BiochemistrySixth Edition

Chapter 11:Carbohydrates

Copyright © 2007 by W. H. Freeman and Company

Berg • Tymoczko • Stryer

Carbohydrates

Carbohydrates are aldehyde or ketone compounds with multiple hydroxyl groups.

They make up most of the organic matter on Earth and play extensive roles in all forms of life

They serve as energy stores, fuels, & metabolic intermediates

Ribose & deoxyribose sugars form part of the structural framework of RNA & DNA

Polysaccharides are structural elements in the cell walls of bacteria and plants. Cellulose is the most abundant organic compound in the biosphere.

Carbohydrates are linked to many proteins and lipidskey role in mediating interactions among cells and with other elements

Monosaccharides

Simplest carbohydrates Aldehydes or ketones with two or more hydroxyl groups Empirical formula, (C-H2O)n, literally a “carbon hydrate” Important fuel molecules as well as building blocks for nucleic acid Smallest monosaccharides are trioses (n = 3)

2 stereoisomers of Glyceraldehyde• (D- & L-)• are enantiomers (mirror images of each

other)

Glyceraldehyde has 1 asymmetric C

Monosaccharides

Monosaccharides (simple sugar molecules) can be classified according to the number of carbon atoms in the chain. Those most commonly found in humans include the following:

– 3 carbons: trioses (e.g., glyceraldehyde)– 4 carbons: tetroses (e.g., erythrose)– 5 carbons: pentoses (e.g., ribose, ribulose, xylose, xylulose)– 6 carbons: hexoses (e.g., glucose, galactose, mannose, fructose)

Stereoisomers

Stereoisomers are isomeric molecules that have

Same molecular formula and sequence of bonded atoms (constitution)

But which differ only in the three-dimensional orientations of their atoms in space

Two typesEnantiomersDiastereomers

Enantiomers

Enantiomers are two stereoisomers that are related to each other by a reflection:– they are mirror images of each other– which are non-superimposable– Human hands are a macroscopic example of stereoisomerism

S enantiomer R enantiomer

Diastereomers

Diastereomers are stereoisomers – that are not enantiomers– they are distinct molecules with the same structural arrangement of atoms that

are • non-superimposible• Not mirror images of each other

– epimers are diastereomers that differ in configuration of only one stereogenic center

(2S,3S)-tartaric acid (2R,3R)-tartaric acid (2R,3S)-tartaric acid

1 2 3

1 and 2 are enantiomers since they are mirror images1and 3 are diastereomers2 and 3 are diastereomers (epimers)

Monosaccharides

Simple momosaccharides with more than 3 carbon atoms– have multiple asymmetric carbon atoms– exist as diastereomers– Symbol D and L designate the absolute configuration of the

asymmetric carbon farthest from the aldehyde or keto group.

D-AldosesAldehyde group

Distal asymmetric centerNumbering

Epimers at C2

Pentoses and Hexoses cyclize to form Furanose and Pyranose Rings

Sugars in solution exist predominantly as rings and not open chains Open chain forms cyclize into rings

– Aldehyde reacts with an alcohol to form hemiacetal– Ketone reacts with an alcohol to form a hemiketal

Cyclization of aldoses: pyranose For aldoses, eg glucose

– C-1 aldehyde in open chain reacts with the C-5 hydroxyl group to form an intramolecular hemiacetal

– Resulting six membered ring: pyranose because it resembles pyran

Cyclization of ketoses: furanose For ketoses, eg Fructose

– C-2 of keto group in open chain reacts with the C-5 hydroxyl group to form an intramolecular hemiketal

– Resulting five membered ring: furanose because it resembles furan

Haworth Projection• Carbon atoms not shown• Plane of ring is perpendicular to the plane of screen with heavy line towards you

Fructose ring structures

C5 to C2 bond

C6 to C2 bond

Nomenclature of cyclic hemiacetals and hemiketals

Additional asymmetric center in cyclic forms– In glucose, C-1 is the anomeric center– In fructose (furanose form), C-2 is the anomeric center

• α means OH gp attached to anomeric carbon is below the plane of the ring• β means OH gp attached to anomeric carbon is above the plane of the ring

C5, DC2,

Confirmation of rings

Pyranose and furanose rings are not planar Pyranose: chair and boat Furanose: puckered

Pyranose : Chair form favored: Steric ReasonsSubstituents on the ring carbon atom have 2 orientations

AxialEquatorial

Furanose: Puckered or envelope formC-2 endo

C-2 out of the plane on the same side as C-5C-3 endo

C-3 out of the plane on the same side as C-5

Reactions of Monosaccharides

React with alcohol and amines to form adducts D-glucose reacts with methanol to form

