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Chap 4 Metabolism of Carbohydrates 目录 Substance metabolism 目录 Relationship of each metabolism External substance → internal subtance Assimilation Metab olism Micromolecule→Biomacromolecule Anabolism Endergonic reaction Exergonic reaction Energy metabolism Substance metabolism Dissimilation Biomacromolecule→Micromolecule Catabolism Internal substance → External substance 目录 Definition of carbohydrate (saccharide) Carbohydrates: Carbohydrates are polyhydroxy aldehydes or ketones, or substances that yield such compounds on hydrolysis. 目录 classes and structure of carbohydrates: Carbohydrates are classified into four types according to their hydrolysates: monosaccharide oligosaccharide polysaccharide glycoconjugate 目录 monosaccharide It’s the simplest of the carbohydrates that could not be hydrolyzed any more. glucose (aldohexose) fructose (ketohexose) O H HO H H CH2OH O H H H H OH H OH OH HO H OH OH OH OH OH O O HO H H OH H OH OH CH 2OH HOH 2C H OH H OH H OH galactose ( aldohexose ) ribose (aldopentose) O O H HO OH CH2OH H HO HO H H OH OH OH H OH H H OH H H OH H OH H OH OH OH O HOH 2C H H HO OH H OH H oligosaccharide Consist of short chains of monosaccharide units, or residues, joined by characteristic linkages called glycosidic bonds. The most abundant Are the disaccharides, with two monosaccharide units. The common disaccharides: maltose:glucose — glucose sucrose:glucose — fructose lactose:glucose — galactose 目录 polysacchride The polysaccharides are sugar polymers containing more than 20 or so monosaccharide units, and some have hundreds or thousands of units. The common polysaccharides: starch glycogen cellulose 目录 • Starch —— The most important storage polysaccharides are starch in plant cells Starch granules • Glycogen —— glycogen are stored forms of fuel in animal cells • cellulose —— the skeleton of plants ß1-4 linkage hydrogen bond microfibril Individual cellulose molecule fiber glycoconjugate the informational carbohydrate is covalently joined to a protein or a lipid to form a glycoconjugate, which is the biologically active molecule. The common glycoconjugates : glycolipid:a compound that consists of a lipid and a carbohydrate glycoprotein:have one or several oligosaccharides of varying complexity joined covalently to a protein. 目录 Part I Introduction 目录 1. The main physiological function of carbohydrate: Oxidation of fuel The main function of carbohydrates is to provide your body with energy and carbon. Source of material for anabolism e.g. Carbohydrate provides material for synthesis of amino acid, nucleotide, coenzyme, fatty acid, or other metaboli Structural elements of cells and tissues c intermediate. e.g. Carbohydrates are components of glycoprotein, proteoglycans and glycolipids. 目录 2. Digestion and absorption of carbohydrates Digestion of carbohydrates: For most humans, starch is the major source of carbohydrates in the diet which including plant starch, Animal glycogen, maltose, sucrose, lactose and glucose. Digestion site:most in the small intestine, some in the mouse 目录 Process of digestion: Starch Oral cavity Enteric cavity α-amylase in saliva α-amylase in pancreatic Maltose + maltotriose (40%) (25%) brush border of Intestinal epithelial cells α-limit dextrin + isomaltose (30%) (5%) α-limit dextrinase α-glucosidase Glucose 目录 Despite the fact that humans cannot digest cellulose (lacking an enzyme to hydrolyze the (ß 1,4) linkages), cellulose is nonetheless a very important part of the healthy human diet. This is because it forms a major part of the dietary fiber that we know is important for proper digestion. Since we cannot break cellulose down and it passes through our systems basically unchanged, it acts as what we call bulk or roughage that helps the movements of our intestines. 目录 absorption of carbohydrates absorption position : small intestine The upper Absorption Type :monosaccharide 目录 Absorption mechanism Lumen Mucosal cells of Intestinal Portal K+ ATP + Na ADP+Pi PUMP Na+ G Brush border cellular inner membrane Na+-dependent glucose transporter, SGLT 目录 3.Overview of carbohydrate metabolism Glucose are transported into cells Lumen of small intestinal SGLT Intestinal epithelial cells portal A variety of tissue cells GLUT Circulation liver This process is dependent on glucose transporter (GLUT). 目录 Extracellular Extracellular α、β-amylase intestinal(amylase、oligase) Polysaccharide and oligosaccharide monosaccharide (glucose) intracellular Phosphorylase glycogen Activation hydrolysis Transferase Debranching enzyme Branchedchain break Phosphorylase Activation hydrolysis 目录 The sources and outlet of blood glucose aerobic conditions CO2 + H2O Provide energy Carbs in food Pyruvate Digestion absorption Bread down glycogen glycolysis Blood glucose anaerobic conditions lactate Synthesis of glycogen liver (muscle) glycogen PPP Gluconeogenesis anabolism Other carbs Non-sugar substances Fat, amino acid 目录 Part II Glycolysis 目录 Glycolysis: A process in which glucose is partially broken down to two molecules of pyruvate (it is converted into lactate finally ) by cells in enzyme reactions that do not need oxygen. Glycolysis is also called anaerobic oxidation. Position of glycolysis:cytoplasm 目录 1. Glycolysis Has Two Phases: Phase I------ glycolytic pathway: The sixcarbon glucose break down into two molecules of the three-carbon pyruvate. Phase II: Pyruvate is converted to lactate. 目录 Phase I------ glycolytic pathway: The six-carbon glucose break down into two molecules of the three-carbon pyruvate 1. Phosphorylation of Glucose 目录 Hexokinase, which catalyzes the entry of free glucose into the glycolytic pathway, is a regulatory enzyme. There are four isozymes (designated I to IV). The predominant hexokinase isozyme of liver is hexokinase IV (glucokinase). Characteristic:①Low affinity to glucose; ②Regulated by hormone; Glucokinase play a critical role in the maintenance of blood glucose and metabolism of carbohydrates. 