CARBOHYDRATES:

STRUCTURE of CARBOHYDRATES

OVERVIEW
A. Carbohydrates
- most abundant organic molecules in nature
1. Forms
- polyhydroxylated ketones
- polyhydroxylated aldehydes
- compounds that can be hydrolyzed into the above compounds
2. Functions
- provides significant fraction of energy
- storage form of energy in the body
- as metabolic intermediates
- comprise large portions of nucleotides that form DNA and RNA
- cell membrane components that mediate some forms of intercellular communication
- role in lubrication
- role in immunity
- structural component of many organisms (bacterial cell wall, exoskeleton of many insects,
fibrous cellulose of plants)
3. Empiric Formula
- CnH2nOn  “hydrate of carbon”

CLASSIFICATION of CARBOHYDRATES
A. Monosaccharides
- simple sugars
- can be linked by glycosidic bonds  larger structures
B. Disaccharides
- contains two monosaccharides joined by an O-glycosidic bond

C. Oligosaccharides
- polymers containing 3-12 monosaccharide units
- often found attached through N- or O-glycosidic bonds to proteins to form glycoproteins
- ex: those found in glycoproteins
blood group antigens
D. Polysaccharides
- polymers composed of >10 monosaccharide units joined by glycosidic bonds to form linear chains or
branched structures
- ex: amylopectin (a form of starch)
cellulose
glycogen (storage form of glucose in human cells)
glycosaminoglycans
NOMENCLATURE of CARBOHYDRATES
A. Carbon Numbering System
- carbons are numbered sequentially
- aldehyde or ketone group is on the carbon with the lowest possible number

1. Pentoses of Clinical Significance

2. Hexoses of Clinical Significance

B. Reactive Groups
1. Aldose
- carbohydrates with an aldehyde (-CHO) as the most oxidized functional group
- carbohydrates that have free carbonyl group  suffix “-ose”
- ex: glucose is an aldohexose
- containing aldehyde group (aldo-)
- 6-carbon monosaccharide (-hexose)

2. Ketose
- ketone (C=O) group as the most oxidized functional group

- ketoses (with some exceptions like fructose)  suffix “-ulose”

STRUCTURE of MONOSACCHARIDES
A. Open-Chain (Acyclic) Forms
- <1% of each of the monosaccharides with 5 or more carbon units
1. Asymmetric Carbon
- all monosaccharides contain at least 1 asymmetric carbon
- ex: glucose
- carbons 2 - 5 are asymmetric  optically active enantiomers

a. Configuration
- trioses
- ex: glyceraldehyde
- simplest carbohydrates
- 2 optically active forms
b. Nomenclature
- for purposes of nomenclature  other sugars are considered to be derived from
glyceraldehyde
 i. D-sugar
- matches the configuration of D-glyceraldehyde around the asymmetric
carbon that is farthest from the aldehyde or ketone group
ii. L-sugar
- correspondingly matches L-glyceraldehyde

2. Isomers
- compounds that have similar chemical formula
- optical isomerism
- isomers that
- are alike with respect to what atoms are bonded together
- different in the way in which the atoms are oriented in space
- ex: C6H12O6
3. Epimers
- monosaccharides differ in configuration around 1 specific carbon atom (except of the
carbonyl carbon)
- also are isomers

4. Enantiomers
- special type of isomerism
- mirror images of each other
- rotate the same plane of polarized light to exactly the same extent but in the opposite directions
- identical physical properties except for the direction of rotation of plane-polarized light
- members are designated as D (vast majority in humans except L-fucose in glycoproteins and L-
iduronic acid in glycosaminoglycans) and L sugars
a. Dextrorotatory (D)
- plane of polarized light is rotated to the right (clockwise)
b. Levorotatory (L)
- plane of polarized light is rotated to the left (counterclockwise)
 5. Hemiacetals
- occur in
- linear form
- cyclic form
a. Intermolecular Hemiacetals
- unstable
- linear compounds
- occur when an alcohol reacts with an aldehyde

b. Cyclic Hemiacetals
- can be formed by similar intermolecular reactions
- glucose
- hydroxyl group at carbon 5 can react intermolecularly with the carbonyl
group at carbon 1  stable cyclic hemiacetal

