Chap 4 Metabolism of Carbohydrates
Relationship of each metabolism External substance → internal subtance Assimilation Micromolecule→Biomacromolecule Anabolism Endergonic reaction Metabolism Substance metabolism Energy metabolism Exergonic reaction Dissimilation Biomacromolecule→Micromolecule Catabolism Internal substance → External substance
Definition of carbohydrate (saccharide) Carbohydrates: Carbohydrates are polyhydroxy aldehydes or ketones, or substances that yield such compounds on hydrolysis.
classes and structure of carbohydrates: Carbohydrates are classified into four types according to their hydrolysates: • monosaccharide • oligosaccharide • polysaccharide • glycoconjugate
monosaccharide It’s the simplest of the carbohydrates that could not be hydrolyzed any more. glucose （aldohexose） fructose （ketohexose）
galactose （ aldohexose ） ribose （aldopentose）
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
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
Starch —— The most important storage polysaccharides are starch in plant cells Starch granules
hydrogen bond microfibril fiber Individual cellulose molecule • cellulose —— the skeleton of plants ß1-4linkage
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.
Part I Introduction
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 metabolic intermediate. • Structural elements of cells and tissues e.g. Carbohydrates are components of glycoprotein, proteoglycans and glycolipids.
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
Process of digestion： Starch Oral cavity α-amylase in saliva Enteric cavity α-amylase in pancreatic α-limit dextrin + isomaltose (30%) (5%) Maltose + maltotriose (40%) (25%) brush border of Intestinal epithelial cells α-limit dextrinase α-glucosidase Glucose
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.
absorption of carbohydrates • absorption position : The upper small intestine • Absorption Type ：monosaccharide
Na+ PUMP • Absorption mechanism Mucosal cells of Intestinal Portal Lumen K+ ATP ADP+Pi Na+ G cellular inner membrane Brush border Na+-dependent glucose transporter, SGLT
SGLT Lumen of small intestinal Intestinal epithelial cells portal GLUT A variety of tissue cells liver Circulation 3.Overview of carbohydrate metabolism • Glucose are transported into cells This process is dependent on glucose transporter (GLUT).
intestinal（amylase、oligase） monosaccharide α、β-amylase (glucose) TransferaseDebranching enzyme Phosphorylase Phosphorylase • Extracellular Extracellular Polysaccharide and oligosaccharide • intracellular glycogen Activation hydrolysis Branched-chain break Activation hydrolysis
aerobic conditions CO2 + H2O Carbs in food Provide energy Pyruvate Digestion absorption glycolysis anaerobic conditions lactate Bread down Synthesis of glycogen liver (muscle) glycogen glycogen PPP Gluconeogenesis Other carbs anabolism Non-sugar substances Fat, amino acid The sources and outlet of blood glucose Blood glucose
Part II Glycolysis
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
1. Glycolysis Has Two Phases: • Phase I------ glycolytic pathway: The six-carbon glucose break down into two molecules of the three-carbon pyruvate. • Phase II: Pyruvate is converted to lactate.
Phase I------ glycolytic pathway: The six-carbon glucose break down into two molecules of the three-carbon pyruvate 1. Phosphorylation of Glucose
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.
2. Conversion of Glucose 6-Phosphate toFructose 6-Phosphate
3. Phosphorylation of Fructose 6- Phosphate to Fructose 1,6-Bisphosphate • 6-phosphfructokinase-1
+ 4. Cleavage of Fructose 1,6-Bisphosphate • Aldolase
5. Interconversion of the Triose Phosphates
6. Oxidation of Glyceraldehyde 3- Phosphate to 1,3-Bisphosphoglycerate
7. Phosphoryl Transfer from 1,3- Bisphosphoglycerate to ADP The formation of ATP by phosphoryl group transfer from a substrate such as 1,3-bisphosphoglycerate is referred to as a substrate-level phosphorylation
8. Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate
9. Dehydration of 2-Phosphoglycerate to Phosphoenolpyruvate
ADP ATP K+ Mg2+ pyruvate kinase Phosphoenolpyruvate Pyruvate 10. Transfer of the Phosphoryl Group from Phosphoenolpyruvate to ADP
NADH + H+ NAD+ Lactate dehydrogenase (LDH) Pyruvate Lactate Phase II:Pyruvate is converted to lactate. NADH+H+needed in this reaction is provided by Oxidation of Glyceraldehyde 3-Phosphate in step 6 of glycolytic pathway.
E1 E2 Glu G-6-P F-6-P F-1, 6-2P ATP ADP ATP ADP Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate NAD+ E1:Hexokinase NADH+H+ E2: Phosphofructokinase-1 2×1,3-Bisphosphoglycerate E3:Pyruvate kinase ADP ATP 2× 3-Phosphoglycerate lactate NAD+ 2× 2-Phosphoglycerate NADH+H+ ATP ADP 2×pyruvate 2× Phosphoenolpyruvate E3 Glycolysis
ATP ATP ADP ADP G G-6-P Hexokinase F-6-P F-1,6-2P Phosphofructokinase-1 ADP ATP PEP Pyruvate Pyruvate kinase Summary of glycolysis • Position of glycolysis：cytoplasm • Glycolysis is an anaerobic processthrough which ATP is synthesized . • There are three irreversible steps in the process.
Method and Quantity of energy-producing: Method： substrate-level Phosphorylation Quantity of ATP：From G2×2-2= 2ATP From Gn2×2-1= 3ATP • Fates of lactate: Lactate is released into blood and metabolized in liver Decomposition Cori cycle（glyconeogenesis）
galactose galactokinase UDP-galactose Glu Mannose ATP ADP hexokinase G-6-P Glucose 1-phosphate mutase Mannose 6-phosphate mutase F-6-P ATP hexokinase Fructose ADP F-1,6-2P Pyruvae Many hexose besides glucose meet their catabolic fate in glycolysis, after being transformed into hexosephosphate
①Hexokinase ②Phosphofructokinase-1 ③Pyruvate kinase ① allosteric regulation ② covalent modification 2. Regulation of Glycolysis: 3 key enzymes Key Enzymes Method of regulation
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）
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.
AMP Citrate Glucagon – + ATP cAMP 6-PFK-2 PFK-2 （active） FBP-2 （inactive） ATP Activate F-2,6-2P FBPase-2 Pi P P ADP PFK-2 （inactive） FBP-2 （active） –/+ Pi + + – + + AMP Citrate Phosphoprotein phosphatase F-6-P PKA ATP PFK-1 ADP PKA：protein kinase A F-1,6-2P
GlucogenFat Protein GlucoseFatty acie＋ Glycerine Amino acid Ⅱ Acetyl-CoA Oxaloacetate Citrate Malate α-Ketoglutarate Ⅲ Succinate CO2 Oxidative phosphorylation Succinyl-CoA 2H＋ ADP＋Pi ATP
2. Pyruvate kinase is the second regulation point of glycolysis • Allosteric regulation • allosteric activator：F-1,6-2P • allosteric inhibitor：Alanine; ATP.
P PKA, CaM kinase Glucagon • Covalent modification regulation Pi phosphoprotein phosphatase Pyruvate kinase Pyruvate kinase （active） （inactive） ATP ADP PKA：protein kinase A CaM: calmodulin