目录 2. Conversion of Glucose 6-Phosphate to Fructose 6-Phosphate 目录 3. Phosphorylation of Fructose 6Phosphate to Fructose 1,6-Bisphosphate 6-phosphfructokinase-1 目录 4. Cleavage of Fructose 1,6-Bisphosphate + Aldolase 目录 5. Interconversion of the Triose Phosphates 目录 6. Oxidation of Glyceraldehyde 3Phosphate to 1,3-Bisphosphoglycerate 目录 7. Phosphoryl Transfer from 1,3Bisphosphoglycerate to ADP The formation of ATP by phosphoryl group transfer from a substrate such as 1,3bisphosphoglycerate is referred to as a substrate-level phosphorylation 目录 8. Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate 目录 9. Dehydration of 2-Phosphoglycerate to Phosphoenolpyruvate 目录 10. Transfer of the Phosphoryl Group from Phosphoenolpyruvate to ADP COOH C O ADP P K+ Mg2+ ATP COOH C=O pyruvate kinase CH2 Phosphoenolpyruvate CH3 Pyruvate 目录 Phase II: COOH Pyruvate is converted to lactate. NADH + H+ NAD+ COOH CHOH C=O Lactate dehydrogenase (LDH) CH3 CH3 Pyruvat Lactate e NADH+H+ needed in this reaction is provided by Oxidation of Glyceraldehyde 3Phosphate in step 6 of glycolytic pathway. 目录 Glu E1 E2 F-1, 6-2P ATP ADP G-6-P F-6-P ATP ADP Dihydroxyacetone phosphate E1:Hexokinase E2: Phosphofructokinase-1 E3:Pyruvate kinase Glyceraldehyde 3phosphate NAD+ NADH+H+ 2×1,3-Bisphosphoglycerate ADP ATP 2× 3-Phosphoglycerate lactate NAD+ Glycolysis 2× 2-Phosphoglycerate NADH+H+ ATP ADP 2×pyruvate 2× Phosphoenolpyruvate E3 目录 Summary of glycolysis Position of glycolysis:cytoplasm Glycolysis is an anaerobic process through which ATP is synthesized . There are three irreversible steps in the process. ATP ADP G G-6-P Hexokinase ATP F-6-P Phosphofructokinase-1 ADP PEP ADP F-1,6-2P ATP Pyruvate kinase Pyruvate 目录 Method and Quantity of energy-producing: Method: substrate-level Phosphorylation Quantity of ATP:From G 2×2-2= 2ATP From Gn 2×2-1= 3ATP Fates of lactate: Lactate is released into blood and metabolized in liver Decomposition Cori cycle(glyconeogenesis) 目录 Many hexose besides glucose meet their catabolic fate in glycolysis, after being transformed into hexosephosphate Mannose hexokinase Mannose 6-phosphate Glu galactose galactokinase UDP-galactose ATP ADP G-6-P mutase Glucose 1-phosphate F-6-P ATP Fructose ADP F-1,6-2P Pyruvae 目录 2. Regulation of Glycolysis: 3 key enzymes ① Hexokinase Key Enzymes ② Phosphofructokinase-1 ③ Pyruvate kinase ① allosteric regulation Method of regulatio n ② covalent modification 目录 1.Phosphofructokinase-1 (PFK-1) is the most important enzyme to regulate the yield of glycolysis Allosteric regulation allosteric activator:AMP; ADP; F-1,6-2P; F-2,6-2P allosteric inhibitor:citrate; ATP(High level) 目录 ATP regulate the acitivity of Phosphofructokinase-1 (PFK-1) ATP binding site Regulation substrate-binding site in active center (low level) allosteric regulation site beside active center(high level) activation inhibition 目录 Fructose 2,6-bisphosphate regulate the activity of Phosphofructokinase-1 (PFK-1) Fructose 2,6-bisphosphate is the strongest allosteric activator of Phosphofructokinase-1 When fructose 2,6-bisphosphate binds to its allosteric site on PFK-1, it increases that enzyme’s affinity for its substrate, fructose 6-phosphate, and reduces its affinity for the allosteric inhibitors ATP and citrate. 目录 AMP Citrate Glucagon – + PFK-2 FBP-2 (active) ATP cAMP (inactive) 6-PFK-2 ATP F-6-P Activate Phosphoprotein phosphatase PKA F-2,6-2P FBPase-2 ATP + ADP P PFK-2 FBP-2 (inactive) (active) ADP –/+ PFK-1 + + F-1,6-2P AMP Pi P Pi + – Citrate PKA:protein kinase A Glucogen Fat Glucose Fatty acie+ Glycerine Ⅱ Protein Acetyl-CoA Oxaloacetate Malate Ⅲ Amino acid Citrate α-Ketoglutarate Succinate CO2 Succinyl-CoA 2H+ Oxidative phosphorylation ADP+Pi ATP 目录 2. Pyruvate kinase is the second regulation point of glycolysis Allosteric regulation allosteric activator:F-1,6-2P allosteric inhibitor:Alanine; ATP. 目录 Covalent modification regulation Pi phosphoprotein phosphatase Pyruvate kinase (active) Pyruvate P kinase (inactive) ATP Glucagon ADP PKA, CaM kinase PKA:protein kinase A CaM: calmodulin 目录 3. Hexokinase is regulated by feedback suppression Except for liver glucokinase, hexokinase is suppressed by feedback of glucose 6-phosphate. Long-chain fatty acyl CoA is a allosteric inhibitor of glucokinase. Insulin promote the synthesis of glucokinase throuth inducing it’s transcription. 目录 3. The main physiological function of glycolysis: provide energy quickly under anaerobic conditions Glycolysis is an effective way to get energy under anaerobic conditions. The glycolytic breakdown of glucose is the sole source of metabolic energy in some mammalian tissues and cell types. ① Cells without mitochondria:erythrocytes ② Metabolic active cells:leucocyte、myeloid cell 目录 Part III Aerobic Oxidation of Carbohydrate 目录 Definition The aerobic oxidation of carbohydrates is referred to glucose is oxidized to H2O and CO2 under aerobic conditions. It’s the main energy supply mode. Glycolysis (cytoplasm) oxidative phosphorylation (mitochondria) Position:cytoplasm and mitochondria 目录 1. There are four phases in the process of aerobic oxidation of carbohydrates G(Gn) Phase I:Glytolytic pathway cytoplasma Phase II:Oxidative decarboxylation of pyruvate Acetyl-CoA Phase III:TAC cycle mitochondria Phase IV: Oxidative phosphorylation [O] H2O ATP ADP Pyrutate NADH+H+ FADH2 Citrate TAC CO2 目录 1. Glucose break down into two molecules of the three-carbon pyruvate in glycolytic pathway 2. Pyruvate is oxidized to Acetyl-CoA and CO2 in mitochondria Overall reaction : NAD+ , HSCoA CO2 , NADH + H+ Acetyl-CoA Pyruvate pyruvate dehydrogenase complex 目录 HSCoA The composition of pyruvate dehydrogenase complex NAD+ enzymes E1:pyruvate dehydrogenase Coenzymes TPP S E2:dihydrolipoyl transacetylase lipoate(L HSCoA ) S E3:dihydrolipoyl dehydrogenase FAD, NAD+ 目录 Oxidative decarboxylation of pyruvate to acetyl-CoA by the PDH complex. 