MDSC1401 Chemistry of Carbohydrates Student PDF

16/09/2024 1 LEARNING OUTCOMES At the end of session the student should be able to CARBOHYDRATES Molecules of Functional Significance Describe the structure and clas...

16/09/2024 1 LEARNING OUTCOMES At the end of session the student should be able to CARBOHYDRATES Molecules of Functional Significance Describe the structure and classification of carbohydrates Explain how amylose differs from amylopectin Describe the carbohydrates of major significance to man and other animals Dr. Jerome Foster Department of Preclinical Sciences 1 2 1  16/09/2024 IMPORTANCE OF CARBOHYDRATES CHEMISTRY OF CARBOHYDRATES § Chief sources of energy - gives 4 cal/gram § Organic substances with C, H & O in the ratio of 1:2:1 (e.g. glucose - C6H12O6) § Storage forms of energy in man, animals & § Polyhydroxy-aldehyde or -ketone derivatives plants § Monosaccharides § Components of cell membranes & cell walls § simple sugars - cannot be hydrolysed further § Lubricate skeletal joints § further classified on the basis of number of carbon atoms and the presence of functional groups § Maintain structural integrity in tissues & organs § all have free reactive groups and are called reducing sugars § Used as drugs and raw materials 3 4 2  16/09/2024 CHEMISTRY OF CARBOHYDRATES Carbon Atoms Examples Functional Groups Trioses (3 carbon) Glyceraldehyde Aldehyde (aldotriose) Dihydroxy acetone Ketone (Ketotriose) § Disaccharides § two bound molecules of the same or different Tetroses (4 carbon) Erythrose Aldehyde (aldotetrose) monosaccharides § Can be reducing or non-reducing Pentoses (5 carbon) Ribose Aldehyde(Aldopentose) Xylose Aldehyde(Aldopentose) § reducing – free aldehyde or ketone groups which Xylulose Ketone (Ketopentose) can take part in reactions § nonreducing – lack these groups Hexoses (6 carbons) Glucose Aldehyde (Aldohexose) Galactose Aldehyde (Aldohexose) Fructose Ketone (Ketohexose) 5 6 3  16/09/2024 CHEMISTRY OF CARBOHYDRATES Examples Hydrolysis Products Sources Maltose glucose + glucose Malt § Oligosaccharides Lactose galactose + glucose Milk § contain 3 - 10 molecules of monosaccharide units § example - maltotriose (glucose + glucose + glucose) Sucrose glucose + fructose Sugar cane Isomaltose glucose + glucose Digestion of § Polysaccharides amylopectin § contain more than 10 molecules of monosaccharide units § can be homopolysaccharides or heteropolysaccharides 7 8 4  16/09/2024 SUGAR CONFORMATIONS CHEMISTRY OF CARBOHYDRATES Simplest way to represent a sugar is in its straight chain or Fischer projection (A) Examples of Homopolysaccharides Under normal physiological Examples Monosaccharide Unit Sources conditions in solution most forms of a sugar cyclize Starch Glucose potatoes, rice/cereals B is called Haworth projection Dextrin Glucose starch hydrolysis Glycogen Glucose liver, muscle Cellulose Glucose plant fibres C is called chair or Reeves projection Inulin Fructose leeks, chicory roots Chitin N-acetylglucosamine shells of arthropods Harpers Biochemistry 26 th edition 9 10 5  16/09/2024 SUGAR CONFORMATIONS Cyclization occurs through bonding of ISOMERISM OF CARBOHYDRATES active aldehyde or ketone group at C1 to an -OH Rings can be § Presence of anomeric carbon atoms causes pyranose – 5-membered (C1→C5) furanose – 4-membered (C1→C4) o Stereoisomerism – the 3-D orientation of molecules C1 is now an anomeric carbon – a centre of stereochemistry o Optical activity – ability to rotate plane-polarized light Harpers Biochemistry 26 th edition hemiacetal – ring formed from aldose sugar hemiketal – ring formed from ketose sugar 11 12 6  16/09/2024 ISOMERISM OF CARBOHYDRATES § Stereoisomerism – Straight Chains Based on rotation in glyceraldehyde mirror image the simplest triose with a chiral carbon chiral means 4 different groups attached D- and L- isomerism o –OH group of highest numbered chiral carbon is on the right (D) on the left (L) Harpers Biochemistry 26 th edition These isomers are called enantiomers 8 13 14 7  16/09/2024 ISOMERISM OF