Carbohydrate Metabolism Prepared by: Group 3 Learning Objectives At the end of the lesson, the students should be able to: • • To define metabolism and explain its significance in living organism, To discuss the specific functions and locations of each metabolic phase Carbohydrate Carbohydrates are a group of organic compounds containing a ratio of one carbon to two hydrogen atoms to one oxygen atom. It can be represented by the stoichiometric formula (CH20)N, where n is the number of carbons in the molecule. Carbohydrate, in Greek word is “saccharide” which means sugar. Glucose is the most abundant carbohydrate in the human body that has a chemical formula of C6H12O6 01 Introduction to Metabolism Design, Phases, Stages, and Regulation Metabolism • • • Metabolism consists of a series of reactions that occur within cells of living organisms to sustain life. Refers to the totality of all chemical reactions within an organism. Carbohydrate metabolism is a fundamental biochemical process that ensures a constant supply of energy to the living cells. Metabolic Pathways Catabolism or destructive metabolism: metabolism in which larger molecules are broken down into smaller molecules. Anabolism or constructive metabolism: metabolism in which smaller molecules combine to form larger molecules. Basic Design of Metabolism PHASES OF METABOLISM Phase 1: Glycolysis • • • Glycolysis occurs within the cytoplasm of the cell and serves as the preliminary stage of carbohydrate metabolism. Glucose, a six-carbon sugar, is decomposed into two molecules of the three-carbon compound pyruvate. ATP is both produced and consumed at different stages, while NADH is also generated. Phase 2: The citric acid cycle • • • • It is also known as the Krebs cycle, is an elaborate metabolic pathway that takes place within the mitochondria and utilizes the byproducts of glycolysis for additional processing. Pyruvate-derived acetyl-CoA is introduced into the citric acid cycle. Carbon dioxide is liberated, accompanied by the production of NADH and FADH2. By means of substrate-level phosphorylation, ATP is produced. Phase 3: Oxidative phosphorylation • • • This process occurs within the inner mitochondrial membrane and entails the synthesis of ATP and the transfer of electrons via the electron transport chain (ETC). Transfer of high-energy electrons from FADH2 and NADH via protein complexes in the ETC. A proton gradient is generated by the movement of electrons, and ATP is produced. STAGES OF CARBOHYDRATE METABOLISM STAGE 1: Digestion Location: GI TRACT STAGE 2: Acetyl formation Location: Mitochondria End products of digestion are broken down to give 2 Carbon units of Acetyl CoA STAGE 3: Citric Acid Cycle Location: Mitochondrial Matrix Acetyl CoA acts as a fuel source for the Citric Acid Cycle producing high energy electron carriers NADH and FADH2 STAGE 4: Electron Transport Chain & Oxidative Phosphorylation Location: Inner Mitochondrial Membrane High energy electrons from NADH and FADH2 fuel proton pumps within the Inner Mitochondrial Membrane leading to the movement and accumulation of protons within the intermembrane space. Regulation Metabolism is governed by complex cellular processes that maintain a delicate equilibrium between energy production and utilization. Hormones such as insulin and glucagon have significant roles in regulating glucose levels. In addition, enzymes, feedback loops, and gene expression play a role in maintaining metabolic homeostasis. Metabolism regulation can be influenced by various factors such as dietary choices, level of physical activity, and overall health. Digestion and Absorption of Carbohydrates WHAT IS DIGESTION AND ABSORPTION? • Digestion is the process of breaking large, insoluble food molecules into smaller molecules for absorption into the bloodstream. This process involves the use of many digestive fluids and enzymes such as saliva, mucus, bile and hydrochloric acid, among others. • Absorption is the process of the absorbing or assimilating substances into the cells or across the tissues and organs through the process of diffusion or osmosis. Carbohydrates are one of the essential nutrients in the human diet. There are two types of carbohydrates that can be digested by the human digestive system– sugar and starch. Sugar is broken down in the gastrointestinal tract by the small intestine and three enzymes present in the mouth, namely, Lactase, Sucrase, and Maltase. In the same way, starch is broken down with the help of the Amylase enzymes which are present in the mouth and the stomach. After digestion, carbohydrates