1. Pyruvate reacts with the bound thiamine pyrophosphate (TPP) of pyruvate dehydrogenase (E1), undergoing decarboxylation to the Hydroxyethyl derivative. 2. Form the acetyl thioester-E2 of the reduced lipoyl group. 3. The -SH group of CoA replaces the -SH group of E2 to yield acetyl CoA and the fully reduced (dithiol) form of the lipoyl group. 4. Dihydrolipoyl dehydrogenase (E3) promotes transfer of two hydrogen atoms from the reduced lipoyl groups of E2 to the FAD prosthetic group of E3, restoring the oxidized form of the lipoyllysyl group of E2. 5. The reduced FADH2 of E3 transfers a hydride ion to NAD+ forming NADH. 目录 1.Generation of -hydroxyethyl-TPP CO2 2.Generation of Acyl lipoyllysine NADH+H+ 5. Generation of NADH+H+ NAD+ CoASH 3.Generatin of AcetylCoA 4. Generation of lipoyllysine 2. TCA is a circulation response system based on the formation of citric acid as starting material overview Tricarboxylic Acid Cycle (TAC) is also named citric acid cycle,because the first intermediate product is citric acid containing three carboxylor, or the Krebs cycle (after its discoverer, Hans Krebs). Position of reaction :mitochondria 目录 1. The Citric Acid Cycle Has Eight Steps 1. The condensation of acetyl-CoA with oxaloacetate to form citrate. 2. Formation of Isocitrate via cis-Aconitate. 3. Oxidation of Isocitrate to α-Ketoglutarate and CO2. 4. Oxidation of α-Ketoglutarate to Succinyl-CoA and CO2. 5. Conversion of Succinyl-CoA to Succinate. 6. Oxidation of Succinate to Fumarate. 7. Hydration of Fumarate to Malate. 8. Oxidation of Malate to Oxaloacetate 目录 H2O H2O ② ① NADH+H+ H2O CoASH ② NAD+ ①citrate synthase ②aconitase ③isocitrate dehydrogenase ④α-ketoglutarate dehydrogenase complex + NAD GTP GDP ⑤succinyl-CoA synthetase nucleoside diphosphate kinase ⑥succinate dehydrogenase NADH+H+ ⑦ ⑦fumarase ③ ⑧malate dehydrogenase H2O FADH + ⑧ ADP ⑥ NAD 2 ATP FAD GDP+Pi GTP NADH+H+ ④ ⑤ CoASH CO2 CoASH CO2 ⑴ Formation of Citrate: Inreversible reaction 目录 ⑵ Formation of Isocitrate 目录 ⑶ Oxidation of Isocitrate to α-Ketoglutarate : Mg2+ Inreversible reaction 目录 ⑷Oxidation of α-Ketoglutarate to Succinyl-CoA Inreversible reaction 目录 ⑸substrate-level phosphorylation:Conversion of Succinyl-CoA to Succinate The only substrate-level phosphorylation reaction which produced GTP in TAC 目录 ⑹ Oxidation of Succinate to Fumarate: 目录 ⑺Hydration of Fumarate to Malate: H2O 目录 ⑻Oxidation of Malate to Oxaloacetate: 目录 Summary: Definition of TAC : Acetyl-CoA entered the cycle by combining with oxaloacetate to form citrate containing three carboxyls. Two carbon atoms emerged from the cycle as CO2 from the oxidation of isocitrate and α-ketoglutarate. The energy released by these oxidations was conserved in the reduction of three NAD+ and one FAD and the production of one ATP or GTP. At the end of the cycle a molecule of oxaloacetate was regenerated. Position of TAC reaction : mitochondria 目录 Four dehydrogenation One substrate level osphorylation TAC Three key enzymes One substrate level prosphorylation、 Two decarboxylation、 Three key enzymes、 Four dehydrogenation Two decarboxylation 目录 Highlight of TAC: Following a cycle : • Consumption: one Acetyl-CoA; • Undergo: four dehydrogenation,two decarboxylation, one substrate level prosphorylation; • Generation: one FADH2,three NADH+H+,two CO2, one GTP; • Key enzyme:citrate synthase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase complex. The whole cycle reaction is irreversible. 目录 intermediate product of TAC: The intermediate products of TAC performed as a catalyst without change of it’s quantity. Oxaloacetate or other intermediate products can neither be synthesized directly from Acetyl-CoA, nor be oxidized directly to CO2 and H2O in TAC. 目录 Apparently, Oxaloacetate which does not be consumed in TAC could be used in recycling. In fact: Ⅰ. Various metabolic pathways and their regulation in organism are linked and interacted each other. Some intermediate products of TAC could integrate metabolism of carbohydrate and other material by converted into other substances. e.g. Oxaloacetate α-ketoglutarate citrate Succinyl-CoA aspartate glumatic acid fatty acid porphyrin 目录 Ⅱ. When the carbohydrate supply is insufficient, it may cause circulatory disturbance of TAC. So Acetyl-CoA could by generated by pyruvate which is formed through the decarboxylization of malate or Oxaloacetate. NAD+ NADH + H+ CO2 Malate Pyruvate malic enzyme CO2 Oxaloacetate Pyruvate oxaloacetic decarboxylase Oxaloacetate must be replenished continuously 目录 The source of oxaloacetate: Citrate Acetyl-CoA CO2 Pyruvate pyruvate carboxylase Oxaloacetate Citrate lyase malate dehydrogenase Malate NADH+H+ Glu GOT NAD+ α-ketoglutarate Aspartate 目录 3. Aerobic oxidation of carbohydrate is the main method to get ATP of organism. In oxidative phosphorylation, passage of two electrons from NADH to O2 drives the formation of about 2.5 ATP, and passage of two electrons from FADH2 to O2 yields about 1.5 ATP. NADH+H+ FADH2 [O] H2O、2.5ATP [O] H2O、1.5ATP 目录 Phase I (Cytoplasma) Phase II (Mito matrix) Phase III (Mito matrix) 目录 Aerobic oxidation of carbohydrate is the main method to get ATP of organism. The generation of energy is not only efficient but also gradually in this way. The energy of oxidations in the cycle is efficiently conserved by the formation of ATP. 目录 1. TCA cycle has important physiological significance in the metabolism of three major nutrients TCA cycle is the last metabolic pathway of three nutrients to provide reducing equivalents for the generation of ATP in oxidative phosphorylation through four dehydrogenations. 