Carbohydrate Metabolism Lecture Notes PDF

FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Carbohydrate...

FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Carbohydrate Metabolism Lec Module 4 Far Eastern University IAS – Dept. of Mathematics Biochemistry Cluster 1 Outline of the Topics Overview of Metabolism Definitions Catabolism & Anabolism Carbohydrate Metabolism Carbohydrate Digestion & Absorption Glycolysis & Fates of Pyruvate Gluconeogenesis Glycogenesis Glycogenolysis 2 1 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Overview of Metabolism 3 Overview of Metabolism Metabolism is the overarching term for all the biochemical reactions involved in maintaining the dynamic state of the cell. Molecules that are the products and substrates in these reactions are referred to as intermediates or metabolites. 4 2 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Catabolism & Anabolism Metabolism and the reactions involved are classified into two: Catabolism – the breakdown of molecules to produce energy; degradative reactions Anabolism – the synthesis of molecules that consume energy; synthetic reaction Consecutive biochemical/metabolic reactions are called pathways. Catabolic pathways lead to the production of energy, e.g. glycolysis Anabolic pathways lead to the synthesis of biomolecules., e.g. gluconeogenesis 5 Carbohydrate Metabolism 6 3 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Carbohydrate Digestion Route Activity Enzyme Present Absorption Mouth Food is masticated in the Salivary amylases – Minimal absorption as oral cavity and turn into hydrolysis of α-glycosidic food is swallowed quickly bolus upon entering the linkages in starch and esophagus. glycogen to produce smaller polysaccharides and disaccharide – maltose Stomach Salivary amylase gets No carbohydrate It reacts with the inactivated because of digesting enzymes hydrochloric acid (HCl) in stomach acidity present in stomach the stomach as well as other enzymes and is turned into chyme. Some amino acid absorption takes place here. 7 Carbohydrate Digestion Route Activity Enzyme Present Absorption Small Once it enters the small Pancreatic α-amylase Most of the absorption Intestine intestine, there is a breaks down occurs in the small and release of bile which polysaccharide chains large intestines as the neutralized the pH of the into disaccharide food is broken down into stomach’s gastric juices, maltose individual molecules by as well as emulsify lipids the enzymes and for it to be absorbed. bacteria Outer Maltase - Converts membrane maltose to glucose of intestinal Sucrase - Converts mucosal sucrose to glucose and cells fructose Lactase - Converts lactose to glucose and galactose 8 4 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Route of Absorption Carbohydrate digestion products (glucose, galactose, and fructose) are absorbed into the bloodstream through the intestinal wall Intestinal villi are rich in blood capillaries into which the monosaccharides are actively transported. Protein carriers mediate the passage of the monosaccharides through cell membranes Galactose and fructose are converted to products of glucose metabolism in the liver 9 Glycolysis Breakdown of Glucose 10 5 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Overview of Glycolysis Pathway 11 Main Points in Glycolysis Metabolic pathway by which one molecule of glucose is converted to two molecules of pyruvate (a C3 molecule). Produces ATP and NADH-reduced coenzymes Occurs in two stages - Six-carbon (Energy Investment) and three carbon (Energy Production/Payoff) stages 12 6 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Main Points in Glycolysis In many metabolic pathways, there are reactions that are known as committed steps. Many reactions in metabolic pathways are reversible. Committed steps are irreversible reactions and usually involve the addition/removal of phosphate groups or CoA. 13 Step 1: Formation of glucose 6-phosphate Phosphorylation of glucose - A phosphate group from ATP is attached to the hydroxyl group on carbon 6 of glucose Reaction is catalyzed by hexokinase Energy required is derived from ATP hydrolysis 14 7 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Step 2: Formation of fructose 6-phosphate Glucose 6-phosphate is isomerized to fructose 6-phosphate by phosphoglucoisomerase. 