1、Metabolism of CarbohydratesConcept of carbohydrate 碳水化合物，其化学本质为多羟醛或多羟碳水化合物，其化学本质为多羟醛或多羟酮类及其衍生物或多聚物。酮类及其衍生物或多聚物。Classes of carbohydrate monosacchride oligosacchridepolysacchrideglycoconjugateOHOHHHOHHOHOOHOOHHHHOHOHHOHHCH2OH glucose 已醛糖已醛糖 fructose 已酮糖已酮糖 OHOHOHOHHHOHHOHMonosacchrideOOHOHHOH2CHHOHHCH
2、2OHOOHHHOHHOHHOHHCH2OHOHHHHOHOHOHHOH2COHOHOHOHHOHHHOH galactose 已醛糖已醛糖 ribose 戊醛糖戊醛糖 OHHOHHOHOHOHOligosacchridemaltose:glucoseglucose sucrose:glucosefructoselactose:glucosegalactose能水解生成几分子单糖的糖，各单糖之能水解生成几分子单糖的糖，各单糖之间借脱水缩合的糖苷键相连。间借脱水缩合的糖苷键相连。Polysacchride能水解生成多个分子单糖的糖。能水解生成多个分子单糖的糖。starchglycogencell
3、uloseStarch:one of the chief forms in which plants store food 淀粉淀粉颗粒颗粒 glycogen :the forms of glucose stored in the animals Non-reduced Reduced cellulose：食物中含有，人体因无食物中含有，人体因无-糖苷酶而不能利糖苷酶而不能利用。有刺激肠蠕动等作用。用。有刺激肠蠕动等作用。-1,4-糖苷键糖苷键Section I1.Provide the energy-major function2.carbo-sources of other materia
4、ls in the body:amino acids,fats,cholesterol 3.Components of cells：glycoprotein、proteoglycan、glycolipid,etc.,nucleotides Digestion and Absorption of carbohydratesDigestion of CarbohydratesMonosaccharidesDo not need hydrolysis before absorptionVery little(if any)in most feedsDi-and poly-saccharidesRel
5、atively large moleculesMust be hydrolyzed prior to absorptionHydrolyzed to monosaccharidesOnly monosaccharides can be absorbedstarchMaltose+麦芽三糖麦芽三糖（40%）（25%）Dextrin+异麦芽糖异麦芽糖 （30%）（5%）glucoseSalivary Amylase-葡萄糖苷酶葡萄糖苷酶-临界糊精酶临界糊精酶 Process of digestion 肠粘膜肠粘膜上皮细上皮细胞刷状胞刷状缘缘 stomach MouthMouthSmall Inte
6、stinePancreatic AmylaseOverview Monogastric Carbohydrate DigestionLocation Enzymes Form of Dietary CHOMouth Salivary Amylase Starch Maltose Sucrose LactoseStomach (amylase from saliva)DextrinMaltoseSmall Intestine Pancreatic Amylase Maltose Brush Border Enzymes Glucose Fructose Galactose +Glucose Gl
7、ucose GlucoseLarge Intestine NoneBacterial Microflora Ferment Cellulose Carbohydrate Absorption location：duodenum and jejunum formation：monosacchride mechanism：active transportNa+-dependent glucose transporter,SGLTADP+Pi ATP G Na+K+Na+pumpIntestinal epithelial cell 肠肠腔腔 Portal VeinBrush Border细胞内膜细胞
8、内膜 Carbohydrates MonosaccharidesSmall IntestineActive TransportLiverPortal VeinDistributed to tissue through circulationG L U T(g l u c o s e transporter)G L U T 15)Outline of carbohydrate metabolism Glucose酵解途径 pyruvateAerobicanaerobicH2O及CO2 lactate糖异生途径 lactate、amino acid、glycerol glycogen肝糖原分解 糖
9、原合成磷酸戊糖途径 ribose +NADPH+HNADPH+H+starchDigestion and absorption ATPATP catabolic pathway of carbohydratesanaerobic glycolysisAerobicoxidationpentose pathwaySection IIGlycolysisThe process of glycolysis Stage I：glucose digested to pyruvate Glycolysis pathway stageII：The conversion of pyruvate to lact
10、ate*Definition：Glycolysis is the sequence of reactions that converts glucose into lactate with the concomitant production of ATP,under anaerobic conditions*two stages of glycolysis *the reaction site:cytosol The conversion of glucose to Glucose-6-phosphateATP ADPMg2+hexokinaseGlu G-6-P F-6-P F-1,6-2
