Different Carbohydrates

1. Different Carbohydrates First year MBBS 2019 Lecture DISACHARIDES AND GLYCOSIDES Dr . Sadia Haroon( deprtment of biochemistry)

2. Anomeric Carbon Epimeric Carbons Penultimate Carbon Terminal Alcohol Carbon Straight Chain Structure of Typical Monosaccharide (Glucose)

3. BIOMEDICAL IMPORTANCE Glucose — most important carbohydrate Glucose can be converted into glycogen ribose galactose Glycoproteins — molecular targeting Antibodies and blood clotting factors Structural components of cell membranes

4. Neuronal adhesion in development of nervous system (protein-glycan-heparan-sulfate) Constituents of extra cellular matrix Diseases associated with carbohydrates Diabetes mellitus Galactosemia Lactose intolerance Glycogen storagediseases

5. General characteristics • The term carbohydrate is derived from the french: hydrate de carbone • compounds composed of C, H, and O • empirical formula: (CH2O)n

6. General characteristics • Most carbohydrates are found naturally in bound form rather than as simple sugars • Polysaccharides (starch, cellulose, inulin, gums) • Glycoproteins and proteoglycans (hormones, blood group substances, antibodies) • Glycolipids (cerebrosides, gangliosides) • Glycosides • Mucopolysaccharides (hyaluronic acid) • Nucleic acids

7. Classification of carbohydrates • Monosaccharides- glucose, fructose • Oligosaccharides • Di, tri, tetra, penta, up to 9 or 10 • Most important are the disaccharides-lactose, sucrose • Polysaccharides or glycans • Homopolysaccharides-starch, glycogen, cellulose • Heteropolysaccharides • Complex carbohydrates

8. DERIVED CARBOHYRATES Oxidation Reduction Amino Deoxy Products Products Sugars Sugars Gluconic acid Glycerol Glucosamine Glucuronic acid Ribitol Galactoseamine Glucaric acid Mannoseamine Deoxyribose “These are derived from carbohydrates by various chemical reactions”

9. Monosaccharides • also known as simple sugars • classified by • the number of carbons and • whether aldoses or ketoses • Examples-glucose (blood sugar), fructose(sweetest sugar) are principal monosaccharides in food

10. Two types of pyranose form Chair form Boat form

11. The carbonyl group - monosaccharides • The carbonyl group is “free” in the straight chain form • But not free in the ring form • BUT remember – the ring form and the straight chain form are interchangeable • So allmonosaccharides are reducing sugars • All monosaccharides reduce Benedict’s reagent

12. REDUCING SUGARS • All monosacchs are reducing sugars. • They can be oxidised by weak oxidising agent such as Benedict’s reagent • Benedict's reagent is a solution of copper sulfate, sodium hydroxide, and tartaric acid. Aqueous glucose is mixed with Benedict's reagent and heated. The reaction reduces the blue copper (II) ion to form a brick red precipitate of copper (I) oxide. Because of this, glucose is classified as a reducing sugar.

13. Benedict’s Test • Benedict’s reagent undergoes a complex colour change when it is reduced • The intensity of the colour change is proportional to the concentration of reducing sugar present • The colour change sequence is: • Blue… • green… • yellow… • orange… • brick red

14. Benedict͛s test • Qualitative and semi quantititaive test. • Interpretation: • Drawback– testisnotspecificforglucose • ObservationInference • NochangeincolourNosugarGreencolour0-0.5mg% + • Yellow0.5-1.0mg%++ • Orange1.0-1.5mg%+++ • Brickred1.5-2mg%++++

15. 2.5 IMPORTANT MONOSACCHARIDES • GLUCOSE • FRUCTOSE • GALACTOSE • D-Glucose: • D-glucose (dextrose) is the primary fuel in living cells especially in brain cells that have few or no mitochondria. • Cells such as eyeballs have limited oxygen supply and use large amount of glucose to generate energy • Dietary sources include plant starch, and the disaccharides lactose, maltose, and sucrose

16. DISORDERS ASSOCIATED WITH GLUCOSE • DIABETES MELLITUS • GLYCOSURIA RENAL SUGAR THRESHOLD IT IS THE MAXIMUM CAPACITY OF KIDNEYS TO REABSORB GLUCOSE.

