Chemistry of Carbohydrates- Part I Definition, classification and isomerism

Chemistry of Carbohydrates- Part I Definition, classification and isomerism

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  Chemistry of Carbohydrates-I Prof DrViyatprajna Acharya, MD, PhD Biochemistry
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  Learning objectives • Introductionto biomolecules • Why carbohydrates in medical science? • Classification of carbohydrates/Nomenclature • Isomerism in carbohydrates • Reactions of monosaccharides • Disaccharides • Polysaccharides • Other biochemically important carbohydrates
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  Introduction to Biomolecules •A biomolecule is any organic molecule synthesized by living organisms that participates in or is essential for biological processes. • Produced by or in living organisms • Mainly organic (C, H, O, N, etc.) • Occurs naturally in cells or tissues • Participates in biochemical pathways • Biomolecules often show specific 3D structures, optical activity, and chirality — features that determine their biological function • Carbohydrates, Protein, lipids, Nucleic acids, vitamins- Biomolecules • Most abundant biomolecule on Earth is carbohydrate, specifically cellulose- accounts for about half of the total organic carbon in the biosphere. •
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  WHY CARBOHYDRATES??? Main sourceof energy; Brain and RBC almost wholly dependent on them 4 Kcal / g Storage of energy – starch & glycogen Excess carbohydrate Fat
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  Glycoproteins and glycolipids– cell membrane Structural function- cell wall, ground substances for higher organisms, exoskeleton Dietary fibers In DNA & RNA Detoxification – Glucuronic acid
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  Why carbohydrates inmedical science??
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  Many diseases- relatedto carbohydrate molecules or its metabolism • Obesity • DM • Glycogen storage disprders • Mucopolysaccharidoses, other metabolic disorders • Lactose intolerance • PEM-Protein energy malnutrition
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  Biomedical application ofcarbohydrate molecules Fructose- Parenteral nutrition TPN-Dextrose Mannose-prevents UTI Sucrose & Galactitol- sweeteners in syrup Mannitol- Reduces edema Dextran- plasma expander GAGs- maximum medical applications Supplements for bone health Glycolipids- cell recognition and as vaccine adjuvants or diagnostic markers. Blood grouping ELISA Lectins- Glycomics research
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  Diagnostics • Glucose, HbA1c,GTT • Galactose tolerance test • Fructose- seminal fluid • D-xylose absorption test- malabsorption syndrome • Electrophoresis • ELISA • Inulin clearance test • Maltose- culture media • Agar-agar- culture media
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  www.drvpacharya.com
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  Carbohydrates= Hydrates ofcarbon • As the name implies, consist of carbon, hydrogen, and oxygen. • Hydrate=(water) hydrogen and oxygen. • The basic formula for carbohydrates is CH2O, meaning that there is one carbon atom, two hydrogen atoms, and one oxygen atom as the ratio in the structure of carbohydrates
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  DEFINITION Carbohydrates are polyhydroxy aldehydesor ketones or compounds which yield these on their hydrolysis.
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  Researchers who broughtthe molecule to present form • Andreas Marggraf (1747)- isolated sucrose from beet • Emil Fischer- Elucidated the structure of glucose, fructose, and other sugars; introduced Fischer projection. • Claude Bernard- Discovered glycogen and its role in liver metabolism. • Eduard Buchner- cell-free fermentation of sugars using yeast extract. • Louis Pasteur (1822–1895)- Studied fermentation of sugars by microorganisms.
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  • Walter Haworth-Determined cyclic structures of glucose and other carbohydrates; synthesized vitamin C (ascorbic acid). • Phoebus Levene- Identified ribose and deoxyribose sugars in nucleic acids. • Earl W. Sutherland- Discovered cyclic AMP (cAMP) derived from adenosine (a carbohydrate-based nucleotide). • Rosalind Kornfeld & Stuart Kornfeld- glycoprotein biosynthesis and N-linked oligosaccharides. • Luis Leloir- sugar nucleotides and pathways of galactose metabolism (Leloir pathway). • Gerty and Carl Cori- Cori cycle — conversion of lactate to glucose between muscle and liver. • Ten Feizi- carbohydrate microarrays for studying glycan–protein interactions. • Carolyn Bertozzi- bio-orthogonal chemistry — labeling glycans in living cells-- Revolutionized glycobiology and drug targeting. • Ajit Varki- Defines the field of modern glycomics.