are absorbed in the small intestine with the help of minute finger-shaped projections known as Villi. Digestion and absorption of From the Mouth to the Stomach Carbohydrates ● The mechanical and chemical digestion of carbohydrates begins in the mouth. Chewing, also known as mastication, crumbles the carbohydrate foods into smaller and smaller pieces. From the Stomach to the Small Intestine ● The chyme is gradually expelled into the upper part of the small intestine. Upon entry of the chyme into the small intestine, the pancreas releases pancreatic juice through a duct. This pancreatic juice contains the enzyme, pancreatic amylase, which starts again the breakdown of dextrins into shorter and shorter carbohydrate chains. Additionally, enzymes are secreted by the intestinal cells that line the villi. These enzymes, known collectively as disaccharides, are Absorption of Carbohydrates ● The end products of sugars and starches digestion are the monosaccharides glucose, fructose, and galactose. Glucose, fructose, and galactose are absorbed across the membrane of the small intestine and transported to the liver where they are either used by the liver, or further distributed to the rest of the body. Catabolic Pathways And Absorption Catabolic pathways (catabolism) break down foodstuffs into smaller molecules, thereby generating both a useful form of energy for the cell and some of the small molecules that the cell needs as building blocks. Glycolysis In glycolysis (from the Greek glykys, meaning “sweet,” and lysis, meaning “splitting”). Glycolysis is a series of reactions that extract energy from glucose by splitting it into two three-carbon molecules called pyruvates. Glycolysis takes place in the cytosol of a cell, and it can be broken down into two main phases: Energy-requiring phase during the energy-requiring phase of glycolysis. Two ATPs are spent to form an unstable sugar with two phosphate groups, which then splits to form two three-carbon molecules that are isomers of each other. Step 1. A phosphate group is transferred from ATP to glucose, making glucose-6phosphate. Step 2. Glucose-6-phosphate is converted into its isomer, fructose-6-phosphate. Step 3. A phosphate group is transferred from ATP to fructose-6-phosphate, producing fructose-1,6-bisphosphate. This step is catalyzed by the enzyme phosphofructokinase. Step 4. Fructose-1,6-bisphosphate splits to form two three-carbon sugars: dihydroxyacetone phosphate DHAP and glyceraldehyde-3-phosphate. They are isomers of each other, but only one—glyceraldehyde-3-phosphate—can directly continue through the next steps of glycolysis. Step 5. DHAP is converted into glyceraldehyde-3-phosphate. The two molecules exist in equilibrium, but the equilibrium is “pulled” strongly downward, in the scheme of the diagram above, as glyceraldehyde-3-phosphate is used up. Thus, all of the DHAP is eventually converted. Energy-releasing phase Step 6. Two half reactions occur simultaneously: 1) Glyceraldehyde-3-phosphate (one of the three-carbon sugars formed in the initial phase) is oxidized, and 2) NAD+is reduced to NADH and H^+ The overall reaction is exergonic, releasing energy that is then used to phosphorylate the molecule, forming 1,3-bisphosphoglycerate. Step 7. 1,3-bisphosphoglycerate donates one of its phosphate groups to ADP, making a molecule of ATP and turning into 3-phosphoglycerate in the process. Step 8. 3-phosphoglycerate is converted into its isomer, 2-phosphoglycerate. Energy-releasing phase Step 9. 2-phosphoglycerate loses a molecule of water, becoming phosphoenolpyruvate (PEP). PEP is an unstable molecule, poised to lose its phosphate group in the final step of glycolysis. Step 10. PEP readily donates its phosphate group to ADP, making a second molecule of ATP. As it loses its phosphate, PEP is converted to pyruvate, the end product of glycolysis. Krebs Cycle The name we'll primarily use here, the citric acid cycle, refers to the first molecule that forms during the cycle's reactions—citrate, or, in its protonated form, citric acid. However, you may also hear this series of reactions called the tricarboxylic acid (TCA) cycle, for the three carboxyl groups on its first two intermediates, or the Krebs cycle, after its discoverer, Hans Krebs. Steps of the Krebs Cycle Step 4. The fourth step is similar to the third. In this case, it’s α-ketoglutarate that’s oxidized, reducing NAD+ to NADH and releasing a molecule of carbon dioxide in the process. The remaining four-carbon molecule picks up Coenzyme A, forming the unstable compound succinyl CoA. The enzyme catalyzing this