15 Step 3: Formation of fructose 1,6-bisphosphate Phosphorylation reaction Energy derived from ATP hydrolysis Enzyme involved – Phosphofructokinase 16 8 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Step 4: Formation of two triose phosphates C6 biphosphate is split into two C3 monophosphate species Two C3 species formed are dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. Reaction catalyzed by aldolase 17 Step 5: Formation of glyceraldehyde 3-phosphate Dihydroxyacetone phosphate is isomerized to glyceraldehyde-3-phosphate Enzyme involved - Triosephosphate isomerase 18 9 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Step 6: Formation of 1,3-bisphosphoglycerate Reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase A molecule of the reduced coenzyme NADH is a product of the reaction Source of the added phosphate is inorganic phosphate (Pi) Carboxylate ion and phosphate (Pi) are joined together to form the bisphosphate product 19 Step 7: Formation of 3-phosphoglycerate Diphosphate species is converted back to a monophosphate species An ATP-producing step – C1 high-energy phosphate group of 1,3- bisphosphoglycerate is transferred to an ADP molecule to form the ATP Enzyme involved - Phosphoglycerokinase Two ATP molecules are produced for each original glucose molecule 20 10 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Step 8: Formation of 2-phosphoglycerate Involves isomerization of 3-phosphoglycerate to 2-phosphoglycerate Phosphate group moved from carbon 3 to carbon 2 Enzyme involved – Phosphoglyceromutase 21 Step 9: Formation of phosphoenolpyruvate Alcohol dehydration reaction - Results in another high-energy phosphate group containing compound Enzyme involved - Enolase 22 11 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Step 10: Formation of pyruvate High energy phosphate group is transferred from phosphoenolpyruvate to an ADP molecule to produce ATP and pyruvate Enzyme involved - Pyruvate kinase Two ATP molecules are produced for each original glucose molecule 23 SUMMARY OF ATPs IN GLYCOLYSIS Overall equation for glycolysis: 1 glucose + 2NAD+ + 2ADP + 2Pi 2 pyruvate + 2NADH + 2ATP + 2H+ + 2H2O 24 12 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Regulation of Glycolysis Step 1 - Conversion of glucose to glucose 6-phosphate by hexokinase Hexokinase is inhibited by glucose 6-phosphate (feedback inhibition) Step 3 - Conversion of fructose 6-phosphate to fructose 1,6- bisphosphate by phosphofructokinase. High concentrations of ATP and citrate inhibit enzyme activity Step 10 - Conversion of phosphoenolpyruvate to pyruvate by pyruvate kinase Enzyme is inhibited by high ATP concentrations Both pyruvate kinase (Step 10) and phosphofructokinase (Step 3) are allosteric enzymes 25 Fates of Pyruvate Pyruvate is most commonly metabolized in one of three ways, depending on the type of organism and the presence or absence of O2. Pyruvate metabolism provides continuous supply of NAD+ for glycolysis If no oxygen is present to reoxidize NADH to NAD+, then another way must be found to reoxidize it. 26 13 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Fates of Pyruvate 1. Oxidation to Acetyl-CoA Takes place under aerobic (oxygen-rich) conditions. Catalyzed by pyruvate dehydrogenase complex Pyruvate from glycolysis crosses the two mitochondrial membranes and enters the mitochondrial matrix. Acetyl CoA molecules from pyruvate enter the citric acid cycle. Most pyruvate formed during glycolysis is converted to acetyl CoA. 27 Fates of Pyruvate 2. Lactate Fermentation (Reduction to Lactate) Takes place under anaerobic (oxygen-deficient) conditions in muscles Catalyzed by lactate dehydrogenase Increases the concentration of lactate and H+ in muscle tissue Provides NAD+ for glycolysis Lactate is converted back to pyruvate when aerobic conditions are reestablished 28 14 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Fates of Pyruvate 3. Ethanol Fermentation Takes place under anaerobic (oxygen-deficient) conditions in simple organisms, e.g. yeast, bacteria Two step process catalyzed by pyruvate decarboxylase and alcohol dehydrogenase Produces NAD+, ethanol and CO2 29 Gluconeogenesis Synthesis of Glucose 30 15 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Gluconeogenesis Pathway by which glucose is synthesized from noncarbohydrate materials. Gluconeogenesis and glycolysis are not exact opposites Non-carbohydrate starting materials for gluconeogenesis include: – Pyruvate – Lactate (from muscles and from red blood cells) – Glycerol (from triacylglycerol hydrolysis) – Glucogenic amino acids (from dietary protein hydrolysis or from muscle protein during starvation) 31 Gluconeogenesis About 90% of gluconeogenesis takes place in the liver Conditions in which gluconeogenesis occurs: – To replenish depleted liver glycogen stores – To convert lactate (produced by strenuous exercise) back to glucose – To maintain blood glucose level when glycogen stores have been depleted Pyruvate to glucose conversion requires the expenditures of 4 ATP and 2 GTP Gluconeogenesis occurs at the expense of other ATP-producing metabolic processes 32 16 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Enzymes of Gluconeogenesis Majority of enzymes used in glycolysis are also used in gluconeogenesis, except for enzymes used in the irreversible, committed steps of glycolysis: – Pyruvate Kinase (Glycolysis Step 10) – Phosphofructokinase (Glycolysis Step 3) – Hexokinase (Glycolysis Step 1) In gluconeogenesis, these steps are bypassed by reactions catalyzed by gluconeogenic enzymes. Formation of one molecule of glucose from pyruvate requires 4 ATP, 2 GTP, and 2 NADH. 33 Enzymes of Gluconeogenesis Pyruvate Carboxylase & PEP Carboxykinase - bypasses Step 10 of glycolysis catalyzed by pyruvate kinase - converts pyruvate to phosphoenalpyruvate - Pyruvate Carboxylase: carboxylation of pyruvate to form oxaloacetate - PEP Carboxykinase (PEPCK): decarboxylation and phosphorylation of oxaloacetate to form phosphoenolpyruvate 34 17 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Enzymes of Gluconeogenesis Fructose-1,6-bisphosphatase - bypasses Step 3 of glycolysis catalyzed by phosphofructokinase - converts fructose-1,6-bisphosphate to fructose-6-phosphate - Fructose-1,6-bisphosphatase (FBPase-1,6): dephosphorylation of fructose- 1,6-bisphosphate (FBP) to fructose-6-phosphate (F6P) 35 Enzymes of Gluconeogenesis Glucose-6-phosphatase - bypasses Step 1 of glycolysis catalyzed by hexokinase - converts glucose-6-phospahte to glucose - Glucose-6-phosphatase: dephosphorylation of glucose-6-phosphate (G6P) to glucose 36 18 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Glycogenesis Synthesis of Glycogen 37 Glycogen Branched polymeric form of glucose Storage form of carbohydrates in humans and animals – In muscle, it is the source of glucose for glycolysis – In liver tissue, it is the source of glucose required to maintain normal blood glucose levels 38 19 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Glycogenesis Pathway to synthesize glycogen for glucose storage Takes place in the liver and muscles when there is an excess of glucose 39 Step 1: Formation of glucose 1-phosphate Starting material is glucose 6-phosphate (available from the first step of glycolysis) Phosphoglucomutase catalyzes the isomerization from G6P to G1P 40 20 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Step 2: Formation of UDP-glucose High-energy compound UTP (uridine triphosphate) activates glucose 1- phosphate to form uridine diphosphate glucose (UDP-glucose) Catalyzed by glucose-1-phosphate uridyltransferase (also referred as UDP- glucose pyrophosphorylase) 41 Step 3: Glucose transfer to a glycogen chain Glucose unit of UDP-glucose is attached to the end of a glycogen chain and UDP is produced Catalyzed by glycogen synthase UDP reacts with ATP to form UTP and ADP Adding one glucose unit to a glycogen chain requires the investment of two ATP molecules 42 21 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Glycogenolysis Breakdown of Glycogen 43 Glycogenolysis Pathway for breaking down glycogen to produce glucose molecules when blood sugar levels are low Produces glucose-6-phosphate that can directly enter glycolysis 44 22 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Step 1: Phosphorylation of Glucose Terminal glucose molecule of glycogen is phosphorylated and removed from glycogen chain to produce glucose-1-phosphate Catalyzed by glycogen phosphorylase Cleaves α(1à4) glycosidic bond and phosphorylation uses inorganic phosphate (Pi), not ATP 45 Step 2: Glucose-1-phosphate Isomerization Glucose-1-phosphate is isomerized to glucose-6-phosphate Catalyzed by phosphoglucomutase 46 23 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 Relationships Among Four Common Metabolic Pathways That Involve Glucose 47 WORKSHEET! ANSWER WORKSHEET 4: CARBOHYDRATE METABOLISM ON CANVAS 48 24 FEU Biochemistry Property. All forms of replication will be prohibited. Seek permission from Ms.Jessa Natividadad and Ms. Erika Viloria 8/13/24 END! 49 25