17. BIOLOGICAL SIGNIFICANCE • BRAIN CELLS, RBCS AND THE GROWING EMBRYO ONLY UTILIZE GLUCOSE AS A SOURCE OF ENERGY. • ENERGY SOURCE FOR CELLS IN THE BODY. • BUILDING BLOCK OF DISACCHARIDES AND POLYSACHHARIDES • IT IS THE SUGAR PRESENT IN BLOOD. • NORMAL VALUES FASTING: 70 TO 99MG/DL RANDOM:BELOW 140 MG/DL

18. Normal blood glucose level (mg/dl) Fasting (6-12 h after meals) 70-110(126) 130-150 1 h after CHO meals 2 h after CHO meals 70-110(126) Starvation (prolonged fasting) 60-70

19. What is glucose homeostasis??? It is the maintenance of blood glucose level within the normal range

20. DIABETES (diabetes mellitus) • Characterized by high blood glucose levels that splills over into the urine • These high glucose levels impairs the insulin-stimulated glucose entry into cells and starve the cells of insulin. • This leads to ketosis or high levels of ketone bodies (acids) that hinders the buffering capacity of the blood in the kidney, which controls blood pH (by excreting excess H+ ions into the urine). • The H+ excretion is accompanied by the excretion ammonia, sodium,potassium, and phosphate ions causing severe dehydration • This leads to excessive thirst symptom of diabetes and life-threatening decrease in blood volume.

21. Major factors contributing to hyperglycemia observed in Type 2 diabetes. Progression of blood glucose and insulin levels in patients with Type 2 diabetes.

22. Typical progression of Type 2 diabetes.

23. Glycogenolysis (Liver glycogen) Gluconeogenesis (mainly from amino acids) Diet by digestion and absorption Main source during prolonged starvation (> 18 hrs) Source during early fasting (12- 18 hrs) mostly Blood glucose Uptake by Tissues as muscles, adipose tissue & brain Oxidation glycogenesis lipogenesis

24. Important monosaccharides. Cont.... • GALACTOSE • is necessary to synthesize a variety of biomolecules (lactose-in mammary glands, glycolipids, certain phospholipids, proteoglycans, and glycoproteins) • Galactose and glucose are epimers at carbon 4 and interconversion is catalysed by enzyme epimerase. • Medical problems – galactosemia (genetic disorder) where enzyme to metabolize galactose is missing; accumulation of galactose in the body can cause liver damage, cataracts, and severe mental retardation

25. Important monosaccharides. Cont • FRUCTOSE • D-fructose (levulose) is often referred as fruit sugar and is found in some vegetables and honey • This molecule is an important member of ketose member of sugars • It is twice as sweet as sucrose (per gram basis) and is used as sweeting agent in processed food products • It is present in large amounts in male reproductive tract and is synthesised in the seminal vesicles.

26. Disaccharides • Most common are the disaccharides • Sucrose, lactose, and maltose • Maltose ( 2 molecules of D-glucose) • Isomaltose • Lactose (a molecule of glucose and a molecule of galactose) • Sucrose (a molecule of glucose and a molecule of fructose)

27. Alfa & beta GLYCOCIDIC BOND

29. Maltose • 2-glucose molecules joined via a(1,4) linkage • known as malt sugar • produced by the partial hydrolysis of starch (either salivary amylase or pancreatic amylase) • a nutrient (malt extract) as a sweetener and as a fermentative reagent

30. Maltose =>

31. Isomaltose • 2Glucosein(16)linkage • Reducingdisaccharide • Producedduringpartialhydrolysisofstarchandglycogen

32. Lactose • b-D-galactose joined to a-D-glucose via b (1,4) linkage • Called Milk sugar • b-lactose is sweeter and more soluble than ordinary a- lactose

33. Lactose intolerance • Lactose (milk sugar) in infants is hydrolyzed by intestinal enzyme lactase to its component monosacch for absorption into the bloodstream (galactose epimerized to glucose). • Most adult mammals have low levels of beta-galactosidase. Hence, much of the lactose they ingest moves to the colon, where bacterial fermentation generates large quantities of CO2, H2 and irritating organic acids. • These products cause painful digestive upset known as lactose intoleranceand is common in the African and Asian decent.

