Carbohydrates Carbohydrates Are the Most Abundant Organic Molecules in Nature. the Empiric Formula for Many of the Simpler Carbo
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Ahmed Ali Hussein BVMS, PhD Scientific degree (Lecture ), Department of Physiology, Biochemistry, and Pharmacology College of Veterinary Medicine, University of Mosul, Mosul, Iraq https://orcid.org/ 0000-0001-7680-4791 https://www.researchgate.net/profile/ Ahmed Hussein Carbohydrate Metabolism | Part I | 2nd year 2019 Carbohydrates Carbohydrates are the most abundant organic molecules in nature. The empiric formula for many of the simpler carbohydrates is (CH2O)n , hence the name “hydrate of carbon.” Example: glucose (C6 H12O6). Monosaccharides (simple sugars) containing an aldehyde group are called aldoses and those with a keto group are called ketoses. Examples of an aldose (A) and a ketose (B) sugar. Metabolism:- which is the sum of all the chemical changes occurring in a cell, a tissue, or the body. Most pathways can be classified as either catabolic (degradative) or anabolic (synthetic). Catabolic reactions break down complex molecules, such as proteins, polysaccharides, and lipids, to a few simple molecules, for example, CO2, NH3 (ammonia), and water. Anabolic pathways form complex end products from simple molecules, for example, the synthesis of the polysaccharide, glycogen, from glucose. Biochemistry | Carbohydrate Metabolism | Dr. Ahmed Ali Hussein Page | 1 Functions of carbohydrates :- They have a wide range of functions, including providing a significant fraction of the energy in the diet of most organisms, acting as a storage form of energy in the body, and serving as cell membrane components that mediate some forms of intercellular communication. Carbohydrates also serve as a structural component of many organisms, including the cell walls of bacteria, the exoskeleton of many insects, and the fibrous cellulose of plants. Classification and Structure of Carbohydrates :- 1. Monosaccharides . 2. Disaccharides. 3. Oligosaccharides 4. Polysaccharides. 1. Monosaccharides :- Monosaccharides (simple sugars) can be classified according to the number of carbon atoms they contain. Examples of some monosaccharides commonly found in humans. 2. Disaccharides. Disaccharides contain two monosaccharide units; Important disaccharides include lactose (galactose + glucose), sucrose (glucose + fructose), maltose (glucose + glucose). Biochemistry | Carbohydrate Metabolism | Dr. Ahmed Ali Hussein Page | 2 A glycosidic bond between two hexoses producing a disaccharide. 3. Oligosaccharides contain from three to about ten monosaccharide units, 4. Polysaccharides. Polysaccharides contain more than ten monosaccharide units, and can be hundreds of sugar units in length. Important polysaccharides include branched glycogen (from animal sources) and starch (plant sources) and unbranched cellulose (plant sources); each is a polymer of glucose. The bonds that link sugars are called glycosidic bonds. Biochemistry | Carbohydrate Metabolism | Dr. Ahmed Ali Hussein Page | 3 Digestion and absorption of Carbohydrates :- The mechanical and chemical digestion of carbohydrates begins in the mouth. Chewing, also known as mastication, crumbles the carbohydrate foods into smaller pieces. The salivary glands in the oral cavity secrete saliva that coats the food particles. Saliva contains the enzyme, salivary amylase. This enzyme breaks the bonds between the monomeric sugar units of disaccharides, oligosaccharides, and starches. The salivary amylase breaks down amylose and amylopectin into smaller chains of glucose, called dextrins and maltose. Amylase is sensitive to pH and thus is inhibited in the acidic environment of the stomach. The pancreas releases pancreatic enzyme called pancreatic amylase, which starts again the breakdown of dextrins into shorter and shorter carbohydrate chains. This enzymes, known collectively as disaccharides, are sucrose, maltose and lactose. Sucrase breaks sucrose into glucose and fructose molecules. Maltase breaks the bond between the two glucose units of maltose, and lactase breaks the bond between galactose and glucose. Once carbohydrates are chemically broken down into single sugar units they are then transported into inside of intestinal cells. Then the cells in the small intestine have membranes that contain many transport proteins in order to get the monosaccharides and other nutrients into the blood where they can be distributed to the rest of the body. The first organ to receive glucose, fructose and galactose is the liver. The liver takes them up and converted galactose to glucose, breaks fructose into even smaller carbon- containing unites, and either stores glucose as glycogen or exports it back to the blood. Summary Mouth :- Salivary amylase converts polysaccharide to smaller saccharides . Stomach :- Low PH stops