B. Cyclic Forms
- occur much more frequently in solids and solutions than open-chain forms
- aldehyde or ketone groups have reacted with an alcohol group on the same sugar  hemiacetal or
hemiketal ring
1. Ring Structures
a. Pentoses (Ribose)
- 5 member ring (4 carbons, 1 oxygen)  furanose ring
b. Hexoses (Glucose)
- 6 member ring (5 carbons, 1 oxygen)  pyranose ring
2. Anomeric Carbon
- hemiacetal or hemiketal ring formation  creation of anomeric carbon at carbon 1 of aldose or
at carbon 2 of ketose  designated as  or  configuration (ex: -D-glucose and -D-
glucose which are anomers)
a.  Position
- hydroxyl on the anomeric carbon is below the plane of the ring
b.  Position
- hydroxyl on the anomeric carbon is above the plane of the ring
 - enzymes act preferentially to a certain configuration
- glycogen is synthesized from -D-glucopyranose
- cellulose is synthesized from -D-glucopyranose
- can form a covalent bond (glycosidic bond) with an alcohol  form an α or β glycoside
a. N-Glycosidic Bond
- links an anomeric carbon and a nitrogen atom, as in the covalent bond
between ribose and a purine or pyrimidine
3. Mutarotation
- results in characteristic changes in the optical rotation of a polarized light
- the cyclic  and  anomers of a sugar in a solution is in equilibrium (and readily be
interconverted)
- ex: solution of pure D-glucose
- 63% -pyranose
- 36% -pyranose
- interconversion process requires opening of the ring to the linear form
- occurs more rapidly in the presence of cellular mutarotases

4. Representation of Sugar Conformation

a. Fischer Conformation
- carbon chain is written vertically
- carbon 1 at the top
- hydroxyl and hydrogen substituents to the left or right
 b. Haworth Projection
- carbon 1 is drawn farthest to the right
- plane of the ring is “flat” on the paper
- -H, -OH, -CH2OH groups project above or below the plane

c. More Exact Representations of the 3-D conformation of sugars in nature

i. “Boat” Form
ii. “Chair” Forms
- x-ray diffraction analysis

REACTIONS INVOLVING MONOSACCHARIDES

A. Reducing Sugars
- if the oxygen in the anomeric carbon (carboxyl group) is not attached to any other structure (anomeric
carbons that have not formed glycosides)  reducing sugar  react with chemical reagents
(Benedict’s solution)  reduce the reactive component
- the anomeric carbon becomes oxidized in this process
- the free aldehyde of these sugars can reduce mild oxidizing agents
- the state of the oxygen on the anomeric carbon determines if the sugar is reducing or
nonreducing
- the other hydroxyl groups in the molecule are not involved
 identification of a nonreducing sugar represents evidence that the saccharide is a glycoside
1. Benedict’s Test
- one of the earliest tests for the presence of reducing sugar (glucose) in the urine of diabetics
- also positive for other reducing pentoses and hexoses
B. Oxidation-Reduction Reactions
1. Oxidation
- of -CH2OH group at carbon 6  -uronic acid (galactose  galacturonic acid)

- those compounds are major components of glycosaminoglycans

2. Reduction
- of the carbonyl carbon (aldehyde or keto group)  new alcohol group (polyols)
- ex: glucose  sorbitol (or glucitol)
fructose  sorbitol, Mannitol
galactose  galactitol
- of hydroxyl groups  deoxysugars (ribose  2-deoxyribose)  essential DNA components
C. Glycosidic Linkages
1. Acetals
- hemiacetals react with alcohols  acetals
2. Glycosides
- sugar react with alcohol  acetal (glycoside)

a. Classification
- sugar residue is glucose  glucoside
- sugar residue is fructose  fructoside
- sugar residue is galactose  galactoside
- when the side chain (R) is another sugar  glycoside is a disaccharide
- when the side chain (R) is a disaccharide  glycoside is a trisaccharide

b. Nomenclature
- glycosidic linkages are named by reading from left to right
- according to
- numbers of the connected carbons
- position of the anomeric hydroxyl group
- if the anomeric hydroxyl group is in the  configuration  -bond
- if in the  configuration  -bond
i. Lactose
- glycosidic bond between -galactose carbon 1 and carbon 4 of glucose 
(14) glycosidic bond
- the anomeric (or reducing) end of glucose residue is not involved in the
glycosidic linkage (and therefore lactose)  remains as a reducing
sugar

ii. Sucrose
- glycosidic bond between -glucose carbon 1 and -fructose carbon 2 
(1  2) glycosidic bond
- both reducing groups are involved in glycosidic linkage  not a reducing
sugar

iii. Maltose
- possesses an unattached anomeric carbon atom which have either or
configuration  reducing sugar
- glycosidic linkage is -1,4
 * are the anomeric carbon

