最新北大生化课件14 (2)精品课件.ppt

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1、lThe anaerobic breakdown (fermentation) of glucose to ethanol and CO2 by yeast has been exploited for many centuries in baking and winemaking.lScientific investigation of the chemistry of glucose breakdown began in the mid-19th century.lThe complete pathway was described around 1940.(Present in all

2、cells of all organisms)Mg2+ATP2- is the actual substrateAn exergonic group An exergonic group transferring reactiontransferring reaction己糖激酶己糖激酶Hexokinase Hexokinase exhibits exhibits induced induced fitfit property: The binding property: The binding of of glucoseglucose in the active site in the ac

3、tive sitecauses a major conformationalcauses a major conformationalchange.change.Inactive conformationInactive conformationActive conformationActive conformationGlucoseGlucoseSubstrate-induced cleftclosing is a general featureof all kinases!A reversible Isomerization reaction A reversible Isomerizat

4、ion reaction (intramolecular redox reaction)An aldoseA ketose磷酸己糖异构酶磷酸己糖异构酶A necessary prelude for the next two steps ofreactions (phosphorylation and C-C cleavage).Another exergonic groupAnother exergonic grouptransferring reactiontransferring reaction(PFK-1)(PFK-1)磷酸果糖激酶磷酸果糖激酶-1 -1The “lysis” step

5、The “lysis” step123456醛缩酶醛缩酶(C3 or C4)(C5 or C2)(C1 or C6)Other hexoses (e.g., Fru.,Man., Gal.) are alsoconverted to glyceraldehyde3-phosphate to enter glycolysis.A reversible Isomerization reactionA reversible Isomerization reaction (intramolecular redox reaction)磷酸丙糖异构酶磷酸丙糖异构酶An aldoseA ketoseOxid

6、ation (dehydrogenation)Oxidation (dehydrogenation) followed by followed by phosphorolysis phosphorolysis An acyl phosphateAn acyl phosphate(a type of anhydride)(a type of anhydride)3-3-磷酸甘油醛脱氢酶磷酸甘油醛脱氢酶Tetrameric OxidationOxidationstepstepPhosphorolysisPhosphorolysisstepstep( (An acyl-enzyme intermed

7、iateAn acyl-enzyme intermediate) )Inactivation of the enzymeInactivation of the enzymeNADH exchanged NADH exchanged for NADfor NAD+ +3-3-磷酸甘油醛脱氢酶磷酸甘油醛脱氢酶 HB:BHBHB(This enzyme was named for the reverse reaction)substrate-level phosphorylationsubstrate-level phosphorylation( (vs. respiration-linked ph

8、osphorylationvs. respiration-linked phosphorylation) )磷酸甘油酸激酶磷酸甘油酸激酶ADPADPATPATP磷酸甘油酸变位酶磷酸甘油酸变位酶Mutase: catalyzes group transferring from one position to another in a molecule.Phosphoglucomutase acts in a similar fashion!(Initially phosphorylated by using 2,3-BPG)A super high-energy A super high-ene

9、rgy phosphate compoundphosphate compoundDG0 for the hydrolysis of the phosphate group is changed from 17.6 to 61.9 kJ/mol.烯醇酶烯醇酶A Redistribution of energyA Redistribution of energy(PEP)This enzyme was alsonamed for the reverse reactionNonenzymaticconversion丙酮酸激酶丙酮酸激酶ADPADPATPATPThe second substrate-

10、level ADP The second substrate-level ADP phosphorylation!phosphorylation!Major catabolic Major catabolic fates of pyruvatefates of pyruvatePyruvate also actsPyruvate also actsas precursors inas precursors inmany anabolic many anabolic reactionsreactions. . Glucose is activated Glucose is activated (

11、or primed), with (or primed), with 2 ATP molecules 2 ATP molecules invested. invested.primingprimingprimingprimingisomerizationisomerizationcleavagecleavageOnly 5% of thepotential energy of the glucose molecule is releasedduring glycolysis.All the enzymes catalyzing glycolysishave been found in the

12、cytosol. The net production of ATP per glucose inglycolysis is 4-2=2.lWhen proteins are purified from extracts of broken cells in diluted solutions, noncovalent interactions between proteins could be destroyed (i.e., higher level organization destroyed).lKinetic and physical evidences suggest that t