CARBOHYDRATES § Stereoisomerism – Ring structures § –OH orientation around anomeric carbon in mirror image cyclic/ring form below the ring’s plane is alpha (⍺) above the ring’s plane is beta (β) § these isomers are called anomers Harpers Biochemistry 26 th edition 15 16 8  16/09/2024 ISOMERISM OF CARBOHYDRATES ISOMERISM OF CARBOHYDRATES § Optical Activity § Stereoisomerism & Optical Activity are § direction of the rotation of plane-polarized light independent by sugars in solution § e.g. ⍺-D-(+)-glucose or β-D-(−)-glucose § dextrorotatory - (d) or (+) § Some sugars exist naturally in one form over the light is rotated to the right (clockwise) other § levorotatory - (l) or (−) § e.g. D-glucose or dextrose is the naturally light is rotated to the left (anticlockwise) found form Note: don’t confuse D- & L- enantiomers with § L-glucose is the enantiomer but not found dextrorotatory (d) and levorotatory (l) activity! naturally 17 18 9  16/09/2024 ISOMERISM OF CARBOHYDRATES § Epimers Glucose Isomerism § sugars have several chiral carbons glucose, galactose & § isomers of other carbons except anomeric mannose are aldohexoses carbon called epimers § E.g. epimers of glucose include fructose is a ketohexose § galactose (C4 epimer) § mannose (C2 epimer) 19 20 10  16/09/2024 POLYMERIZATION § Glycosidic bond linkage formed between OH group of anomeric carbon of one sugar with any OH group of another sugar (or alcohol) results in the loss of a water molecule (hydrolysis) involved in the formation of disaccharides and polysaccharides bond described by orientation of OH involved around anomeric carbon 21 22 11  16/09/2024 DISACCHARIDES Back to these… § Sugars containing 2 residues linked by glycosidic bond § Can be reducing or non-reducing § reducing – free aldehyde or ketone group at anomeric carbon which can take part in reactions § nonreducing – lack these groups at anomeric carbon 23 24 12  16/09/2024 Reduction Tests using Benedict’s Solution COMPLEX CARBOHYDRATES Benedict’s Solution - mixture of sodium carbonate, sodium citrate, & copper(II) sulfate pentahydrate Reducing sugars § Sugars strung into long complex chains i.e. free aldehyde or ketone group, e.g. glucose polysaccharides readily oxidised & act as reducing agents can reduce cupric ion (Cu2+) to cuprous ion (Cu+) § Starch give positive Benedict's reactions (blue to red-brown) § found in plants - used to store glucose § a mixture of two polysaccharides Nonreducing sugars o amylose (15-20%) no free anomeric OH group as all linked, e.g. sucrose o amylopectin (80-85%) no positive test with Benedict’s reaction positive test only when hydrolysed to glucose & fructose 25 26 13  16/09/2024 Differences between Amylose and Amylopectin: Amylose structure Criteria Amylose Amylopectin Starch constituent 15-20% 80-85% ⍺(1→4) helical coil from linear chain Structure Unbranched, linear Highly branched Molecular Wt. 60 kDa 500 kDa Linkage of glucose 250-300 residues joined by Residues joined by residues ⍺(1→4) bonds ⍺(1→4) (linear) and ⍺(1→6) bonds (branches) Amylopectin structure Digestion Harder to digest (tight coils) More easily hydrolysed ⍺(1→4) in linear portion Reaction with Iodine Blue-black colour (iodine Reddish-violet colour. ⍺(1→6) at branch points trapped in linear helical Branching means less globular structure). iodine trapped and lighter colour. Harpers Biochemistry 26 th edition 27 28 14  16/09/2024 COMPLEX CARBOHYDRATES COMPLEX CARBOHYDRATES § Cellulose § Inulin § β-D-glucose residues bound by β(1→4) § consists of a small number of β-D-fructose § digested by cellulase enzyme (absent in humans) residues § serves as dietary fibre and aids in peristalsis § joined by β(2→1) glycosidic linkages § used to measure the glomerular filtration § Dextrin rate, a test to assess the function of kidney § partially-hydrolysed products of starch 29 30 15  16/09/2024 COMPLEX CARBOHYDRATES COMPLEX CARBOHYDRATES § Glycogen § Heteropolysaccharides § polymer of ⍺-D-glucose units § polymer of different monopolysaccharides or derivatives § used to store glucose in liver and muscle § called animal starch & structurally similar to amylopectin § more branched than starch with 11 to 18 glucose § E.g. Mucopolysaccharides (MPS) residues between branch points § aka glycosaminoglycans (GAGs) § repeating units of amino sugar and acid sugars § found in extracellular matrix § Chitin § usually component of macromolecules called § polymer of esterified amino sugar N-acetyl-glucosamine proteoglycans (GAG/MPS + protein) § β(1→4) links between residues § act as tissue barriers, ground substance in joints, § found in exoskeleton of crustaceans & insects blood components, connective tissue components 31 32 16  16/09/2024 COMPLEX CARBOHYDRATES Chitin homopolysaccharide § Heteropolysaccharides derived sugar with amino & acid groups § polymer of different monopolysaccharides or derivatives § E.g. Mucopolysaccharides (MPS) Hyaluronic acid (a GAG) § GAGS include the following heteropolysaccharide § hyaluronic acid derived sugars with amino & acid § heparin groups § heparan sulphate § chondroitin sulphates ( 4- and 6-sulphates) § keratin sulphates (type I and II) adapted from Harpers Biochemistry 26 th edition 33 34 17  16/09/2024 Apple – The Healthy Fruit Pectins complex heteropolysaccharides found in plant cell walls § High carb content large part of dietary fibre 70% composed of galacturonic acid residues in ⍺(1→4) links o starch (amylose, amylopectin) other complex modified sugar residues present such as rhamnose, o cellulose (fibre) xylose, apiose they slow down sugar absorption during digestion § Actually has low glycemic index (doesn’t raise blood sugar) § Why with so much carbs? § answer is pectins 35 36 18  16/09/2024 Carbohydrates of biological importance § Sugar alcohols (Alditols) § their reduction form alcohols § Deoxy sugars § important constituent of DNA § Amino sugars § Important constituent of GAGS § Sugar acids § Important constituents of GAGS § Ascorbic acid (Vit C) § key vitamin 37 38 19  16/09/2024 Carbohydrates of Clinical Importance Carbohydrates of Clinical Importance § D-Sorbitol and D-Dulcitol when accumulated in large amounts cause strong osmotic effects Glycosides leads to swelling of cells Carbohydrate and a non-carbohydrate residue linked by a cataract, peripheral neuropathy and nephropathy glycosidic bond carbohydrate portion – glycone § D-Mannitol non-carb portion - aglycone useful in reducing intracranial tension by forced diuresis (excessive urination) Cardiac glycosides include digitalis, digitoxin & digoxin also used as a sweetener stimulates muscular contraction (cardiac stimulant) Streptomycin § Xylitol antibiotic used in treatment of tuberculosis used as a sweetener (sucrose substitute) doesn’t cause tooth decay 39 40 20  16/09/2024 Case Study Case Diagnosis Lactose Intolerance Presenting complaint A 30 year- man visits the physician with history of Cause: A deficiency of the brush border enzyme lactase abdominal cramps, diarrhea, and flatulence These symptoms appear about an hour after consuming If lactose is not cleaved, it cannot be absorbed and moves food & disappear when he avoid dairy products from small to large intestine Bacteria in large intestine can metabolize lactose, converting Laboratory investigation: Hydrogen breath test is positive it to acids and gas Diagnosis: lactose intolerance This causes abdominal discomfort and diarrhoea Advice: He was advised to avoid dairy products and to Large intestine environment also lacks oxygen take a tablet containing lactase in case he did eat any Hydrogen (H2) generated by bacterial fermentation is not product containing milk. oxidized but instead released, and in part is exhaled 41 42 21  16/09/2024 Case Diagnosis Lactose Intolerance FURTHER READING Cause: A deficiency of the brush border enzyme lactase Harpers Biochemistry 26th Ed. - pg 102-110 Increase in exhaled H2 upon ingestion of lactose can be used to diagnose the condition Treatment consists in omission of lactose in the diet Lactosuria: lactose found in the urine 43 44 22