAD*+2ADP+2P-→2pyruvate+2NADH+2ATP1 ×C62 ×C310-stepoxidationpathwaySteps1-5:energyinvestmentphaseSteps 6-10:energypayoff phaseEnzymenametellsyouwhatitdoesRemember structure of glucose, then just follow the steps to gettheotherstructures

 Net equation:  10-step oxidation pathway  Steps 1-5: energy investment phase  Steps 6-10: energy payoff phase  Enzyme name tells you what it does.  Remember structure of glucose, then just follow the steps to get the other structures. Glycolysis 1 ×C6 2 ×C3

Overview of GlycolysisEssentiallyall cells carryout glycolysisTenreactions-sameinallcells-butratesdifferTwo steps:First step converts glucose to two glyceraldehyde-3-phosphateSecondstepproducestwopyruvates（丙酮酸）Products are pyruvate, ATP and NADHThreepossiblefatesforpyruvate

Overview of Glycolysis  Essentially all cells carry out glycolysis  Ten reactions - same in all cells - but rates differ  Two steps:  First step converts glucose to two glyceraldehyde-3-phosphate.  Second step produces two pyruvates（丙酮酸）  Products are pyruvate, ATP and NADH  Three possible fates for pyruvate

Biologicalimportance of glycolysisItcanfunctionaerobicallyoranaerobically,dependingontheavailabilitof oxygen and electron transport chain (ETC).Some special cells have nomitochondria and they rely completely on glucose as their metabolic fuelandmetabolizeitanaerobically.Glycolysis is the principle route for glucose metabolism, and is also themain pathway for the metabolism of fructose, galactose and other sugarsderivedfromthediet.GlycolysisofglucosetoprovideATPanaerobicallyisespeciallyimportant, because skeletal muscles can perform under anoxic conditions[e'npksik]缺氧的In the cancerous cells glycolysis proceeds at a very high rate, forminglarge amounts of pyruvate, which is reduced to lactate,leads to acidicenvironment and has implications for cancer therapy

Biological importance of glycolysis  It can function aerobically or anaerobically, depending on the availability of oxygen and electron transport chain (ETC). Some special cells have no mitochondria and they rely completely on glucose as their metabolic fuel and metabolize it anaerobically.  Glycolysis is the principle route for glucose metabolism, and is also the main pathway for the metabolism of fructose, galactose and other sugars derived from the diet.  Glycolysis of glucose to provide ATP anaerobically is especially important, because skeletal muscles can perform under anoxic conditions.  In the cancerous cells glycolysis proceeds at a very high rate, forming large amounts of pyruvate, which is reduced to lactate, leads to acidic environment and has implications for cancer therapy. [əˈnɒksɪk] 缺氧的

Free energy changes in glycolysisGlucoseLargenegative △G-16.7kj/molmetabolicallyirreversible17.2kj/mol0-16kj/molPyruvateThreestepshavelargenegativevaluesofAGThese stepsarepotentialflux-controlpointsSlower steps-pathway can only go as far as its slowest step

Free energy changes in glycolysis  Three steps have large negative values of ΔG.  These steps are potential flux-control points.  Slower steps-pathway can only go as far as its slowest step