1. Carbohydrates Part 1

2. M. Zaharna Clin. Chem. 2009 Introduction Organisms rely on the oxidation of complex organic compounds to obtain energy Three general types of such compounds are: Carbohydrates (CHO) Amino acids And lipids CHO are the primary source of energy for brain, erythrocytes and retinal cells Stored primarily as liver & muscle glycogen

3. M. Zaharna Clin. Chem. 2009 Carbohydrates: CHO Compounds containing C, H, O General formula (CH 2 O)n All CHO contain C=O and –OH functional groups There are some derivatives of this formula, carbohydrate derivatives can be formed addition of other chemical groups (phosphates, amines…) Classification of CHO is based on four different properties: 1. The size of the base carbon chain 2. The location of the CO functional group 3. The number of sugar units 4. The stereochemistry of the compound

4. M. Zaharna Clin. Chem. 2009 1- The size of the base carbon chain Can be classified based on the number of carbons in the molecule Trioses ( 3 Carbons) Tetroses Pentoses And hexoses The smallest CHO is glyceraldehyde (3 Carbon)

5. M. Zaharna Clin. Chem. 2009 2.The location of the CO functional group CHO are Hydrates of aldehyde or ketone derivatives based on the location of the CO functional group Aldose form – aldehyde as functional group Ketose form – ketone as functional group

6. M. Zaharna Clin. Chem. 2009 3- The number of sugar units Classification based on the number of sugar units in the chain 1. Monosaccharide 2. Disaccharide (2 sugars linked together) 3. Oligosaccharide (2 – 10 linked sugars) 4. Polysaccharide (Long sugar chains)

7. M. Zaharna Clin. Chem. 2009 Monosaccharides Simplest sugars; cannot be broken down into any simpler sugar 3 carbons = triose, 4 carbons = tetraose, 5 carbons = pentose, & 6 carbons = hexose Important pentose (5 carbon) sugars include ribose and 2-deoxyribose

8. M. Zaharna Clin. Chem. 2009 Disaccharides Formed from two monosaccharide with the production of water. Most common form is sucrose (table sugar), which is glucose and fructose Other forms include: Lactose (glucose and galatose) and maltose (glucose and glucose)

9. M. Zaharna Clin. Chem. 2009 Common Disaccharides Glucose + Fructose Glucose + Galactose Glucose + Glucose Sucrose ( table sugar )

10. M. Zaharna Clin. Chem. 2009 Polysaccharides Plants (cellulose); not digested by humans. Starch: principle CHO (polysaccharide) storage product of plants Glycogen: principle CHO storage product in animal. Formed by the combination of monosaccharide.

11. M. Zaharna Clin. Chem. 2009 4- Stereochemistry Mirror image forms D = right side OH, L = left side OH D & L designations are based on the configuration about the single asymmetric C

12. M. Zaharna Clin. Chem. 2009 Glucose Metabolism Glucose is a primary source of energy. Various tissues and muscles throughout the body depend on glucose from the surrounding extracellular fluid for energy. Nervous tissue cannot concentrate or store CHO, critical to maintain steady supply If glucose levels fall below certain levels the nervous tissue lose its primary energy source and is incapable of maintaining normal function.

13. M. Zaharna Clin. Chem. 2009 Fate of glucose CHO is digested (starch and glycogen). Amylase digest the nonabsorbable forms of CHO to dextrin and disaccharide which are hydrolyzed to monosaccharide. Maltase is an enzyme released by intestinal mucosa that hydrolze maltose to two glucose units Sucrase hydrolyze sucrose to glucose & fructose Lactase: hydrolyze lactose to glucose & galatose.

14. M. Zaharna Clin. Chem. 2009 Fate of glucose Disaccharides are converted into monosaccharide – absorbed by the gut transported to the liver by the hepatic portal venous blood supply. Glucose is the only CHO to be directly used for energy or stored as glycogen. Others (galactose & fructose) have to be converted to glucose before they can be used

15. M. Zaharna Clin. Chem. 2009 Lactose intolerance: due to a deficiency of lactase enzyme on or in the intestinal lumens, which is needed to metabolize lactose. Results in an accumulation of lactose in the intestine as waste lactic acid- causing the stomach upset and discomfort. Lactose intolerance

16. M. Zaharna Clin. Chem. 2009 After glucose enters the cell it can go into one of three metabolic pathways based on availability of substrate and nutritional status of cell. Ultimate goal is to convert glucose to CO 2 and H 2 O. During this process the cell obtains the high- energy molecule (ATP) from (ADP). Fate of glucose

17. M. Zaharna Clin. Chem. 2009 1 st step in all pathways Glucose is converted to glucose -6 phosphate using ATP- catalyzed by hexokinase. Glucose-6- phosphate enters the pathways: 1. Embden-Meyerhof pathway 2. Hexose Monophosphate shunt 3. Glucogenesis (storage of glucose as glycogen ) Glucose metabolism

18. M. Zaharna Clin. Chem. 2009 Glucose metabolism 1. Embden-Meyerhof pathway Glucose is broken down into two, three-carbon molecules of pyruvic acid that can enter the tricarboxylic acid cycle (TCA cycle) on conversion to acetyl-coenzyme A (acetyl-CoA). 2. Hexose Monophosphate shunt The principal functions of the pathway are the production of: o Deoxyribose and ribose sugars for nucleic-acid synthesis; o The generation of reducing power in the form of NADPH for fatty-acid and/or steroid synthesis;