11、PATP ADP ATP ADP 1,3-diphospho-glycerate3-phospho-glycerate2-phosphoglyceratepyruvateDihydroxyacetone phosphateGlyceraldehyde 3-phosphateNAD+NADH+H+ADPATPADPATPPhosphoenolpyruvate（一）（一）The conversion of one molecule of glucose two molecules of pyruvateATP neededUnreverse reaction HCCCCCCH2OHOHOHOHHH
12、OHHOHPO3H2CHOCCCCCH2HOHHOHOHHHOHOGlucose-6-phosphate G-6-PFour types of hexokinase in the mammals (typeto)Type located in the liver cells：appetency to glucose is very lowregulated by hormones The conversion of glucose-6-phosphate to fructose-6-phosphatePhosphoglucoseisomeraseGluG-6-PF-6-PF-1,6-2PATP
13、ADPATPADP1,3-diphospho-glycerate3-phospho-glycerate2-phosphoglyceratepyruvateDihydroxyacetone phosphateGlyceraldehyde 3-phosphateNAD+NADH+H+ADPATPADPATPPhosphoenolpyruvateglucose-6-phosphate(G-6-P）HCCCCCCH2OOHOHOHHHOHHOHPOOHOHfructose-6-phosphate(F-6-P）OHCH2CCCCCH2OOOHHHOHHOHP OOHOH The conversion o
14、f F-6-P to fructose-1,6-diphosphate ATP ADP Mg2+phosphofructokinase （FPK）GluG-6-PF-6-PF-1,6-2PATPADPATPADP1,3-diphospho-glycerate3-phospho-glycerate2-phosphoglyceratepyruvateDihydroxyacetone phosphateGlyceraldehyde 3-phosphateNAD+NADH+H+ADPATPADPATPPhosphoenolpyruvateATP neededunreverse (F-6-P）OHCH2
15、CCCCCH2OOOHHHOHHOHPOOHOHfructose-1,6-Diphosphate(F-1,6-2-P)O-CH2CCCCCH2OOOHHHOHHOHP OOHOHO-P OOHOH The conversion of F-1,6-2P converted to 2 molecules of triose phosphate aldolaseGluG-6-PF-6-PF-1,6-2PATPADPATPADP1,3-diphospho-glycerate3-phospho-glycerate2-phosphoglyceratepyruvateDihydroxyacetone pho
16、sphateGlyceraldehyde 3-phosphateNAD+NADH+H+ADPATPADPATPPhosphoenolpyruvatefructose-1,6-diphosphate(F-1,6-2P）CCCCCH2OOOHHHOHHOHCH2OPOOHOHPOOHOHDihydroxyacetone phosphateOHCH2COCH2OPOOHOHGlyceraldehyde 3-phosphateOHHOCCHCH2OPOOHOH The isomerization of triose phosphateTriose phosphate isomeraseGluG-6-P
17、F-6-PF-1,6-2PATPADPATPADP1,3-diphospho-glycerate3-phospho-glycerate2-phosphoglyceratepyruvateDihydroxyacetone phosphateGlyceraldehyde 3-phosphateNAD+NADH+H+ADPATPADPATPPhosphoenolpyruvateO HCH2COCH2O P OOHOHOHHOCCHCH2OPOOHOHdihydroxyacetone phosphateglyceraldehyde 3-phosphate One molecule of glucose
18、 is converted to two molecules of glyceraldehyde 3-phosphate，which consumes two ATP The following steps can be regarded as the reaction of two glyceraldehyde 3-phosphate oxygenation of glyceraldehyde 3-phosphate to 1,3-diphospho-glyceratePi、NAD+NADH+H+Glyceraldehyde3 phosphate dehydrogenaseGluG-6-PF
19、-6-PF-1,6-2PATPADPATPADP1,3-diphospho-glycerate3-phospho-glycerate2-phosphoglyceratepyruvateDihydroxyacetone phosphateGlyceraldehyde 3-phosphateNAD+NADH+H+ADPATPADPATPPhosphoenolpyruvateThe only dehydrogenation reaction in Glycolysis1,3-BPG is high-energy compoundOHHOCCHCH2OPOOHOHOHO-OCCHCH2OPOOHOH
20、PO32-Glyceraldehyde 3-phosphate1,3-diphospho-glycerate(1,3-BPG)diphosphoglycerate to 3-phosphoglycerateADP ATP Phosphoglycerate kinaseGluG-6-PF-6-PF-1,6-2PATPADPATPADP1,3-diphospho-glycerate3-phospho-glycerate2-phosphoglyceratepyruvateDihydroxyacetone phosphateGlyceraldehyde 3-phosphateNAD+NADH+H+AD