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  Saccharides (Gr. Saccharon= sugar)/ Sharkara (Sanskrit) Classified based on number of sugar units: Monosaccharides (1) Disaccharides (2) Oligosaccharides (3-10) Polysaccharide (> 10)
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  Most of thenames of carbohydrates end in -ose • Glucose-What plants make • Maltose- used in making beer (disaccharide) • Fructose – found in fruit (monosaccharide) • Sucrose- Table sugar (disaccharide) • Lactose – In milk (disaccharide)
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  Monosaccharides • Simple sugars •Single polyhydroxy aldehyde or ketone derivative • Can’t be hydrolyzed any further • Most abundant monosaccharide in nature- D- Glucose • Building blocks of all carbohydrates
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  Monosaccharides are classifiedbased on position of carbonyl group and number of carbon atoms Position of carbonyl group At C1, carbonyl is an aldehyde: Aldose At any other carbon, carbonyl is a ketone: Ketose Number of carbons Three carbons: Triose Four carbons: Tetrose Five carbons: Pentose Six carbons: Hexose Seven carbons: Heptose
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  Monosaccharides Aldoses (e.g., glucose)have an aldehyde group at one end. Ketoses (e.g., fructose) have a keto group, usually at C2. C C O H H C H H O C O H H C O H H C H 2O H D -glucose O H C H HO C OH H C OH H CH2OH CH2OH C O D-fructose
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  Cn(H2O)n
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  Aldoses
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  Ketoses
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  Disaccharides •Maltose (Glucose +Glucose) •Lactose ( Glucose + Galactose) •Sucrose ( Glucose + Fructose)
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  Trisaccharides •Raffinose – Glucose+ Galactose + Fructose- legumes and seeds • Trehalose- Glucose +Glucose (α 1→1)- fungi, yeast, insects; protects against dehydration • Melezitose- Glucose + Fructose + Glucose- Found in honey and plant saps (from aphids) • Gentianose- Glucose + Fructose + Glucose- Found in gentian roots
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  Higher Oligosaccharides (Tetrasaccharide andabove) Stachyose- beans and soy Verbascose- legumes Fructo-oligosaccharides (FOS)- Prebiotics; promote gut flora growth Mannan-oligosaccharides (MOS)- Used in animal feed; bind pathogens in the gut Glycoprotein/Glycolipid Oligosaccharides- Found on cell membranes; function in cell recognition and signaling
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  Polysaccharides / Glycans Poly= Many Glycans / Complex carbohydrates Linear (Cellulose)or branched (Glycogen) High MW Sparingly soluble in cold water Form colloidal solution on heating Not sweetish 2 types
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  Polysaccharides Homopolysaccharides Heteropolysaccharides Same typeof sugar units • Starch • Glycogen • Dextrin • Inulin • Cellulose Different types of sugar units A. Agar & Agarose B. Mucopolysaccharides/GAGs • Heparin • Chondroitin sulfate • Hyaluronic acid • Dermatan sulfate • Keratan sulfate • Blood group polysaccharides
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  Structural arrangement ofmonosaccharide •Empirical formula- doesn’t give any idea about the arrangement e.g. Glucose- C6H12O6 •Straight chain structural formula (Fischer projection) •Cyclic formula ( Haworth projection) •Boat and chair form (X-ray diffraction)
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  Fischer projection- Linear •Used for monosaccharides (especially aldoses and ketoses) in their linear form. • The most oxidized carbon (aldehyde or ketone) is placed at the top. • Horizontal lines represent bonds coming out of the plane. • Vertical lines represent bonds behind the plane. • Defines D & L configuration • Example – D-Glucose
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  Cyclic / Haworthprojection • Monosaccharides are in cyclic form in solution • The aldehyde (-CHO) or keto (-C=O) group react with a hydroxy group of the same molecule forming a bond hemiacetal or hemiketal respectively • Pyranose (6C) & Furanose (5C) • C1 with C-5 is condensed • Example – α-D-Glucopyranose
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  Boat and chairform • By X-ray diffraction it was seen • Chair form thermodynamically more stable • Chair form predominates in solution
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  Structural properties ofcarbohydrates