– methyl-α-D-glucopyranoside– methyl-β-D-glucopyranoside– Differ in configuration at anomeric C– New bond is called glycosidic bond (anomeric C and O of hydroxyl)

The anomeric carbon can be linked to the nitrogen atom of an amine to form an N-glycosidic bond

Reactions of Monosaccharides

Reducing vs. Non reducing Sugars

Reducing Sugars eg., glucose– React with Fehling’s solution– Free aldehyde group is oxidized

Non Reducing Sugars eg., methyl glucopyranoside– Do not react with Fehling’s solution– Not readily interconverted to a form with free aldehyde gp

Modified Monosaccharides

Oligosaccharides

Oligosaccharides are built by the linkage of 2 or more monosaccharides by O-glycosidic bonds.– Maltose

• Two D-glucose residues are joined by a glycosidic linkage between – the α-anomeric form of C-1 on one sugar and – the hydroxyl oxygen atom on the C-4 of the adjacent sugar.

Disaccharides

Two sugars joined by an O-glycosidic bond

Polysaccharides

Larger polymeric oligosaccharides Play vital roles in energy storage and in maintaining the structural

integrity of an organism. Homopolysaccharides : same monosaccharide

– Starch– Glycogen– Cellulose– Chitin

Heteropolysaccharides– Provide extracellular support– Bacterial cell wall– Cartilage and tendons

Polysaccharides: Glycogen

Glycogen is highly branched polymer of glucose residues Most of the glucose units are linked by α-1,4- glycosidic bonds Branches are formed by α-1,6- glycosidic bonds Branches present about once in 10 units

Polysaccharides: Starch

Two forms– Amylose

• Unbranched :α-1,4- glycosidic bonds– Amylopectin

• Branched; α-1,6- glycosidic bonds about every 30 units

Polysaccharides: Cellulose One of the most abundant organic compounds in the biosphere Plays structural role in plants Unbranched glucose polymer with β-1,4- glycosidic bonds Forms long straight chains

Mammals lack cellulases and therefore cannot digest wood or vegetable fibers

Polysaccharide structure

Structure is determined by the type of linkages– β-1,4-linkages

• Straight chains• Optimal for structural purposes

- α-1,4- linkages• Favor bent structure• Suitable for storage

Glycosaminoglycans:Anionic Polysaccharides Made of repeating disaccharide units

Glucosamine or Galactosamine

At least 1 of the sugars has a negatively charged carboxyl or sulfate group Forms proteoglycans with proteins

Lubricants Structural component Mediate adhesion and bind factors stimulating cell proliferation

Enzymes: Oligosaccharide assembly

Glycosyltrasferases: catalyze formation of glycosidic bonds

Specific enzymes required– Specific to the sugars being linked

Sugar to be added is in activated form– sugar nucleotide

Proceeds with retention or inversion of configuration at glycosidic carbon atom

Human ABO Blood groups

One type of blood group possess either of these structures A antigen B antigen O antigen

These structures have a common oligosaccharide foundation termed O present in O antigen A antigen has N-acetylgalactosamine addition (α-1,3- linkage to galactose moiety of O antigen) B antigen has galactose addition (α-1,3- linkage to galactose moiety of O antigen) Specific glycosyltransferases add the extra monosaccharide to the O antigen.

Glycoproteins

Carbohydrates covalently attached to proteins

Small percentage of carbohydrates Components of cell membranes

cell adhesion binding of sperm to egg

Carbs linked to proteins throughAspargine (N-linked)

Takes place in the lumen of ER and in Golgi complex

Serine or threonine (O-linked)Takes place exclusively in the golgi complex

Golgi complex as sorting center

Golgi complex has 2 roles• Carbohydrate units of glycoproteins are modified• Major sorting center of the cell

• Targets proteins to Lysosomes, Secretory vesicles, and Plasma membrane

Lectins: Specific carbohydrate-binding proteins

• Ubiquitous• Animals, plants and microorganisms

• Promote interactions between cells• In plants: can serve as potent insecticides• Binding specificities in plants is well characterized

Animal lectin

Animal cell lectins facilitate cell-cell contact

In animal cell C-type lectins, Ca2+ ion links a mannose residue to the lectin

Selectins

Lymphocytes adhering to the lining of a lymph node

C-type lectins Bind immune-system cells to the sites of injury

Influenza hemagglutinin

• Viruses infect by binding to particular • Structures• Receptors: carbohydrates

Example: Influenza virus

• Binds to sialic acid residueson target cell surface through hemagglutinin

• Once inside the cell, viral protein,neuraminidase, cleaves glycosidic bonds to sialic acid and frees the virus for infection.

• Neuraminidase is a promising target foranti-influenza agents.