21、PATPADPATPPhosphoenolpyruvate 1st substrate-level phosphorylationHOHOOCCHCH2OPOOHOHOHO-OCCHCH2OPOOHOHOPO32-diphosphoglycerate(1,3-BPG)3-phosphoglycerate The conversion of 3-phospho-glycerate to 2-phosphoglyceratePhosphoglycerate mutaseGluG-6-PF-6-PF-1,6-2PATPADPATPADP1,3-diphospho-glycerate3-phospho
22、-glycerate2-phosphoglyceratepyruvateDihydroxyacetone phosphateGlyceraldehyde 3-phosphateNAD+NADH+H+ADPATPADPATPPhosphoenolpyruvateHOHOOCCHCH2OPOOHOHOHHO-OOCCHCH2O-POOHOH3-phospho-glycerate2-phosphoglycerate The conversion of 2-phosphoglycerate to phosphoenolpyruvateenolase(Mg2+/Mn2+)GluG-6-PF-6-PF-1
23、,6-2PATPADPATPADP1,3-diphospho-glycerate3-phospho-glycerate2-phosphoglyceratepyruvateDihydroxyacetone phosphateGlyceraldehyde 3-phosphateNAD+NADH+H+ADPATPADPATPPhosphoenolpyruvatePEP is a high energy compoundHOHHOOOCCCH2POOHOHO-HOOCCCH2P+OOHOH2-phosphoglycerate phosphoenolpyruvateH2OADP ATP K+Mg2+Py
24、ruvate kinaseGluG-6-PF-6-PF-1,6-2PATPADPATPADP1,3-diphospho-glycerate3-phospho-glycerate2-phosphoglyceratepyruvateDihydroxyacetone phosphateGlyceraldehyde 3-phosphateNAD+NADH+H+ADPATPADPATPPhosphoenolpyruvate The conversion of Phosphoenolpyruvate to pyruvate2nd substrate-level phosphorylation Phosph
25、oenolpyruvateO-HOOCCC H2P+OO HO HenolpyruvateCOO HO HC H2CCH3OCCOOHpyruvate(二二)The conversion of two molecules of pyruvate to two molecules of lactate pyruvatelactateNADH+H+may come from dehydrogenation of Glyceraldehyde 3-phosphateLactate dehydrogenase (LDH)NADH+H+NAD+COOHCHOHCH3COOHC=OCH3E1:hexoki
26、nase E2:phosphofructokinaseE3:Pyruvate kinaseNAD+lactateGluG-6-PF-6-PF-1,6-2PATP ADP ATPADP1,3-diphosphoglycerate3-phospho-glycerate2-phosphoglyceratepyruvateDihydroxyacetone phosphateGlyceraldehyde 3-phosphateNAD+NADH+H+ADP ATP ADP ATPphosphoenolpyruvateE2E1E3NADH+H+Summary of glycolysis reaction s
27、ite：cytosol Glycolysis is an anaerobic process including three unreverse reactions G G-6-P ATP ADP hexokinaseATP ADP F-6-P F-1,6-2P phosphofructokinaseADP ATP PEP pyruvatePyruvate kinase The form and numbers of energy production form：substrate-level phosphorylation Pure numbers of ATP：One molecule o
28、f glucose 22-2=2ATPOne glucose unit from glycogen 22-1=3ATP fates of lactate Used by degradationLactate cycle（gluconeogenesis）fructosehexokinaseGluG-6-PF-6-PF-1,6-2PATPADPATPADPpyruvategalactoseGalactose-1-PGlucose-1-PkinaseisomeraseMannose Mannose-6-PhexokinaseisomeraseOther hexoses can enter into
29、glycolysis二、二、regulation of glycolysisKey enzymes hexokinase phosphofructokinase Pyruvate kinaseForms allosteric regulation covalent modification （一）（一）6-phosphofructokinase-1(PFK-1)*allosteric regulation allosteric activator：F-2,6-2P;AMP;ADP;F-1,6-2P;allosteric inhibitor：citric acid;ATPATP F-1,6-2P
30、 activated by positive feed back AMP、ATP compete the allosteric site outside of the activation centerF-6-P F-1,6-2P ATP ADP PFK-1PP2BPi PKA ATP ADP Pi GlucagonATP cAMP activationF-2,6-2P +/+AMP +citric acidAMP+citric acidPFK-2（with activation）FBP-2（without activation）6-PFK-2 PFK-2（without activation