2. TCA cycle is a key point to communicate the metabolism of protein, carbohydrate and fat. 目录 Glucogen Fat Glucose Fatty acie+ Glycerine Ⅱ Protein Acetyl-CoA Oxaloacetate Malate Ⅲ Amino acid Citrate α-Ketoglutarate Succinate CO2 Succinyl-CoA 2H+ Oxidative phosphorylation ADP+Pi ATP 目录 4. The regulation of aerobic oxidation of carbohydrate is dependent on the requirement of energy. Hexokinase ① Glycolytic pathway: pyruvate kinase Phosphofructokinase-1 Key Enzyme ② oxidative Pyruvate dehydrogenase complex decarboxylation of pyruvate: citrate synthase ③ TCA cycle: α-ketoglutarate dehydrogenase complex isocitrate dehydrogenase 目录 The regulation of Pyruvate dehydrogenase complex allosteric regulation allosteric inhibitor:Acetyl-CoA;NADH;ATP allosteric activator:AMP;ADP;NAD+ this enzyme activity is turned off when ample fuel is available in the form of fatty acids and acetyl-CoA and when the cell’s [ATP]/[ADP] and [NADH]/[NAD+] ratios are high. 目录 Covalent modification glucagon 目录 TCA cycle is regulated by substrate, products and the activity of key enzymes. Three factors govern the rate of flux through the cycle: substrate availability, inhibition by accumulating products, and allosteric feedback inhibition of the enzymes that catalyze early steps in the cycle. 目录 1.There are three key enzymes in TCA cycle: citrate synthase, Isocitrate dehydrogenase α-ketoglutarate dehydrogenase 目录 The regulation of TAC Acetyl-CoA – ATP Citrate NADH Succiny-CoA + ADP ① Effect of ATP、ADP citrate Oxaloacetate synthase ② inhibition by accumulating products Isocitrate Malate ③allosteric feedback FADH2 inhibition of the enzymes that catalyze early steps in the cycle. ④ others,e.g. Ca2+ activate enzymes Citrate NADH isocitrate – ATP dehydrogenase + ADP Ca2+ α--Ketoglutarate α-ketoglutarate dehydrogenase Ca2+ + complex Succiny-CoA – Succiny-CoA NADH GTP ATP 目录 2.The rates of TCA cycle and the other reactions of its upstream or downstream are integrated. Under normal conditions, the rate of glycolysis is matched to the rate of the citric acid cycle not only through its inhibition by high levels of ATP and NADH, which are common to both the glycolytic and respiratory stages of glucose oxidation, but also by the concentration of citrate which play a allosteric inhibition to PFK-1. The rate of oxidative phosphorylation play an important role in the progress of TCA cycle. 目录 Because the activity of many enzymes in the progress of oxidative phosphorylation is regulated by the rates of ATP/ADP or ATP/AMP in cells. 2ADP adenylate kinase ATP+AMP In vivo ATP concentration is 50 times of AMP. After above reaction, the change of ATP/AMP are much bigger than the change of ATP,it played an effective regulation by signal amplification 目录 5. The inhibiting effect of oxygen on the process of fermentation Definition Pasteur effect: The inhibiting effect of oxygen on the process of fermentation. Mechanism Under aerobic conditions, NADH+H+ and pyruvate enter into the mitochondria, then enters the citric acid cycle, where it is completely oxidized. Under anaerobic conditions, pyruvate is reduced to lactate, accepting electrons from NADH and thereby regenerating the NAD+ necessary for glycolysis to continue. 目录 Part IV Other Metabolism Pathways of Glucose 目录 1.Pentose phosphate pathway produces pentose phosphates and NADPH+H+ Definition Pentose phosphate pathway is the progress of glucose produces pentose phosphates and NADPH+H+, then the pentose phosphates is converted into Glyceraldehyde 3-phosphate and fructose 6-phosphate. 目录 1. The progress of pentose phosphate pathway has two phases: Position:Cytosol The reaction has two phases: Phase I: The Oxidative Phase Produces Pentose Phosphates, NADPH+H+ and CO2 Phase II:The Nonoxidative Phase Including a series of group transfer. 目录 1.glucose 6-phosphate undergoes oxidation and to form the pentose phosphates and NADPH H C OH glucose 6-phosphate dehydrogenase H C OH NADP+ HO C H H C OH H C CH2O O H C OH HO C H H C OH H C NADPH+H+ ⑴ P CH2O glucose 6-phosphate CO2 NADPH+H+ ⑵ H 2O O P H C OH H HO C H H C OH H C OH P 6-Phosphoglucono-lactone 6-Phosphogluconate CH2O CH2OH 6-phosphogluconate dehydrogenase NADP+ CO COO— C=O C=O C O H C OH H C OH CH2O P Ribulose 5-phosphate Ribose 5-phosphate 目录 NADP+ NADPH+H+ NADP+ NADPH+H+ G-6-P CO2 Ribose 5-phosphate The glucose 6-phosphate dehydrogenase which catalyze the first step is the key enzyme of the pathway. H+ produced in two dehydrogenations were accepted by NADP+ to generate NADPH + H+ . ribose phosphate generated in reaction is a very important intermediated product. 目录 2.Enter the glycolysis by the group transfer reaction The significance of phase II is the transformation of ribose to fructose 6-phospherate and Glyceraldehyde 3-phosphate by a series of group transfer reaction, then enter the glycolysis. So, pentose phosphate pathway is also named pentose phosphate shunt. 目录 Ribulose 5-phosphate (C5) Xylulose 5phosphate C5 Glyceraldehyde 3-phosphate C3 Ribose 5-phosphate C5 ×3 Xylulose 5-phosphate C5 Sedoheptulose 7-phosphate Glyceraldehyde 3-phosphate C7 C3 Erythrose 4-phosphate Fructose 6-phosphate C4 C6 Fructose 6-phosphate C6 目录 glucose 6-phosphate(C6)×3 pentose phosphate pathway 3NADP+ 3NADP+3H+ glucose 6-phosphate dehydrogenase 6-Phosphoglucono-lactone(C6)×3 Phase I 6-Phosphogluconate(C6)×3 3NADP+ 3NADP+3H+ 6-phosphogluconate dehydrogenase CO2 Ribulose 5-phosphate(C5) ×3 Xylulose 5-phosphate C5c Glyceraldehyde 3-phosphate C3 Ribose 5-phosphate C5 Xylulose 5-phosphate C5c Sedoheptulose 7-phosphate C7 Glyceraldehyde 3-phosphate C3 Erythrose 4-phosphate C4 Fructose 6-phosphate C6 Phase II Fructose 6-phosphate C6 目录 reaction formula: 3×glucose 6-phosphate + 6 NADP+ 2×Fructose 6-phosphate + Glyceraldehyde 3-phosphate + 6NADPH+H+ + 3CO2 目录 Characteristic of pentose phosphate pathway: Hydrogen receptor of dehydrogenation is NADP+ , to generate NADPH+H+。 