3. Polysaccharides
- made up of monosaccharides covalently linked by glycosidic bonds
i. Homopolysaccharide
- contains one type of monosaccharide
ii. Heteropolysaccharide
- can contain diverse monosaccharides
- linear or branched
a. Starch
- mixture of amylose and amylopectin
- storage form of glucose in plants
i. Amylose
- linear unbranched polymer of -D-glucose units in a repeating sequence of
-1,4-glycosidic linkages

ii. Amylopectin
- branched polymer of -D-glucose with -1,4-glycosidic linkages and with
-1,6 branching points that occurs at intervals of approximately
25-30 -D-glucose residues
 b. Glycogen
- homopolysaccharide (contain only a single monosaccharide specie which is glucose)
- major storage form of carbohydrate in animals
- found most in
- liver
- muscle
- highly branched form of amylopectin
- -1,4 glycosidic linkages
- -1,6 branching points occurring every 8-10 D-glucose residues
c. Glycosaminoglycans
- heteropolysaccharides (contain a number of different monosaccharide species)
d. Cellulose
- chains of D-glucose units joined by -1,4-glycosidic linkages
- linear (unbranched)
- structural polysaccharides of plant cells
- not digested or hydrolyzed by human enzymes
4. Complex Carbohydrates
- carbohydrates can be attached by glycosidic bonds to noncarbohydrate compounds 
complex carbohydrates
- noncarbohydrate compounds
- purines and pyrimidines (nucleic acids)
- aromatic rings (steroids, bilirubins)
- proteins (glycoproteins, glycosaminoglycans)
- lipids (glycolipids)
- aglycone
- noncarbohydrate portion of the molecule
- glycoside
- generic name for the entire molecule
- glycosyl residue
- carbon 1 of aldose or carbon 2 of ketose participate in the glycosidic link
- if the sugar is glucose  glucosyl residue
a. O- and N-Glycosides
- hydroxyl group on the anomeric carbon of a monosaccharide can react with an -OH
or an -NH group of another compound to form a glycosidic bond
- if the group in the aglycone to which the sugar is attached is a
- -OH group  O-glycoside
- all sugar to sugar glycosidic bonds are O-type linkages
- -NH  N-glycoside
- typical aglycones
- purines, pyrimidines (sugar-nucleosides)
- aromatic rings (found in steroid and bilirubin)
- proteins (glycoproteins, glycosaminoglycans)
- lipids (glycolipids)
CARBOHYDRATE DERIVATIVES
A. Phosphoric Acid Esters of Monosaccharides
- formed from the reaction of phosphoric acid with a hydroxyl group of the sugar
1. Phosphorylation
- initial step in sugar metabolism
2. Phosphorylated Sugars
- metabolic intermediates
- ex: D-glucose 1-phosphate

B. Amino Sugars
- hydroxyl groups replaced by an amino or acetylamino group
1. Glucosamine
- product of chitin hydrolysis
- major polysaccharide of the shells of insects and crustaceans

2. Galactosamine
- in polysaccharide of cartilage, chondroitin sulfate
3. Acetylated Amino Sugars

a. N-Acetylglucosamine
b. N-Acetylneuraminic Acid
- important constituent of glycoproteins
- composed of an acetylated amino sugar, Nacetylmannosamine, covalently linked to
pyruvic acid
C. Sugar Acids
- produced by oxidation of the aldehydic carbon, the hydroxyl carbon, or both
1. Ascorbic Acid (Vitamin C)

2. Glucuronic Acid
- component of proteoglycans
- involved in bilirubin metabolism

D. Deoxy Sugars
- possess a hydrogen atom in place of 1 of their hydroxyl groups
- ex: 2-deoxyribose (DNA)

E. Sugar Alcohols
1. Structure
- monosaccharides (aldoses, ketoses)  reduced at the carbonyl carbon  polyhydroxy alcohols
(sugar alcohols)
a. Aldoses
- D-glucose  D-sorbitol
- D-mannose  D-mannitol
- D-galactose  dulcitol
 b. Ketoses
- form 2 alcohols because a new asymmetric carbon is formed in the process
- D-fructose  D-mannitol, D-sorbitol
2. Function
- intermediates in minor pathways

BLOOD GROUP ANTIGENS

- specific classes of oligosaccharides that may be bound to
- proteins
- lipids
- membrane surfaces
- >20 different blood groups containing >150 different antigens
A. Background
- transplant rejection and transfusion reactions
- self (like antigen) vs nonself (foreign antigen)
B. ABO Blood Group
- most commonly studied blood group
1. Structure
- ABO antigens are distinguished by a different single-sugar moiety on a common
oligosaccharide core
2. Blood Types
- Type O
- Type A
- Type B
- Type AB

R = protein or lipid molecule to which the oligosaccharide is bound

X = variable residue
- N-acetylglucosamine (blood type A)
- galactose (blood type B)
- no residue (blood type O)
SUMMARY