step, α-ketoglutarate dehydrogenase, is also important in regulation of the citric acid cycle. Step 5. In step five, the CoA of succinyl CoA is replaced by a phosphate group, which is then transferred to ADP to make ATP. In some cells, GDP—guanosine diphosphate—is used instead of ADP, forming GTP—guanosine triphosphate— as a product. The four-carbon molecule produced in this step is called succinate. Steps of the Krebs Cycle Step 6. In step six, succinate is oxidized, forming another four-carbon molecule called fumarate. In this reaction, two hydrogen atoms—with their electrons— are transferred to FAD, producing FADH2. Step 7. In step seven, water is added to the four-carbon molecule fumarate, converting it into another four-carbon molecule called malate. Step 8. In the last step of the citric acid cycle, oxaloacetate—the starting fourcarbon compound—is regenerated by oxidation of malate. Another molecule of NAD+ is reduced to NADH in the process. Glycogenolysis • • • • Animals store glucose as glycogen, which is broken down in a process called glycogenolysis. Glycogenolysis is a metabolic process that converts glycogen from the muscles and liver to its monosaccharide form, glucose. Low levels of ATP within live cells trigger the glycogenolysis process. Thus, glycogen (n) is broken down into glucose-1-phosphate and glycogen (n-1) during glycogenolysis. The location of Glycogenolysis where it occurs is in the cytoplasm of cells in the liver, muscles, and adipose tissue. Steps of the Glycogenolysis Step 1. Glycogen phosphorylase and phosphorylase kinase, activated by phosphorylation, are the two main regulating enzymes of glycogenolysis. These will primarily be expressed in the brain, muscles, and liver. Step 2. Adenyl cyclase and cAMP activity in the muscle triggers the beginning of glycogenolysis. After phosphorylase kinase is bound by cAMP and transformed into its active state, phosphorylase b is changed into phosphorylase a, which ultimately catalyses glycogen degradation. Step 3. The cytosolic enzyme glycogen phosphorylase uses inorganic phosphate to cleave α1,4 bonds to catalyse the production of glucose-1phosphate from the terminals of glycogen branches. Steps of the Glycogenolysis Step 4. The enzyme phosphoglucomutase converts glucose-1-phosphate into glucose-6phosphate, which frequently ends in glycolysis. Step 5. Acid α-glucosidase, an enzyme in the lysosome, uses an autophagy-dependent mechanism to break down lysosomal glycogen. This mechanism acts as an instant source of energy during the newborn stage. Step 6. When glycogen phosphorylase enzyme reaches a branch point that is four glucose residues away from it, it transfers one of the branches to another chain, generating a new α-1,4 bond and leaving one glucose unit at the branch site later hydrolysed by α-1,6-glucosidase to produce free glucose. Hexose Monophosphate (HMP) Shunt The hexose monophosphate (HMP) shunt, also known as the pentose phosphate pathway or phosphogluconate pathway, is a metabolic pathway that runs parallel to glycolysis. This pathway produces NADPH and intermediates required for the synthesis of nucleic acids and amino acids. The pathway takes place in two distinct phases: oxidative and non-oxidative phases. Location: In humans, this pathway is most active in mammary glands, adrenal cortex, adipose tissue, erythrocytes, testes and liver. Oxidative Phase Step 1. Glucose-6-phosphate is dehydrogenated to 6-phosphoglucono-δ-lactone in the presence of glucose 6-phosphate dehydrogenase. In this reaction, one molecule of NADP+ is converted into NADPH. Step 2. 6-phosphoglucono-δ-lactone is hydrolysed into 6-phosphogluconate in the presence of 6-phosphogluconolactonase. Step 3. 6-phosphogluconate is converted into ribulose 5-phosphate in the presence of 6phosphogluconate dehydrogenase by oxidative decarboxylation. Non-Oxidative Phase Step 1. Ribulose-5-phosphate isomerises into ribose-5-phosphate in the presence of ribose-5phosphate isomerase. Step 2. Another enzyme, phosphopentose epimerase, isomerises ribulose-5-phosphate into xylulose 5-phosphate at the same time. Step 3. Transketolase enzyme transfers a carbon group from ketose (xylulose-5-phosphate) to the aldose (ribose-5-phosphate), and the products obtained are glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate. Non-Oxidative Phase Step 4. Transaldolase again transfers a carbon group from sedoheptulose 7-phosphate (ketose) to glyceraldehyde 3-phosphate (aldose), and the products obtained are erythrose 4-phosphate and fructose 6-phosphate. Step 5. A carbon from xylulose 