31、）FBP-2（with activation）PPFructose Bisphosphatase-2 （二）二）Pyruvate kinase1.allosteric regulation allosteric inhibitor：ATP,Alanine allosteric activator：fructose-1,6-diphosphate2.Regulation of covalent modification Pyruvate kinasePyruvate kinaseATP ATP ADP ADP Pi phosphoprotein phosphatase（without activ
32、aiton）（with activation）GlucagonPKA,CaM kinasePKA,CaM kinaseP PPKA：protein kinase ACaM：Calmodulin (三三)hexokinase or glucose kinase*Glucose-6-phosphate has feedback inhibition on hexokiase，but has no effect on glucose kinase in liver*Long-chain acyl-CoA esters has allosteric inhibition on glucose kina
33、se in liver 三、三、Physiologic role of glycolysis The effective way of energy production under anaerobic conditions2.The important energy production pathway under anaerobic conditions in some cells Cells without mitochondria：red blood cells cells with active metabolism：white blood cells,bone marrow cel
34、lsSection III Aerobic Oxidation of CarbohydrateReaction site：cytosol and mitochondriaconcept:when oxygen is enough，glucose oxidation is processing completely to produce H2O and CO2，and to release energy.The Process of Aerobic Oxidation of CarbohydratesStage 1：glycolysis pathwayStage 2：oxidative deca
35、rxylation of pyruvateStage 3：TAC cycle G（Gn）Stage 4：oxidative phosphorylationpyruvateacetyl CoA CO2 NADH+H+FADH2H2O O ATP ADP TAC cycle cytosolmitochondria（一）（一）oxidative decarboxylation of pyruvatepyruvateacetyl CoA NAD+,HSCoA CO2,NADH+H+Pyruvate Dehydrogenase complexComponents of Pyruvate Dehydrog
36、enase complex enzymeE1：Pyruvate Dehydrogenase E2：Dehydrolipoyl Transacetylase E3：Dehydrolipoyl DehydrogenaseHSCoANAD+co-enzyme TPP Lipoic acid（)HSCoA FAD,NAD+SSLCO2 CoASHNAD+NADH+H+5.NADH+H+的生成的生成1.-羟乙基羟乙基-TPP的生成的生成 2.乙酰硫辛酰乙酰硫辛酰胺的生成胺的生成 3.乙酰乙酰CoA的生成的生成4.硫辛酰胺的生成硫辛酰胺的生成 TAC、citric acid cycle、Krebs cyc
37、leTricarboxylic acid Cycle,TAC*introductionReaction site mitochondriaCoASHNADH+H+NAD+NAD+NADH+H+FADFADH2NADH+H+NAD+H2OH2OH2OCoASHCoASHH2O Citrate synthaseaconitaseaconitase Isocitrate dehydrogenase-ketoglutaratedehydrogenase complexsuccinyl-CoA synthetasesuccinyl-CoA synthetase Succinate dehydrogena
38、se Succinate dehydrogenasefumurasefumuraseMalate dehydrogenaseMalate dehydrogenaseGTPGDPATPADPAMP kinase Synthesis of citrate：un-reverse reaction O=C-COOH CH3 CH2COOH CH2 +C=O HO-C-COO-COOH SCoA CH2COOHOxaloacetate acetyl CoA citrateCitrate synthaseH2OCoA-SHUn-reverse reaction synthesis of isocitrat
39、e COO-COO-COO-CH2 CH H-C-OH-OOC-C-OH -OOC-C -OOC-C-H CH2 CH2 CH2 COO-COO-COO-Citrate cis-Aconitate isocitrate H2OH2O 1st oxidative decarboxylation to form-ketoglutarate：COO-COO-H-C-OH C=O-OOC-C-H CH2 CH2 CH2 COO-COO-isocitrate -ketoglutarateIsocitrate dehydrogenase NAD+NADH+H+CO2Mg2+Un-reverse react
40、ion 1st oxidative decarboxylation to form succinyl-CoA:COO-O=CSCoA C=O CH2 CH2 CH2 CH2 COO-COO-ketoglutarate succinyl-CoA high energy compound-ketoglutarate dehydrogenase complexNAD+CoA-SHNADH+H+CO2Un-reverse reactionsubstrate-level phosphorylation：catalysed by succinyl-CoA synthetaseO=CSCoA COO-CH2