action of salivary amylase. Duodenum :- Pancreatic amylase converts polysaccharide to maltose and isomaltose. Small intestine :- Disaccharides are digested and absorbed. Biochemistry | Carbohydrate Metabolism | Dr. Ahmed Ali Hussein Page | 4 The three principle monosaccarides resulting from the digestion are :- Glucose, Fructose and Galactose. Absorption: Once carbohydrates are digested, the products must be absorbed and transported to the portal circulation. Digestion and absorption are typically coupled. Glucose absorption occurs in the small intestine via the SGLT-1 transporter (sodium glucose co-transporter). Fructose absorption is completed via the GLUT5 transporter by facilitated diffusion. Glucose and galactose are actively transported from the small intestine lumen by the sodium glucose transporter (SGLT-1) located in the brush border of the small intestine. Biochemistry | Carbohydrate Metabolism | Dr. Ahmed Ali Hussein Page | 5 Biochemistry | Carbohydrate Metabolism | Dr. Ahmed Ali Hussein Page | 6 Biochemistry | Carbohydrate Metabolism | Dr. Ahmed Ali Hussein Page | 7 Major Pathways in carbohydrate metabolism Glucose is oxidized by glycolysis, an energy-generating pathway that converts is to pyruvate. In the absence of oxygen, pyruvate is converted (reduced) to lactate, so it can allow the production of ATP in tissues that lack mitochondria example RBC or in exersizing skeletal muscules. When oxygen is present, pyruvate is further degraded to form acetyl-CoA. it occurs in cells with mitochondria and the end product is pyruvate. Significant amounts of energy in the form of ATP can be extracted from acetyl-CoA by the citric acid cycle and the electron transport system. Excess glucose is converted to its storage form, glycogen, by glycogenesis. When glucose is needed as a source of energy or as a precursor molecule in biosynthetic processes, glycogen is degraded by glycogenolysis. Glucose can be converted to ribose-5-phosphate (a component of nucleotides) and NADPH (a powerful reducing agent) by means of the pentose phosphate pathway. Metabolism of CHO can be subdivide as following :- 1- Glycolysis pathway . 2- Citric acid cycle . ( oxidation of pyruvate to Acetyl-CoA) . 3- Glycogenesis . 4- Glycogenolysis . 5- Gluconeogenesis . 6- Hexose monophosphate shunt . Glycolysis pathway :- Found in the cytosol of all mammalian cells (to provide energy) for the metabolism of glucose to pyruvate and lactate. Glycolysis also called Embden-Meyerhof Pathway. Glycolysis is consists of 10 reactions, occurs in tow stages : 1. Glucose is phosphorylated twice and cleaved to form tow molecules of glyceraldehyde-3-phosphate (G-3-P). The tow ATP molecules consumed during this stage are like an investment, because this stage creates the actual substrates for oxidation in form that is trapped inside the cell. 2. Glyceraldehyde-3-phosphate is converted to pyruvate. Four ATP and tow NADH molecules are produced. Because tow ATP were consumed in stage 1, the net production of ATP per glucose molecule is 2.and (+2 NADH) Biochemistry | Carbohydrate Metabolism | Dr. Ahmed Ali Hussein Page | 8 The glycolytic pathway can be summed up in the following equation : + + D-Glucose + 2 ADP + 2 Pi + 2 NAD 2 Pyruvate + 2 ATP + 2 NADH + 2H + 2 H2O Glycolysis is controlled by 3 enzymes catalyzing non- equilibrium reactions : 1- Hexokinase or glucokinase . (1) 2- Phosphofructokinase (PFK) . (3) 3- Pyruvate kinase . (10) All these enzymes found in the cytoplasm. Biochemistry | Carbohydrate Metabolism | Dr. Ahmed Ali Hussein Page | 9 The reactions of the Glycolytic pathway 1. Synthesis of glucose-6-phosphate. Immediately after entering a cell, glucose and other sugar molecules are phosphorylated. Phosphorylation prevents transport of glucose out of the cell and increases the reactivity of the oxygen in the resulting phosphate ester. Hexokinases (glucokinase) catalyze the phosphorylation of hexoses in all cells in the body. ATP, a cosubstrate in the reaction, is complexed with Mg 2+ . The reaction is irreversible. 2. Conversion of glucose-6-phosphate to fructose-6-phosphate. During reaction 2 of glycolysis, the open chain form of the aldose glucose-6-phosphate is converted to the open chain form of the ketose fructose-6-phosphate by phosphoglucose isomerase (PGI) in a readily reversible reaction: Biochemistry | Carbohydrate Metabolism | Dr. Ahmed Ali Hussein Page | 10 3.The phosphorylation of fructose-6-phosphate. Phosphofructokinase-1 (PFK-1) irreversibly catalyzes the phosphorylation of fructose-6-phosphate to form fructose-1,6-bisphosphoate: 4. Cleavage of fructose-1,6-bisphosphate. Stage 1 of glycolysis ends with the cleavage of fructose- 1,6-bisphosphate into tow three-carbon molecules: glyceraldehydes-3-phosphate (G-3-P) and dihydroxyacetone phosphate (DHAP).the name of enzyme is aldolase. 5. The interconversion of glyceraldehyde-3-phosphate