MLAB 2401: Clinical Chemistry Keri Brophy-Martinez

1. MLAB 2401: Clinical ChemistryKeri Brophy-Martinez Carbohydrate Overview

2. 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

3. 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

4. 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

5. 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

6. 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

7. Carbohydrate Breakdown

8. 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

9. Biochemical Pathways in Carbohydrate Breakdown • Embden-Meyerhoff pathway • Converts glucose to pyruvate/lactate • Primary energy source for humans • Hexosemonophosphate shunt • Oxidizes glucose to ribose and CO2 • Produces NADPH as an energy source • Glycogenesis • Converts glucose to glycogen

10. 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

11. 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

12. Glycolysis Glycogenolysis Gluconeogenesis Glucose Glycogenesis

13. 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.

14. 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)

15. 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

16. 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

17. 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

18. Insulin Control Insulin secretion controlled by: • Blood glucose level • Certain Amino Acids ie. leucine, & arginine

19. Counterregulatory Hormones • Glucagon • 2ndmost important glucose regulatory hormone • Referred to as a hyperglycemic agent • Synthesized in alpha cells of the islets of Langerhans

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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 .