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  Isomerism in monosaccharides A.Structural (Constitutional) isomerism • Functional group isomerism • Chain isomerism B. Stereoisomerism- same formula but differ in spatial configuration • Optical isomerism • Epimers • Anomers
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  Asymmetric carbon atom •4 different groups attached to a C atom • A sugar molecule may have one or more asymmetric C atom • The number of stereoisomers possible depends on the number of asymmetric C atoms • If ‘n’ is the number of asymmetric C atom, then the number of possible is 2n D- Glyceraldehyde
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  Reference carbon atom •Also known as reference chiral carbon or asymmetric carbon • carbon atom farthest from the carbonyl group (–CHO or >C=O) that is attached to four different groups • In a Fischer projection, • If the –OH group on the reference carbon is on the right → D-form • If the –OH group is on the left → L-form • Locate the farthest asymmetric C atom, see to which side is the –OH group
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  D & Lisomerism CHO ← C1 (carbonyl) | H–C–OH ← C2 | HO–C–H ← C3 | H–C–OH ← C4 | H–C–OH ← C5 ← Reference carbon ⭐ | CH2OH D-Glucose CH2OH | C=O ← C2 (carbonyl) | HO–C–H | H–C–OH | H–C–OH ← C5 is reference carbon ⭐ | CH2OH D-Fructose
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  D & L- Glucose •Form mirror images • Penultimate C atom is the reference C atom for naming the mirror images • Absolute configuration • Stereoisomers Clinical significance- D sugars are naturally occurring and body metabolizes only D sugars
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  Optical isomers (Enantiomers)-d & l forms • When plane polarized light is passed through a solution of carbohydrates, it rotates the light either to the right or to the left • d (+)- right; dextrorotatory • l (-)- left; levorotatory • Presence of an asymmetric C atom will cause this optical activity • D and d are different • molecules that are mirror images of each other but non-superimposable. • Racemic mixture- equal conc. Of d &l form- zero optical activity
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  Clinical significance ofoptical isomers • Specific isomers have medicinal use whereas the other form may lead to side effects or may have less effectiveness • Naproxen- One isomer is tt of choice for arthritis and another leads to liver toxicity • Ethambutol- one isomer treats TB and another leads to blindness
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  Diastereoisomerism of glucose •For glucose around C2, 3 & 4- 8 isomers can be formed • Around C-5- 8 isomers • For C6H12O6- 16 different monosaccharides • But in human body only 3 are seen- Glucose, galactose and mannose • Glucose- Found in blood; Dextrose (D-Glucose) in clinical practice • Galactose- Milk sugar & glycoproteins; In liver gets epimerised to glucose • Mannose- Glycoproteins, plants; a prebiotic
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  Epimerism of aldoses •When sugars are different from one another only in configuration with regard to a single C atom, other than the reference C atom • Glucose and Mannose- at C2 • Glucose and Galactose- at C4
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  Anomerism of sugars-α & β forms • Anomerism is a special type of stereoisomerism seen in cyclic monosaccharides. It occurs due to the formation of a new chiral center (called the anomeric carbon) when the sugar’s open-chain form cyclizes into a ring. • When a monosaccharide (like glucose or fructose) forms a hemiacetal (aldose) or hemiketal (ketose) ring, the carbonyl carbon (C=O) becomes a new asymmetric carbon. • This carbon is called the anomeric carbon (C-1 in aldoses, C-2 in ketoses). • Depending on the position of the newly attached –OH group, two forms appear → α and β anomers.
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  Mutarotation • When afresh solution of crystallized D glucose is formed at RT, its specific rotation is +1120 , but after 12-18 hrs, it changes to +52.50 . • If initial crystallization is taking place at 980 c, then specific rotation is +18.70 and later changes to +52.70 . • ~1% is in glucofuranose form Form Percentage Specific rotation (°) α-D-glucopyranose ~36% +112 β-D-glucopyranose ~64% +18.7 Resulting mixture — +52.7°
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  Fructose- ketohexose • C2-anomeric C atom • 4 isomers • Aldose-ketose isomer of Glucose • Predominantly Furanose structure
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