Transaldolase and transketolase catalyze the interconversion of three-, four-, five-, six-, and seven-carbon sugars, with the reversible conversion of six pentose phosphates to five hexose phosphates. The reaction provides specialized intermediated product: ribose 5phosphate. One CO2 and two NADPH+H+ were generated by one G-6-P through one decarboxylation and two dehydrogenation in a cycle. 目录 2. The pentose phospherate pathway is regulated mainly by the ratio of NADPH/NADP+ Glucose-6-phosphate dehydrogenase is the key enzyme of the pentose phosphate pathway, the activity of this enzyme decide the flow of glucose-6phosphate which enter the pathway. The G-6-P-D is inhibited by a high ratio of NADPH/NADP+ and increased consumption of NADPH . Therefore, the flow of pentose phospherate pathway meets the needs of the cells for NADPH. 目录 3. the significance of pentose phospherate is the generation of NADPH and ribose 5-phosphate 1.Provide ribose for biosynthesis of nucleotides. 2.Provide NADPH as hydrogen donor to participate in various metabolic reactions (1)NADPH is the hydrogen donor in various anabolic; (2)NADPH participate the hydroxylation in vivo. (3)NADPH could keep the regeneration of reduced glutathione (GSH). 目录 oxidized glutathione Reduced glutathione A AH2 2G-SH G-S-S-G NADP+ NADPH+H+ Reduced glutathione is an important antioxidant which protect protein or enzyme with –SH group from the damage of oxidizing agents and peroxide in vivo. Reduced glutathione maintains the integrity of erythrocytes membrane. 目录 Favism: some people are Glucose 6-Phosphate Dehydrogenase (G6PD) deficient. their erythrocytes will lyse after ingestion of the beans (containing divicine or other oxidizing agents), releasing free hemoglobin into the blood (acute hemolytic anemia). G6PD deficiency is a X-linked recessive genetic disease. X-linked diseases usually occur in males. Males have only one X chromosome. A single recessive gene on that X chromosome will cause the disease. The geographic distribution of G6PD deficiency is instructive. It is common in the South than in the northern population 目录 Part V Glycogenesis and Glycogenolysis 目录 Structure of glycogen Nonreducing ends shape:branched polymer MW:1,000,000~ 10,000,000 Reducing end:one Nonreducing ends:poly Reducing end 目录 Distribution of glycogen Hepatic glycogen: the glycogen content of the liver is up to 8% of the fresh weight. Muscle glycogen: the glycogen concentration in muscle is 1%-2%. Back 目录 1. Most anabolism of glycogen occurred in liver and muscle. Definition: The synthesis progress of glycogen from monosaccharide is named glycogenesis. Monosaccharide: Glucose (main), fructose, galactose … Position: Cytoplasma of liver, muscle … 目录 Glucose is converted to glucose 6-phosphate CH2OH O H H OH H O H H OH OH H ADP Mg2+ H HO ATP CH2OPO3H2 OH glucose Glucose + ATP H H Glucokinase HO OH H OH glucose-6-phosphate glucose-6-phosphate+ADP Glucose-6-phosphate is isomerized to glucose-1-phosphate OH O P O CH2 OH OH HO CH2 O O OH OH OH phosphoglucomutase OH OH glucose-6-phosphate Glucose-6-phosphate OH O P OH O HO glucose-1-phosphate Glucose-1-phosphate The generation of UDP-glucose CH2OH UDPG pyrophosphorylase O H H OH H O H O HO UTP P OH OH H OH glucose-1-phosphate CH2OH O H H OH H2O 2Pi UTP+ G-1-P H H O HO PPi O H O P O P O ÄòÜÕ urdine OH HO OH UDPG (uridine diposphate glucose) UDPG+ PPi The glucose in UDPG is attached to glycogen primer CH 2OH O H H OH H O H H H OH urdine P P ÄòÜÕ HO HO H CH2OH CH2OH OH H O H OH H H H O R O UDPG OH H OH H H Gn (glycogen primer) Glycogen synthase UDP Gn+ (glycogen) O H H OH H CH2OH CH2OH CH 2OH O H H OH H H H OH OH H H H OH H H O O O HO O H H OH R The branching enzyme catalyze the formation of new branches on glycogen 12~18G Glycogen synthase Glycogen primer Branching enzyme Rate-limiting enzyme 目录 Scheme of the synthesis of glycogen glucose ATP ADP G-1-P G-6-P UTP UDPG PPi Glycogen primer Glycogen UDP (1→4 glucose unit) Energy consumption need primer nonreducing end Branching enzyme Glycogen (1→4 and 1→6 glucose unit) Back 目录 2. The production of glycogen degradation: glucose could replenish the blood glucose Glycogen-degrading The progress that glycogen is degraded to glucose. Position: Liver Production: Glucose 目录 Glycogen is phosphorolytic cleavaged to G-1-P 糖原 Gn H3PO4 PHOSPHORYLASE Rate-limiting enzyme 糖 原 Gn-1 HO CH2 O OH OH OH O P OH HO glucose-1-phosphate O Gn+ H3PO4 G-1-P + Gn-1 Nonreducing end phosphorylase Glucose-1-phospherate Pi Pi G-1-P The function of debranching enzyme Debranching enzyme Debranching enzyme has two activities: Debranching enzyme G α-1,4- transglycosylase α-1,6- glycosidase 目录 G-1-P is converted to G-6-P OH O P O CH2 OH HO CH2 O OH OH OH O P OH HO glucose-1-phosphate G-1-P O OH glycophosphomutase O OH OH OH glucose-6-phosphate G-6-P G-6-P is hydrolyzed to Glucose H2O CH2OPO3H2 H3PO4 O H H OH H H HO CH2OH OH H H Glucose -6 - phosphatase HO OH (liver) H O H H OH OH H OH glucose glucose-6-phosphate This enzyme is deficient in brain and muscle G-6-P+ H2O Glucose + H3PO4 Glycogen Gn+1 Pi phosphorylase Scheme of the glycogendegradation Gn G-1-P glucophosphomutase Catabiosis of carbohydrate G-6-P Glucose-6-phosphatase H2O Pi Glucose 目录 The synthesis and degradation of glycogen Gn+1 UDP Gn Pi Glycogen synthase Gn UDPG PPi phosphorylase UDPG pyrophosphorylase UTP G-1-P glucophosphomutase Glucose-6-phosphatase(liver) G-6-P G Hexokinase (glucokinase) 目录 Comparison of liver glycogen and muscle glycogen liver glycogen Muscle glycogen Storage 90-100g ≤5% 200-500g 1-2% Raw material cleavage product Monosaccharide/nocarbohydrate material Glucose Glucose function To maintain relatively stable of blood glucose consumption 12-18h after meal lactate To meet the energy requirement of muscles in strenuous exercise After heavy exercise 目录 3. Glycogen synthesis and glycogen 三.