41、 CH2 CH2 CH2 COO-COO-succinyl-CoA succinateThe only substrate-level phosphorylation in TAC to produce GTPsuccinyl-CoA synthetaseGDP+PiGTP+CoA dehydrogenation of succinate to form fumarate:CH2-COO-HC-COO-CH2-COO-OOC-C-H Succinate fumarate Succinate dehydrogenaseFADFADH2 Formation of malate：HC-COO-HO-
42、CH-COO-OOC-C-H CH2-COO-fumarate malate fumuraseH2O Formation of Oxaloacetate：HO-CH-COO-O=C-COOH CH2-COO-CH2-COO-Malate Oxaloacetate MalatedehydrogenaseNAD+NADH+H+Summary of TAC Concept of TAC：Acetyl-CoA+Oxaloacetatecitrate repeat dehydrogenation and decarboxylation Oxaloacetate.Acetyl-CoA is oxidate
43、d.the reaction is located in mitochondria Points of TAC cycle Four times of dehydrogenation，three un-reverse reaction,two times of decarboxylation，one time of substrate-level phosphorylation After TAC cycle,one molecular of acetyl-CoA forms：1 FADH2，3 NADH+H+，2 CO2，1 GTP.Total:12ATP。Key enzymes：Citra
44、te synthase -ketoglutaratedehydrogenase complex Isocitrate dehydrogenase the reaction cycle can not be reversed TCA Cycle Intermediates act as catalyzer without change of amount Oxaloacetate and other TAC cycle Intermediates can not be synthesized directly from acetyl-CoA Intermediates can not be di
45、rectly oxidated in TAC cycle to form CO2 and H2O Role of TCA Cycle Intermediates：Some of the Cycle Intermediates can be converted to other materials,for example：Oxaloacetateaspartate e-ketoglutarateGlutaminecitrateFatty acid Succinyl CoA porphyrin When sugar supply is not enough，malate、oxaloacetatep
46、yruvateacetyl-CoA TAC，the absence of oxaloacetateTAC obstacle oxaloacetateoxaloacetate decarboxyase Pyruvate CO2 malate苹果酸酶苹果酸酶 Pyruvate CO2 NAD+NADH+H+oxaloacetate oxaloacetatecitratecitrateCitratelyaseAcetyl-CoA pyruvatepyruvatePyruvatecarboxylase CO2 malatemalateMalatedehydrogenaseNADH+H+NAD+aspa
47、rtateglutamineoxaloacetic transaminase-ketoglutarateglutamineglutamine The common pathway of oxidative degradation of three major nutrients The hinge linked the metabolism of three major nutrients Providing small precursor molecules for metabolsim of other substances Procviding H+e for respiratory c
48、hainH+e enter into respiratory chain where they can be oxidation completely to produce H2O,coupled with oxidative phosphorylation to form ATP from ADPNADH+H+H2O、3ATP O H2O、2ATP FADH2 O 二、二、Aerobic Oxidation to create ATP 1mol glucoseStage I：2（3）2+4-2=6（8）Stage II：3 2=6Stage III：122=24Tptal =36（38）mo
49、l The physiological significance of Aerobic Oxidation The most major pathway to provide energy in most tissues of the human beings三、三、regulation of Aerobic Oxidation glycolysis glycolysis：hexokinase oxidative decarboxylation of pyruvate：Pyruvate Dehydrogenase complex TAC cycle：citrate synthase Pyruv
50、ate kinase 6-phosphofructokinase-1-ketoglutarate dehydrogenase complexIsocitrate dehydrogenaseKey enzymes1.Pyruvate Dehydrogenase complex allosteric regulationallosteric inhibitor：Acetyl-CoA;NADH;ATP allosteric activator：AMP;ADP;NAD+*Acetyl-CoA/HSCoA or NADH/NAD+，inhibit Regulation of covalent modif