19. M. Zaharna Clin. Chem. 2009 Major energy pathways involved either directly or indirectly with glucose metabolism 1. Glycolysis Breakdown of glucose for energy production 2. Glycogenesis 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 3. Glycogenolysis Breakdown of glycogen into glucose Glycogenolysis occurs when plasma glucose is decreased Occurs quickly if additional glucose is needed Pathways in glucose metabolism

20. M. Zaharna Clin. Chem. 2009 4. Gluconeogenesis Conversion of non-carbohydrate carbon substrates to glucose Gluconeogenesis takes place mainly in the liver 5. Lipogenesis Conversion of carbohydrates into fatty acids Fat is another energy storage form, but not as quickly accessible as glycogen 6. Lipolysis Decomposition of fat Pathways in glucose metabolism

21. M. Zaharna Clin. Chem. 2009 Regulation of Carbohydrate Metabolism The liver, pancreas, and other endocrine glands are all involved in controlling the blood glucose concentrations within a narrow range During a brief fast, glucose is supplied to the ECF from the liver through glycogenolysis. When the fasting period is longer than 1 day, glucose is synthesized from other sources through gluconeogenesis. Control of blood glucose is under two major hormones: insulin and glucagon, both produced by the pancreas

22. M. Zaharna Clin. Chem. 2009 Regulation of Carbohydrate Metabolism Other hormones also exert some control over blood glucose concentrations As needed hormones regulate release of glucose. Hormones work together to meet 3 requirements: 1. Steady supply of glucose. 2. Store excess glucose 3. Use stored glucose as needed

23. M. Zaharna Clin. Chem. 2009 Insulin Primary hormone responsible for the entry of glucose into the cell. Synthesized in the beta cells of islets of langerhans in the pancreas. Insulin release cause increase movement of glucose into the cells and increase glucose metabolism Is the only hormone that decreases glucose levels and is referred as a hypoglycemic agent.

24. M. Zaharna Clin. Chem. 2009 Glucagon Peptide hormone that is synthesized by the alpha cells of the islets cells of the pancreas Released during stress and fasting states. Released in response to decreased body glucose. Main function is to: increase hepatic glycogenolysis, and increase gluconeogenesis. Hyperglycemic agent

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26. Action of Hormones

27. M. Zaharna Clin. Chem. 2009 Epinephrine (adrenaline) Hormone produced by the adrenal gland Increases plasma glucose by: inhibiting insulin secretion, increasing glycogenolysis and promotes lipolysis. Release during times of stress

28. M. Zaharna Clin. Chem. 2009 Glucocorticoids Primarily Cortisol is released when stimulated by adrenocorticotropic hormone (ACTH). Cortisol increases plasma glucose by: Increasing gluconeogenesis, Inhibition of glucose uptake in muscle and adipose tissue and lipolysis. Insulin antagonist

29. M. Zaharna Clin. Chem. 2009 Thyroxine The thyroid gland releases thyroxine. Increases glucose levels by: increasing glycogenolysis, gluconeogenesis And intestinal absorption of glucose.

30. M. Zaharna Clin. Chem. 2009 Somatostatin Produced by the delta cells of the lslets of langerhans of the pancreas. The inhibition of insulin, glycagon Therefore only minor overall effect

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32. Hyperglycemia Increase in plasma glucose levels In healthy persons during a hyperglycemia state, insulin is secreted by the beta cells of the pancreatic islets of langerhans. Insulin enhances membrane permeability to cells in the liver, muscle, and adipose tissue. Hyperglycemia is caused by an imbalance of hormones.

33. M. Zaharna Clin. Chem. 2009 Diabetes Mellitus Metabolic diseases characterized by hyperglycemia resulting from defect in insulin secretion, insulin action or both. Two major types: (in 1979) Type I, (insulin dependent) and Type 2, (non insulin dependent) 1995: further categories by WHO: Type 1 diabetes, type 2 diabetes, other specific types and gestational diabetes mellitus.

34. M. Zaharna Clin. Chem. 2009 Type 1 diabetes Due to cellular-mediated autoimmune destruction of the β cells of the pancreas, causing an absolute deficiency of insulin secretion Or idiopathic type 1 diabetes that has no known etiology Commonly occurs in children (juvenile diabetes) Constitutes only 10% to 20% of all cases of diabetes Genetics play a minimal role, can be due to exposure to environmental substances or viruses. Treatment: insulin

35. M. Zaharna Clin. Chem. 2009 Characteristics of T1DM Abrupt onset, Insulin dependence, and ketosis tendency. One or more of the following markers are found in 85% to 90% of individuals with fasting hyperglycemia: Islet cell autoantibodies, Insulin autoantibodies, Glutamic acid decarboxylase autoantibodies

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37. Type 2 diabetes mellitus Due to insulin resistance and relative insulin deficiency. Type 2 constitutes the majority of the diabetes cases Most patients in this type are obese or have an increased percentage of body fat distribution in the abdominal region often goes undiagnosed for many years and is associated with a strong genetic predisposition

38. M. Zaharna Clin. Chem. 2009 Characteristics of T2DM Adult onset of the disease Ketoacidosis seldom occurring. These patients are more likely to go into a hyperosmolar coma and are at an increased risk of developing macrovascular and microvascular complications.

39. M. Zaharna Clin. Chem. 2009 Other specific types Secondary conditions, genetic defect in beta cell function or insulin action, pancreatic disease, disease of endocrine origin, drug or chemical induced. Characteristics of the disease depends on the primary disorder.

40. M. Zaharna Clin. Chem. 2009 Gestational diabetes mellitus Glucose intolerance that is induced by pregnancy Caused by metabolic and hormonal changes related to the pregnancy. Glucose tolerance usually returns to normal after delivery. An increased risk for development of diabetes in later years