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MLAB 2401: Clinical Chemistry Keri Brophy-Martinez CARBOHYDRATE OVERVIEW Introduction 2  Organisms rely on the oxidation of complex organic compounds to obtain energy  Three general types of compounds provide chemical energy to our cells Lipids=Fats  Amino acids = Proteins  Carbohydrates= Sugars, starches  Carbohydrates 3  Major food source & energy supply of body  Primary source of energy for brain, erythrocytes, retinal cells  Depending on individual diet, 50-90% of the body's carbohydrate intake is in the form of      Grains - cereals, bread Starchy vegetables - potatoes Legumes - beans, peanuts other sources = sugar, molasses, lactose from milk, fructose from fruit Stored primarily as liver and muscle glycogen Description and Classification of Carbohydrates  Contain C, H and O molecules  Contain a C=O (ketone) and an –OH(aldehyde) functional group  Classification  Based on certain properties The size of the base carbon chain  Location of the CO functional group  Number of sugar units  Stereochemistry of compound  Chemical Properties 5  Some ( not all ) carbs are reducing substances (donate electrons)    Chemical reduction of other substances These sugars must contain an aldehyde or ketone group Reducing sugars Glucose  Maltose  Lactose  Fructose  Galactose   Sucrose is not a reducing substance Carbohydrate Metabolism  Glucose is primary energy source  Nervous tissue can not concentrate or store carbohydrates, so a steady supply of glucose is needed  Once the level of glucose falls below a certain range, normal function is impaired Carbohydrate Breakdown Dietary Carbohydrates Dextrins/ Maltose • Mouth • Salivary amylase • Stomach/Intestines • Pancreatic amylase • Absorption into intestinal mucosa • Delivered to liver Monosaccharide Carbohydrate Breakdown  Ultimate Goal  Convert glucose to CO2 and water with ATP as a by-product  Possible channels  Converted to liver glycogen and stored  Metabolized to CO2 and H2O  Converted to keto-acids, amino acids, and proteins  Converted to fats and stored in adipose tissue Biochemical Pathways in Carbohydrate Breakdown  Embden-Meyerhoff pathway Converts glucose to pyruvate/lactate  Primary energy source for humans   Hexose monophosphate shunt Oxidizes glucose to ribose and CO2  Produces NADPH as an energy source   Glycogenesis  Converts glucose to glycogen Carbohydrate Metabolism 10  Glycolysis – the conversion of glucose and other hexoses into lactate or pyruvate  Breakdown of glucose for energy production  Glycogenesis – the conversion of glucose to glycogen usually in liver & muscle  Excess glucose is converted and stored as glycogen  High concentrations of glycogen in liver and skeletal muscle  Glycogen is a quickly accessible storage form of glucose  Carbohydrate Metabolism 11  Glycogenolysis – the breakdown of glycogen to form glucose Glycogenolysis occurs when plasma glucose is decreased  Occurs quickly if additional glucose is needed  Controlled by hormones & enzymes   Gluconeogenesis – the formation of glucose from non-carbohydrate sources, such as amino acids, glycerol & fatty acids into glucose  Occurs mainly in the liver Glycolysis Gluconeogenesis Glucose Glycogenesis Glycogenolysis Carbohydrate Metabolism 13  Also related:  Lipogenesis – the conversion of carbohydrates to fatty acids   Fat is another energy storage form, but not as quickly accessible as glycogen Lipolysis – the decomposition of fat  The sum or net of all of these processes determines the level of blood glucose. Regulation of Plasma Glucose 14  Organs / systems involved in glucose regulation  Liver :  Muscle  Glucose Glycogen Glucose Skeletal & heart  Pancreas  Synthesizes hormones Insulin and Glucagon, somatostatin  Other Endocrine glands    Anterior pituitary gland ( growth hormone) Adrenal gland (epinephrine and cortisol) Thyroid gland (thyroxine) Regulation of Plasma Glucose 15  If plasma glucose is decreased :  Glycogenolysis   The liver releases glucose into the plasma (quick response) Gluconeogenesis and lipolysis  If plasma glucose is increased :  Glycogenesis   Liver stores glucose as glycogen Lipogenesis  Formation of lipids Hormones that Regulate Glucose 16  Insulin  Most important & only one to decrease glucose level  Synthesized in the Beta cells of the Islets of Langerhans (in the pancreas)  Released when plasma glucose is increased Action / Effects of insulin  Facilitates glucose entry into cells  cell membranes need insulin to be present for glucose to enter  Promotes liver glycogenesis  glucose to glycogen  Promotes glycolysis  speeds up utilization of glucose in cells  Promotes synthesis of lipids from glucose  Such as the formation of Triglycerides  Promotes amino acid synthesis from glucose intermediates  Decreases / inhibits glycogenolysis and gluconeogenesis Insulin Control 18 Insulin secretion controlled by:   Blood glucose level Certain Amino Acids ie. leucine, & arginine Counterregulatory Hormones 19  Glucagon  2nd most important glucose regulatory hormone  Referred to as a hyperglycemic agent  Synthesized in alpha cells of the islets of Langerhans Action/Effect of Glucagon 20  Stimuli – decreased plasma glucose  Action  Increases glycogenolysis & gluconeogenesis  Promotes breakdown of fatty acids  Promotes breakdown of proteins to form amino acids  Increases plasma glucose concentration Other Regulatory Hormones 21  Epinephrine  One of two glucose regulating hormones from the adrenal gland  Origin – adrenal medulla  Action/effect  Inhibits insulin secretion & release  Promotes lipolysis  Stimulates glycogenolysis  Immediate release of glucose  Stimuli  Neurogenic - based on physical / emotional stress.  Adrenal tumors Other Regulatory Hormones 22  Glucocorticoids - such as cortisol  Origin – adrenal cortex  Effect – antagonistic to insulin increases blood glucose  promotes gluconeogenesis from breakdown of proteins  inhibits the entry of glucose into muscle cells   Stimuli – anterior pituitary’s ACTH Other Regulatory Hormones 23  Growth Hormone (GH) and Adrenocorticotropic Hormone (ACTH)   Origin – anterior pituitary gland Effect – antagonistic to insulin   Increases plasma glucose levels  inhibits insulin secretion  inhibits entry of glucose into muscle cells  inhibits glycolysis  inhibits formation of triglycerides from glucose Stimuli decreased glucose stimulates its release  increased glucose inhibits its release  Other Regulatory Hormones 24  Thyroid hormones (such as thyroxine)  Origin – thyroid gland  Effect increases absorption of glucose from intestines  Promotes comversion of liver glycogen to glucose   Stimuli – pituitary gland’s TSH Other Regulatory Hormones  Somatostatin  Origin-Delta cells of the islets of Langerhans in the pancreas  Effect - increase plasma glucose  Actions antagonistic to insulin,  inhibits endocrine hormones including glucagon & growth hormone  References  Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins.  Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson . 26