5-phosphate is transferred to erythrose 4-phosphate in the presence of transketolase to obtain glyceraldehyde 3-phosphate and fructose 6phosphate. ANABOLIC PATHWAYS Anabolism is all metabolic reactions in which small biochemical molecules are joined together to form larger ones such as amino acidsproteins, fatty acids-lipids and monosaccharidespolysaccharides. Anabolic reactions usually require energy in order to proceed. Photosynthesis is the process by which green plants and certain other organisms convert light energy into chemical energy. It is the only biological process that can capture energy from sunlight and convert it into a chemical compound called glucose, which is used by organisms to power their daily functions. In photosynthesis, the part that can be considered an anabolic process is the Calvin cycle, also known as the light-independent reaction or the dark reaction. This is the second stage of photosynthesis, where carbon dioxide (CO2) is converted into glucose (C6H12O6) using the energy stored in ATP (adenosine triphosphate) and NADPH (nicotinamide adenine dinucleotide phosphate), which are produced during the lightdependent reaction. Process of photosynthesis 1. Light Absorption: Chlorophyll, a pigment found in the chloroplasts of plant cells, absorbs light energy from the sun. 2. Conversion of Light Energy: The absorbed light energy is used to convert water (H2O) and carbon dioxide (CO2) into glucose (C6H12O6) and oxygen (O2). This process is known as the lightdependent reaction. 3. Splitting of Water: During the lightdependent reaction, water molecules are split into hydrogen ions (H+), electrons (e-), and oxygen gas (O2). The oxygen gas is released as a Process of photosynthesis 4. Production of ATP and NADPH: The energy from the absorbed light is used to produce two important molecules: ATP (adenosine triphosphate) and NADPH (nicotinamide adenine dinucleotide phosphate). These molecules carry the energy needed for the next step. 5. Calvin Cycle: The ATP and NADPH produced in the previous step are used in the Calvin cycle, which is also known as the light-independent reaction or the dark reaction. In this cycle, carbon dioxide from the atmosphere is converted into glucose with the help of enzymes and energy from ATP and NADPH. 6. Glucose Production: The glucose produced in the Calvin cycle is used by plants as a source of energy for various cellular processes. It can also be stored as starch for later use. (No. 5 & 6) Anabolic photosynthesis 1. Carbon Fixation: The process starts with the fixation of carbon dioxide (CO2) from the atmosphere. The enzyme RuBisCO combines CO2 with a five-carbon sugar molecule called ribulose bisphosphate (RuBP) to form an unstable six-carbon molecule. This six-carbon molecule quickly breaks down into two molecules of 3phosphoglycerate (3-PGA). 2. Reduction: The 3-PGA molecules are then converted into a higher energy molecule called glyceraldehyde 3-phosphate (G3P). This conversion requires ATP (adenosine triphosphate) and NADPH (nicotinamide adenine dinucleotide phosphate), which are produced during the light-dependent reactions of photosynthesis. 3. Regeneration of RuBP: Some of the G3P molecules are used to regenerate the original RuBP molecule, which is necessary for the continuation of the Calvin cycle. This step requires additional ATP. 4. Production of Glucose: The remaining G3P molecules can be used to synthesize glucose and other organic molecules. Two G3P molecules combine to form one molecule of glucose. 5. Release of Oxygen: Throughout the process of anabolic photosynthesis, oxygen is released as a byproduct. This oxygen is a vital component for the survival of aerobic organisms. Glycogen Metabolism -Glycogen metabolism refers to the processes involved in the synthesis and breakdown of glycogen, which is a complex carbohydrate and the main storage form of glucose in animals, including humans. Glycogen serves as a readily available source of energy that can be mobilized when the body needs it. - In glycogen metabolism, the anabolic process refers to the synthesis of glycogen from glucose molecules. This process is known as glycogenesis. Is the process by which glucose molecules are converted into glycogen for storage in liver and muscle cells. It is an anabolic process that occurs when blood glucose levels are high and excess glucose needs to be stored for later use. - Glycogenesis involves the conversion of glucose-6-phosphate into glycogen through a series of enzymatic reactions. Process of Glycogenesis 1. Glucose-6-phosphate Conversion: Glucose-6-phosphate, which is derived from glucose through various metabolic pathways, serves as the precursor for glycogen synthesis. 