糖原合成与分解受到彼此相反的调节 degradation are regulated by each other Glycogen synthase Key enzyme of glycogen degradation Key enzyme of glycogen degradation Key enzyme of glycogen synthesis active Glycogen synthase inactive Glycogen synthase Phosphorylase P phosphorylase phosphorylase inactive phosphorylase P P active 目录 Hormone regulate the metabolism by cAMP-protein kinase Hormone Receptor Cell membrane G Protein cyclase ATP cAMP+PPi R c c R cAMP Protein kinase(active) Protein kinase (inactive) ATP Unphosphorylated Protein kinase covalent modification + ADP Phosphorylated Protein kinase Phosphorylation of integral protein Change the process of physiology in cells Cell membrane 目录 Hormone regulate the synthesis and degradation of liver glycogen Adrenalin/ Glucagon Adrenalin/ Glucagon 1、adenylcyclase 1 (inactive) adenylcyclase(active) 2、ATP 2 cAMP R、cAMP 3、protein kinase Signifiance: because the covalent modification of enzyme is a enzymatic reaction, a little signal (hormone) could make a large number of enzymes to be modified through accelerating this enzymatic reaction, then the signal is amplified. Such regulation is quickly and efficiently (inactive) 102 3 Protein kianse(active) ATP ADP 4 4、phosphorylase kinase(inactive) Phosphorylase kinase (active) ATP ADP 104 5 106 5、phosphorylase b (inactive) Phosphorylase a(active) 6 108 6、glycogen G-1-P blood glucose Glucose G-6-P 目录 目录 Glucagon, adrenalin adenylcyclase + Phosphorylase b kinase adenylcyclase ATP + cAMP Protein kinase + Glucagon and adrenalin regulate the synthesis and degradation of glycogen + Protein kinase Phosphorylase b kinase Glycogen synthase + Glycogen syntha Phosphorylase b + Cascade amplification effect Phosphorylase a Decrease the synthesis of glycogen Enhance the degradation of glycogen 返回 目录 The regulation of synthesis and degradation of liver glycogen allosteric regulation When the blood glucose increase G is an allosteric effector phosphorylase (a) The allosteric enzyme is susceptible to be inactive through dephosphorylation catalyzed by phosphoprotein phosphatase. Meanwhile, the glycogen synthase is activated through dephosphorylation catalyzed by phosphoprotein phosphatase. Result:G ,the synthesis of glycogen,the degradation of glycogen 目录 The synthesis and degradation of muscle glycogen Synthesis: same to liver glycogen (without three-carbons pathway) Degradation: different to liver glycogen, (without G6PE) glycogenG-6-P glycolytic pathway Regulation:adrenalin (mainly) AMP: allosteric activate phosphorylase-b ATP and G-6-P:inhibit phosphorylase-b G-6-P: allosteric activate glycogen synthase 目录 Summary of regulation: There are two forms (active or inactive) of all key enzymes, the two kinds of forms could change in each other by phosphorylation and dephosphorylation. Bidirectional regulation:synthase and lytic enzyme were regulated separately. e.g. enhance the synthesis and decrease the degradation. Duel regulation:allosteric regulation and covalent modificational regulation. There are cascade effect on the regulation of kcy enzyme. Difference of regulation on the liver and muscle glycogen: e.g. glucagon degrade the liver glycogen, adrenalin degrade the muscle glycogen. 目录 3. deficiencies of glycogen degrading enzymes lead to glycogen storage disease glycogen storage diseases is an inherited metabolism disease. Deficiencies of glycogendegrading enzymes usually lead to accumulation of glycogen in the liver or other organs. 目录 Glycogen storage diseases Type Enzyme deficiency Organ affected Structure of glycogen Ⅰ G-6-P Liver, kidney normal Ⅱ α1→4 or 1→6 glucosidase All organs normal Ⅲ Debranching enzyme Muscle, liver More branch, short peripheral carbs chain Ⅳ Branching enzyme All organs Less branch,long peripheral carbs chain Ⅴ Muscle phosphorylase muscle normal Ⅵ Liver phosphorylase Liver normal Ⅶ phosphofructokinase Muscle, erythrocyte normal Ⅷ Phosphorylase kinase Liver normal 目录 Part VI Gluconeogenesis 目录 Definition: Gluconeogenesis is the synthesis progress of glucose or glucogen from non-carbohydrate sources. Position: Cytoplasma and mitochondria of liver , kidney cells. Substrance: Pyruvate, lactate, glycerine, glycogenic amino acid. 目录 1. Gluconeogenic pathway is not a reversible reaction of glycolytic pathway completely gluconeogenic pathway is the synthesis progress of glucose from pyruvate. Progress: Most reactions of gluconeogenic pathway and glycolytic pathway are shared and reversible. Three irreversible reactions catalyzed by three key enzymes in glycolysis must by bypassed in gluconeogenesis. 目录 1. Pyruvate is converted to PEP by pyruvate carboxylation bypass ATP Pyruvate CO2 ADP+Pi GTP GDP oxalacetate ① PEP ② CO2 ① pyruvate carboxylase, coenzyme is biotin (in mitochondria). ② PEP-carboxykinase ( mitochondrion, cytoplasma) 目录 目录 Oxaloacetate export to the cytosol from mitochondria Out Oxaloacetate Oxaloacetate Malate mitochondria Malate oxalozcetate In mitochondria Aspartate Aapartate oxaloacetate 目录 PEP cytoplasma GDP + CO2 PEP-carboxykinase GTP oxaloacetate Aspartate Aspartate Malate Malate NAD+ α-ketoglutarate NADH + H+ glutamate oxaloacetate ADP + Pi mitocondria pyruvic ATP + CO2 carboxylase Pyruvate Pyruvate 目录 The resource of NADH+H+ in glyconeogenesis: The generation of glyceraldehyde-3-phosphate from 1,3-bisphosphoglycerate need NADH+H+ in glyconeogenesis. NADH+H+ is provide from latate when the latate is the resource of glyconeogenesis. LDH Latate NAD+ pyruvate NADH+H+ 目录 If amino amid is the resource of glyconeogenesis, NADH+H+ come from mitochondria where NADH+H+ are derived from β- oxadation of fatty acid or TAC. The transport of NADH+H+ dependent on the conversion of oxaloacetate and malate. oxaloac etate Malate NADH+H+ NAD+ mitochondria Malate oxaloac etate NAD+ NADH+H+ cytoplasma 目录 2. Conversion of Fructose 1,6-Bisphosphate to Fructose 6-Phosphate Pi Fructose 1,6Bisphosphate Fructose 6Phosphate fructose 1,6bisphosphatase (FBPase-1) 3. Conversion of Glucose 6-Phosphate to Glucose Pi Glucose 6-Phosphate Glucose glucose 6-phosphatase 目录 A set of forward and reverse reactions catalyzed by different enzymes are called substrate cycle. If the two kinds of enzyme activity is equal, the results of the cycle are that ATP energy is depleted, heat is produced and no net substrate-to-product conversion is achieved, so it is also called futile cycle. The two-enzyme cycle thus provides a means of controlling the direction of net metabolite flow. 