13、he enzymes act to catalyze the ten reactions of glycolysis pathway (as enzymes act in other metabolic pathways) may assemble into multienzyme complexes, where intermediates are directly channeled from one enzyme to another, without entering the aqueous solutions, a phenomenon called “substrate chann

14、eling”.The glycolyticThe glycolyticenzymes very likelyenzymes very likelyform multienzymeform plexes.SubstrateSubstratechannelingchannelingDilutionDilutiondissociationdissociationPyruvate is reducedto lactate, leading toNAD+ regenerationwhen O2 lacks (thusallowing glycolysis to continue);occurring i

15、n very active skeleton muscle, some bacteria like lactobacilliLactic acid Fermentation:乳酸脱氢酶乳酸脱氢酶Present only in those alcohol fermentativeOrganismsPresent in many organisms including humanPyruvate be decarboxylatedPyruvate be decarboxylatedand reduced to form and reduced to form ethanolethanolin so

16、me microorganismsin some microorganismsEthanol Fermentation:丙酮酸脱羧酶丙酮酸脱羧酶乙醇脱氢酶乙醇脱氢酶Thiamine pyrophosphate(TPP) is involved in the cleavage of C-C bondsadjacent to a carbonylgroup. Vitamin B1 (thiamine) is used to synthesize TPP.A lack of Vitamin B1 in humans will result in a condition known as Beribe

17、rilPolysaccharides such as starch and glycogen are first degraded into glucoses via hydrolysis in extracellular spaces (catalyzed by a-amylases and other enzymes), but into glucose 1-phosphate via phosphorolysis inside cells (catalyzed by phosphorylases).lOligosaccharides (e.g., sucrose, lactose, tr

18、ehalose etc) are degraded into monosaccharides before further transformed.lHexoses other than glucose can also be catabolized via the glycolytic pathway after being converted to a phosphorylated derivative.To counter the damagingeffects of oxygen radicalsFor Reductive biosynthesisNucleotidebiosynthe

19、sisPPP in rapidlyPPP in rapidlydividing cellsdividing cellsGlucoseGlycogenCyclic esterThe Non-oxidative phase of PPPIsomerization &epimerization of Ru5PCarbon-carbon bond cleavage and formationTPPTPP转羟乙醛酶转羟乙醛酶转二羟丙酮基酶转二羟丙酮基酶Ribulose 1,5-bisphophate is regenerated alsovia this pathway in the Calvin cy

20、cle.GlycolysisTwo other ways ofdisplaying the PPPTPP is involved in the C-C cleavage and formation TPP is involved in the C-C cleavage and formation reaction catalyzed by reaction catalyzed by transketolasetransketolase: transferring: transferringtwo carbons from a ketose to an aldose. two carbons f

21、rom a ketose to an aldose. Transaldolase catalyzes a reaction in which a three-carbonunit is transferred from a ketose to an aldose without being helped by any cofactor.lD-glucose is a commonly used fuel and versatile D-glucose is a commonly used fuel and versatile precursor in almost all organisms.

22、precursor in almost all organisms.lThe study of glucose degradation has a rich The study of glucose degradation has a rich history in biochemistry (especially for history in biochemistry (especially for enzymology).enzymology).lGlucose is first converted into two three-carbon Glucose is first conver

23、ted into two three-carbon pyruvates via the ten-step glycolysis pathway pyruvates via the ten-step glycolysis pathway without directly consuming Owithout directly consuming O2 2 and with a net and with a net production of two ATP molecules by substrate-production of two ATP molecules by substrate-le

24、vel phosphorylation.level phosphorylation.lLimited amount of energy can be released by Limited amount of energy can be released by oxidizing glucose under anaerobic conditions by oxidizing glucose under anaerobic conditions by fermentation.fermentation.lThe enzymes participating glycolysis may form

25、The enzymes participating glycolysis may form multiple enzyme complexes, where substrate is multiple enzyme complexes, where substrate is channeled from one enzyme to another.channeled from one enzyme to another.lThe sugar units on glycogen is converted to The sugar units on glycogen is converted to

26、 glucose 1-phosphate via phosphorolysis, which is glucose 1-phosphate via phosphorolysis, which is catalyzed by glycogen phosphorylase.catalyzed by glycogen phosphorylase.lGlucose 6-phosphate can also be oxidized to Glucose 6-phosphate can also be oxidized to form ribose 5-phosphate and NADPH via the form ribose 5-phosphate and NADPH via the pentose phosphate pathway.pentose phosphate pathway.