2. Activation of Glucose-6-phosphate: Glucose-6-phosphate is first converted into glucose-1-phosphate by the enzyme phosphoglucomutase. 3. Formation of UDP-Glucose: Glucose-1phosphate is then activated by the enzyme UDP-glucose pyrophosphorylase, which converts it into UDP-glucose. This step involves the transfer of a nucleotide (UDP) to glucose-1-phosphate. Process of Glycogenesis 4. Glycogen Chain Elongation: The activated glucose molecule (UDPglucose) is added to the growing glycogen chain by the enzyme glycogen synthase. This process involves the formation of α-1,4glycosidic linkages between glucose molecules. 5. Branching: As the glycogen chain grows, branching occurs through the action of the enzyme glycogen branching enzyme. It transfers a segment of the growing chain to another position, creating α-1,6glycosidic linkages and increasing the efficiency of glycogen synthesis. Overall, the anabolic process of glycogen metabolism involves the synthesis of glycogen from glucose-6-phosphate through a series of enzymatic reactions, resulting in the formation of glycogen chains with branching structures Gluconeogenesis In gluconeogenesis, the anabolic process refers to the synthesis of glucose from non-carbohydrate precursors such as amino acids, lactate and glycerol. Gluconeogenesis is an energy-requiring pathway that occurs primarily in the liver and to a lesser extent in the kidneys. Process of gluconeogenesis: 1. Conversion of Non-Carbohydrate Precursors: Gluconeogenesis involves the conversion of various non-carbohydrate molecules, such as amino acids, lactate, and glycerol, into glucose. These molecules serve as the building blocks for glucose synthesis. 2. Reversal of Glycolytic Pathway: Gluconeogenesis essentially reverses the steps of glycolysis, which is the breakdown of glucose. However, there are three irreversible steps in glycolysis that need to be bypassed in gluconeogenesis. These steps are catalyzed by the enzymes pyruvate kinase, phosphofructokinase-1, and hexokinase/glucokinase. In gluconeogenesis, alternative enzymes, such as pyruvate carboxylase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase, are utilized to bypass these irreversible steps. Process of gluconeogenesis: 3. Synthesis of Glucose-6-Phosphate: Gluconeogenesis begins with the conversion of pyruvate, lactate, or other precursors into phosphoenolpyruvate (PEP) through various enzymatic reactions. PEP is then converted into glucose-6-phosphate (G6P) by the enzyme glucose-6-phosphatase. G6P can be further processed to produce glucose. 4. Glucose Synthesis and Release: Glucose6-phosphate is converted into glucose by glucose-6-phosphatase in the liver, allowing for the release of glucose into the bloodstream. This glucose can then be utilized by other tissues that require it for Overall, gluconeogenesis is an anabolic process that involves the synthesis of glucose from non-carbohydrate precursors. It requires energy input and the reversal of certain steps in the glycolytic pathway. Gluconeogenesis is essential for maintaining glucose homeostasis in the body, especially during periods of fasting or low carbohydrate intake. Polysaccharides are complex carbohydrates composed of long chains of monosaccharide units. They play essential roles in various biological processes, including energy storage, structural support, and cell signaling. The biosynthesis of polysaccharides involves a series of enzymatic reactions that result in the formation of long chains of monosaccharide units. •During polysaccharide biosynthesis, monosaccharide units are activated through the attachment of nucleotide diphosphates or lipid carriers. These activated forms of monosaccharides serve as donors for the subsequent addition of monosaccharide units to the growing polysaccharide chain. This stepwise addition of monosaccharide units is catalyzed by specific glycosyltransferase enzymes. •The process of polysaccharide biosynthesis requires energy input in the form of ATP or other high-energy molecules. The activated monosaccharide units are energetically linked to the growing polysaccharide chain, resulting in the formation of glycosidic linkages between the monosaccharide units. •Overall, the biosynthesis of polysaccharides is an anabolic process because it involves the synthesis of complex carbohydrates from simpler monosaccharide units. This process requires energy and the action of specific enzymes to build the polysaccharide chains THANK YOU!