目录 glucose 6-phosphatase Pi Glucose 6-Phosphate ADP Glucose hexokinase ATP FBPase-1 Pi Fructose 1,6-Bisphosphate ADP ATP PFK-1 ADP+Pi pyruvic carboxylase CO2+ATP Fructose 6-Phosphate GTP PEP-carboxykinase oxaloacetate Pyruvate ADP PEP Pyruvate kinase GDP+Pi +CO2 ATP 目录 The non-carbs substances enter the gluconeogenesis The substances of gluconeogenesis is converted to the intermediate products of carbohydrates metabolism. -NH2 Glucogenic amino acid α-oxoacid Glycerine lactate αphosphoglycerol 2H Phospho dihydroxyacetone Pyruvate Above intermediate products enter the gluconeogenesis pathway and generate to glucose or glycogen. 目录 Question about TAC The intermediate products of TAC performed as a catalyst without change of it’s quantity. Oxaloacetate or other intermediate products can neither be synthesized directly from Acetyl-CoA, nor be oxidized directly to CO2 and H2O in TAC. 目录 2. Glycolysis and Gluconeogenesis Are Regulated Reciprocally through two substrate cycle. Glycolysis and gluconeogenesis are the two metabolic pathways in opposite direction. If the gluconeogenesis from pyruvate is carried out effectively, the glycosis must be inhibited. And vice versa. This coordination is dependent on the regulation of the two substrate cycle in pathway. 目录 1. The first substrate cycle: between fructose-6-phosphate and Fructose 1,6-bisphosphate Pi Frustose-6phospherate fructose 2,6bisphosphate ATP PFK-1 FBPase-1 AMP ADP Fructose 1,6bisphosphate 目录 2. The second substrate cycle: between PEP and pyruvate PEP Fructose 1,6bisphosphate ADP Pyruvate kinase oxaloacetate alanine ATP Pyruvate Acetyl-CoA 目录 3. The physiological significance of gluconeogenesis is to maintain the stable of blood glucose. 1. The main function of gluconeogenesis: maintain the stable of blood glucose The maintenance of stable blood glucose is dependent on the gluconeogenesis from amino acid, glycerine when fasting or starvation. Under normal conditions, brain utilized energy derived from glucose because brain cells could not take energy from fatty acid; erythrocytes get the energy through glycolysis totally in the absence of mitochondria; and, bone marrow, nerves tissure are used to take glycolysis because of their active metabolism. Above mentioned glucose are generated through the gluconeogenesis. 目录 The substrate of gluconeogenesis are lactate, amino acid and glycerine. Lactate come from the muscle glycogenolysis related with exercise intensity. Amino acid and glycerine are the substrate of gluconeogenesis when in hungry. 目录 2. Gluconeogenesis is an important pathway to replenish and restore the storage of liver glycogen C3 pathway: After meal, most glucose is broken down to lactate or pyruvate which contain three carbons outside the liver cells, then these C3 substrates enter the liver cells and generate to glucogen by gluconeogenesis. 目录 3. The enhance of renal gluconeogenesis is helpful to the maintenance of acid-base balance Under long-term fasting and starve conditins, the renal gluconeogenesis is enhanced which is helpful to the maintenance of acid-base balance. The reason of this change maybe the metabolic acidosis: pH↓→ PEP-carboxykinase↑→Gluconeogenesis↑ After α–ketoglutarate is consumed in glycolysis, the deamination of glutamine and glutamic acid will be enhanced. NH3 in renal tubular cells are excreted and bound with H+ in urine to decrease the H+. This is good for the excreting of H+ and retention of Na+ to protect from acidosis. 目录 4. Lactate cycle: In muscle lactate can by produced by glycolysis. Gluconeogenic capacity of muscle is very low, so lactate diffused into blood and transported to the liver. In the liver, glucose is synthesized from lactate by gluconeogenesis. After glucose is released into blood, it can be taken up by muscle, which formed a cycle named Lactate cycle or Cori cycle. Because the enzymes in the liver and muscle are different, they could contribute to the formation of lactate cycle. 目录 Lactate Glucose cycle (Cori cycle) Glucose gluconeo genesis glycolysis Pyruvate Pyruvate NADH NADH NAD+ Lactate Lactate NAD+ Lactate Blood muscle 】【 Low gluconeogenesis Without G-6-P Liver 【 glucose/mus cle glycogen Active gluconeogenesis With G-6-P 】 目录 Lactate cycle consumes energy: 6 ATP are needed when 2 lactate are generated to 1 glucose. Significance: Avoid waste of lactate Protect from acidosis caused by accumulation of lactate 目录 Part VII Metabolism of Other Monose 目录 Fructose, galactose and mannose enter the glycolysis through converting into intermediate products of glycolytic pathway. 目录 Part VIII The Definition, Level and Regulation of Blood Glucose 目录 The definition and level of blood glucose Blood glucose: the glucose in the blood The level of blood glucose: Normal blood glucose :3.89~6.11mmol/L 目录 The physiological significance of the maintenance of blood glucose level Ensure the energy supply of some important organs, especially the organs which is dependent on glucose energy supply. The brain depend on glucose because they cannot oxidize alternative fuels. Erythrocytes depend on glycolysis because they have no mitochondria. Bone marrow and nerve tissue are used to utilized glucose because their active metabolism. 