34. Lactose =>

35. Sucrose • also known as table sugar • commercially obtained from sugar cane or sugar beet

36. Sucrose =>

37. Disaccharidesofimportance Sugar Composition Source ClinicalSignificance D-glucopyranosyl-(1-2)D-fructofuranoside Caneandbeetsugar,sorghumandsomefruitsandvegetables Raregeneticlackofsucraseleadstosucroseintolerance— diarrheaandflatulence Sucrose Lackoflactaseleadstolactoseintolerancediarrheaandflatulence;maybeexcretedintheurineinpregnancy D-galactopyranosyl-(1-4)D-glucopyranose Milk Lactose

38. Disaccharides • Whentwomonosaccharidesarecombinedtogetherbyglycosidiclinkage,adisaccharideisformed. • Twotypes:- Non-reducing SucroseTrehalose Canesugarinyeast Reducing LactoseMaltose MilksugarMaltsugar

39. OLIGOSACCHARIDE SUGARS • Oligosaccharides are small polymers often found attached to polypeptides in glycoproteins and some glycolipids. • They are attached to membrane and secretory proteins found in endoplasmic reticulum and Golgi complex of various cells • Two classes: N-linked and O-linked

40. GLYCOSIDES

41. Carbonyl Carbon of a Monosaccharide is attached, by an Acetal linkage, to an Alcoholic group of a second compound.(Acetal is an organic molecule where two separate oxygen atoms are single bonded to a central carbon atom) H- C=O  H-C-OH  OH-C-H  H-C-OH  H-C-OH  CH2OH Glycosides OH  CH3 Methyl Glucoside

42. Glycosides • Glycosides are compounds in which: • A Monosaccharide is attached to an Alcoholic group of a second compound By Glycosidic Linkage. • Glycosidic Linkage is Defined as an: • Acetal Linkage Between Carbonyl Carbon of a Monosaccharide and Hydoxyl Group of an Another Compound.

43. In Glycosides Other Compound May or May Not be a Monosaccharide • When the alcoholic compound in a Glycoside is a Non-Carbohydrate it is called Aglycon. • In methyl Glucoside Methyl group is an Aglycon.

44. H- C------O  H-C-OH  OH-C-H  H-C-OH  H-C-OH  CH2OH CH3 Methyl Glucoside In methyl Glucoside Methyl group is an Aglycon Aglycon Glycon

45. Disaccharides are Glycosides in which both the Components are Monosaccharides,Such as Lactose (Glucose + Galactose)

46. Glycosides • Formed by a reaction between the anomeric carbon (in the form of hemiacetal or hemiketal) with alcohols or phenols. • Are named according to the reacting sugar. • Any glycosidic linkage is named according to the type of parent sugar egglucosidic, galactosidic or fructosidic linkages.

47. GLYCOSIDES A glycoside is an organic compound, usually of plant origin, that is composed of a sugar portion linked to a non-sugar moiety. The sugar portion is called glycone, while the non-sugar portion is called aglycone .

48. GLYCOSIDES The linkage between the sugar and the aglycone is an acetal linkage. Types of Glycosides : According to atoms involved in the glycosidic linkage: 1- O-glycosides 2- C-glycosides 3- S-glycosides 4- N-glycosides

49. Types of Glycosides • Monosaccharide units may condense in the form of di-, oligo- & polysaccharides where the second sugar reacts as an alcohol & condenses with the anomeric carbon by removal of H2O. • A sugar may also condense with a non-sugar radical (aglycon) • Nucleoside: (pentose sugar + nitrogenous base)

50. Types of Glycosides • Contraindicated in ventricular tachycardia. • Chemically, Digitonin 4Galactose +Xylose+digitogenin (aglycone) OUABAIN:It gains interest as class 1C antiarrhythmic drug that inhibit active transport of sodium in myocardium in vivo. It prevents paroxysmal atrial fibrillation.