MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Carbohydrate Overview

Introduction 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 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 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 Mouth Salivary amylase Dextrins/ Maltose Stomach/Intestines Pancreatic amylase Monosaccharide Absorption into intestinal mucosa Delivered to liver

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 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 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 Glycogenolysis Gluconeogenesis Glucose Glycogenesis

Carbohydrate Metabolism 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 Organs / systems involved in glucose regulation Liver : Glucose Glycogen Glucose Muscle 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 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 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 Insulin secretion controlled by: Blood glucose level Certain Amino Acids ie. leucine, & arginine

Counterregulatory Hormones 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 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 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 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 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 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 .