目录 1. The resource and outlet of blood glucose is relative balanced. Food carbs Digestion/ absorption CO2 + H2O oxidation, lysis Glycogen synthesis lysis Liver glycogen Blood glucose liver(muscle) glycogen Pentose phosphate pathway Other carbs gluconeogenesis Anabolism of fat, amino acid Non-carbohydrate substrate Fat, amino acid 目录 2. The level of blood glucose is mainly regulated by hormone The maintenance of stable levels of glucose in the blood is one of the most finely regulated homeostatic mechanisms that involves the liver, extrahepatic tissues, and several hormones. Different metabolic pathways among different organs could be regulated coordinately to meet the variable needs of body, it depend on the regulation of hormone. The key enzymes involved in glucose metabolisms are regulated by different kinds of hormone. 目录 The hormones regulate blood glucose Decrease blood glucose:insulin Increase blood glucose: glucagon glucocorticoids epinephrine 目录 1. Insulin is the only hormone which can decrease blood glucose. Insulin is the only hormone which can decrease blood glucose and promote synthesis of glycogen, lipids, and proteins. Insulin is released in response to hyperglycemia. 目录 Mechanism of insulin ① Insulin enhance glucose transport into adipose tissue and muscle by recruitment of glucose transporters from the interior of the cells to the plasma membrane. ② Insulin reduces the cAMP level in the liver by activating a cAMPdegrading phosphodiesterase. By stimulating the glucoseconsuming pathways and inhibiting the glucose-producing pathways in the liver, insulin lower the blood glucose level. ③ Insulin activate pyruvate dehydrogenase by activating pyruvate dehydrogenase phosphatase, to accelerate oxidation of pyruvate to Acetyl-CoA, resulting the aerobic oxidation of carbohydrates. ④ Insulin inhibit gluconeogenesis in liver by decreasing the synthesis of PEP-carboxykinase and promoting the entrance of amino acid into muscle and protein synthesis. ⑤ Insulin slow the speed of fat mobilization through inhibiting the hormone-sensitive lipase in fat. 目录 2. Different hormone increase blood glucose under different conditions. 1.Glucagon is the main hormone which increase blood glucose in vivo. Glucagon is released in response to hypoglycemia or high level of amino acid in blood. 目录 Mechanism of glucagon 目录 Insulin and glucagon not only regulate blood glucose, but also play important role on the metabolism regulation of three nutriments. The change of carbohydrates, fat and amino acid metabolism is decided by the insulin/glucagon ratio. The secretion of two hormones is opposite. e.g. hyperglycemia stimulate the release of insulin, but inhibit the release of glucagon. 目录 2. Glucocorticoids cause the increase of blood glucose Mechanism of glucocorticoids ① They can increase gluconeogenesis by enhancing hepatic uptake of amino acids and increasing activity of aminotransferases and key enzymes of gluconeogenesis. ② They inhibit the uptake and utilization of glucose in extrahepatic tissues. 目录 3. Epinephrine is stress hormone that increase blood glucose Mechanism of epinephrine Epinephrine is secreted as a result of stress stimuli and lead to glycogenolysis in the liver and muscle owing to stimulation of phosphorylase via generation of cAMP. 目录 3. Dysfunction of carbohydrate metabolism: abnormal blood glucose and diabetes. Under normal conditions, there are a fine mechanism for the regulation of glucose metabolism to keep blood glucose from large fluctuations and sustained increase after uptake a large glucose. A healthy individual could tolerate to the uptake of a large glucose and keep blood glucose in normal level, this is called glucose tolerance. 目录 Two common symptoms of carbohydrate metabolism disorder in clinical: Hypoglycemia Hyperglycemia 目录 1. Hypoglycemia: blood glucose concentration below 3.0mmol/L Hazards of hypoglycemia: Hypoglycemia influence the function of brain because brain cells depend on the oxidation of glucose to supply energy. Hypoglycemia causes symptoms such as dizziness or light-headedness, weakness, palmus even faint which is called hypoglycemic shock. It can lead to death if we do not give the patient intravenous glucose supplement. 目录 The reasons of hypoglycemia: ① Dysfunction of pancreas: hyperfunction of pancreas β-cell, hypofunction of pancreas α-cells; ② Dysfunction of liver: liver cancer, glycogen storage disease; ③ Dyscrinism: hypofunction of Pituitary, hypofunction of adrenal cortex; ④ Tumor: stomach cancer; ⑤ Fasting and starve; 目录 2. hyperglycemia: fasting blood glucose exceed 6.9mmol/L In clinical, fasting blood glucose exceed 5.6 ~ 6.9mmol/L is called hyperglycemia. When blood glucose concentration exceed the tubular reabsorption capacity (renal glucose threshold), hyperglycemia caused glucosuria. Persistence hyperglycemia and glucosuria, especially fasting blood glucose and glucose-tolerance are higher than the normal range, it is often caused by diabetes mellitus. 目录 The reasons of hyperglycemia: ① Diabetes; ② Genetic defects in insulin receptor; ③ chronic nephritis, nephrotic syndrome ④ Physiological hyperglycemia and glucosuria; 目录 3. Diabetes is a common disease of carbohydrate metabolism disorder Diabetes, caused by a deficiency in the secretion or action of insulin, is a relatively common disease. 目录 Two types of diabetes: Type Ⅰ (insulin-dependent ) Type Ⅱ (non-insulin-dependent ) 目录 Problems: 1.The process of glutamate completely oxidized into CO2 and H2O and the ATP ? 2.Which metabolism pathway that G-6P could enter in liver or muscle? G(replenish blood glucose) 6-Phosphoglucono-lactone (enter pentose phosphate pathway) G-6-P F-6-P (enter glycolysis) G-1-P UDPG Gn(Glycogen synthesis) 目录