Lecture 8

Carbohydrates

Carbohydrates
• Most abundant class of biological molecules on Earth • Originally produced through CO2 fixation during photosynthesis

Roles of Carbohydrates
• • • • Energy storage (glycogen, starch) Structural components (cellulose, chitin) Cellular recognition Carbohydrate derivatives include DNA, RNA, co-factors, glycoproteins, glycolipids.

Carbohydrates
• Monosaccharides (simple sugars) cannot be broken down into simpler sugars under mild conditions • Oligosaccharides = "a few" - usually 2 to 10 • Polysaccharides are polymers of the simple sugars

Monosacharides
(C•H2O)n where n ≥3 • Triose (3 C) • Tetrose (4 C) • Pentose (5 C) • Hexose (6 C) • Heptose (7 C) • Octose (8 C)

Monosaccharides
• Polyhydroxy ketones (ketoses) and aldehydes (aldoses) • Aldoses and ketoses contain aldehyde and ketone functions, respectively • Ketose named for “equivalent aldose” + “ul” inserted • Empirical formula = (CH2O)n
O C H HO H C* C* C* OH H OH HO H H CH2OH C C* C* O H OH

CH2OH D-ribose

CH2OH D-ribulose

Monosaccharides are chiral
• Aldoses with 3C or more and ketoses with 4C or more are chiral • The number of chiral carbons present in a ketose is always one less than the number found in the same length aldose • Number of possible steroisomers = 2n (n = the number of chiral carbons)

O C H HO H H C* C* C* C*

H CH2OH OH H OH OH HO H H C C* C* C* O H OH OH

CH2OH D-glucose

CH2OH D-fructose

Stereochemistry
Enantiomers
H C HO H HO HO C* C* C* C* H OH H H H HO H H O O C C* C* C* C* OH H OH OH HO HO H H H

Diastereomers
O C C* C* C* C* H H OH OH H HO HO H H O C C* C* C* C* OH H H OH H HO H H H O C C* C* C* C*

Epimers
H O C OH H OH OH HO HO H H C* C* C* C* H H OH OH H

CH2OH L-glucose

CH2OH D-glucose

CH2OH D-mannose

CH2OH D-galactose

CH2OH D-glucose

CH2OH D-mannose

•Enantiomers = mirror images •Pairs of isomers that have opposite configurations at one or more chiral centers but are NOT mirror images are diastereomers •Epimers = Two sugars that differ in configuration at only one chiral center

Cyclization of aldose and ketoses introduces additional chiral center
• Aldose sugars (glucose) can cyclize to form a cyclic hemiacetal
H O C H ALCOHOL H O R2 R1 ALDEHYDE H O H C* O R2 HEMIACETAL R1 NEW CHIRAL CARBON

• Ketose sugars (fructose) can cyclize to form a cyclic hemiketal
H O C R ALCOHOL H O R2 R1 KETONE H O R C* O R2 HEMIKETAL R1 NEW CHIRAL CARBON

Cyclization of aldose and ketoses

Haworth Projections
O C1 H HO H H C2 C3 C4 C5 OH H OH OH H

In D configuration -OH up = beta -OH down = alpha 6 5 4 3 2 1 Anomeric carbon (most oxidized)

CH2OH

For all non-anomeric carbons, -OH groups point down in Haworth projections if pointing right in Fischer projections

Monosaccharides can cyclize to form Pyranose / Furanose forms
α = 64% β = 36% α = 21.5% β = 58.5%

α = 13.5% β = 6.5%

Isomeric forms of fructose

Conformation of Monosaccharides

Pyranose sugars not planar molecules, prefer to be in either of the two chair conformations.

Derivatives of Monosaccharides

Sugar Phosphates

Metabolized as phosphate esters

Deoxy Sugers
Hydrogen atoms replaces -OH group on C-2. Important to structure of nucleic acids.

Amino Sugars
Amino group (NH-) substituted for -OH group in monosaccharide.
CH2OH OH OH H H O H H NH C CH3
ß-D-N-acetyl glucosamine

OH

O

Sugar alcohols
Replace carbonyl oxygen to form polyhydroxy alcohols Glyceraldehyde glycerol -ose  -itol. Ribose  ribitol

Sugar acids
Oxidation of carbonyl group generate aldonic acids while C-6 oxidation results in uronic acids. glucose  gluconate or glucuronate

D-gluconate cyclizes to D-glucono-δ-lactone

β-D-glucuronate

Ascorbic acid
Derived from D-glucuronate. • Esential cofactor for enzymesthat catalyze the hydroxylation of proline and lysine • Primates cannot do the conversion, so must be supplied in the diet.

Monosaccharide structures you need to know
• • • • • • Glucose Galactose Fructose Ribulose Glyceraldehyde Dihydroxyacetone

Carbohydrates
• Monosaccharides (simple sugars) cannot be broken down into simpler sugars under mild conditions • Oligosaccharides = "a few" - usually 2 to 10 • Polysaccharides are polymers of the simple sugars

Glycosides
• Glycoside: a carbohydrate in which the -OH of the anomeric carbon is replaced by -OR • those derived from furanoses are furanosides; those derived from pyranoses are pyranosides • Glycosidic bondthe bond from the anomeric carbon to the -OR group:

CH2OH O hemiacetal

CH2OH O OH OH OH OH

Glycosidic Linkage

OH OH OH Hydrolysis H 2O CH2OH O OH O OH OH acetal OH

alcohol

OH

H 2O Condensation CH2OH O OH

OH glycosidic linkage

CH2OH H OH OH H OH O H H O H

CH2OH O OH H OH

Disaccharides
maltose
CH2OH H H OH OH H O H H OH H O H OH CH2OH H OH O OH H

cellobiose

H

OH

(α-D-glucosyl-(1->4)-β-D-glucopyranose)
CH2OH H OH OH H OH O O H H

(β-D-glucosyl-(1->4)-β-D-glucopyranose)

lactose
CH2OH

CH2OH H OH O OH H H

sucrose

OH OH H H

O H H OH

O H OH

CH2OH O H OH H OH H CH2OH

(β-D-galactosyl-(1->4)-β-D-glucopyranose)

(α-D-glucosyl-(1->2)-β-D-fructofuranose)

Reducing and nonreducing sugars
• carbonyl group or anomeric carbon are the most oxidizable site in monosaccharides and most disaccharides, therefore they are reducing sugers (glucose, maltose, cellobiose, lactose) • Detected by the ability to reduce Cu2+ --> Cu+ with Benedict’s reagent (blue --> red-orange insoluble products ). • Non-reducing sugars have both anomeric carbons in a glycosidic bond (e.g. sucrose).

Aglycones
• Aglycones: an organic molecule, such as alcohol, amines or thiols, that forms a glycosidic linkage with the anomeric carbon of the sugar to form glycoside. The most common encountered glycosides other than oligosacharides are the nucleosides or called N-glycosides.

guanosine (β-D-ribofuranosylguanine) Adenosine