Section 6: Carbohydrate Metabolism 1.

Carbohydrate chemistry

10/14/2005

Overview of catabolism
FATS POLYSACCHARIDES PROTEINS

Stage 1 fatty acids, glycerol glucose, other sugars

amino acids Stage 2

acetyl CoA
H2O O2

CoA v e CO2
Stage 3 Krebs cycle

oxidative phosphorylation ATP ADP + Pi

adapted from Fig. 14.12

Carbohydrates

aka saccharides (suffix: -ose) elements: C, H, O common empirical formula: (CH2O)n n 3 monosaccharides
aka simple sugars carbon chain unbranched 1 carbonyl (C=O) group at end of chain: aldehyde not at end: ketone 2 or more OH groups # OH groups = n 1

oligosaccharides/polysaccharides

contain a few/many linked monosaccharides

Monosaccharides: properties

very polar (hydrophilic)

functional groups OH: H-bond donor & acceptor =O: H-bond acceptor

chemically reactive, especially the carbonyl group, which reacts with:

OH groups, forming rings oligosaccharides polysaccharides oxidants & reductants amino groups on proteins (glycation)

Stereoisomerism (chirality)

stereoisomers
differ only in arrangement of atoms or groups any C with 4 different groups attached (asymmetric or chiral C)

enantiomers: a pair of molecules that are nonsuperimposable mirror images of one another H2C OH example: trioses C O simplest monosaccharides H2C OH DHA: achiral (no stereoisomerism) dihydroxyacetone DHA (a ketose) GA: D & L forms O O H H in general, C C OH HO H H # possible stereoisomers C C n = 2 (n = # asymmetric Cs) H2C OH H2C OH D forms more common L-glyceraldehyde D-glyceraldehyde

rotating L & D forms

GA (an aldose)

Glucose

most important monosaccharide the major monosaccharide in most organisms main form in which carbohydrate transported in blood main roles: precursor of many biomolecules energy source (fuel) aka dextrose O H C H2C OH abbreviation: glc 1 H C OH C O 2 6 carbons: a hexose

carbon numbering starts at end nearest C=O

HO C H H C OH H C OH H2COH D-glucose (an aldohexose)

other hexoses: fructose (frc) galactose (gal) 5 mannose

3 4 5 6

HO C H H C OH H C OH H2COH D-fructose (a ketohexose)

Glucose: ring formation (cyclization)

carbonyl C is subject to nucleophilic attack by OH groups (arrow), forming a hemiacetal H2COH 2 isomers form: O H O
6 5 1

a: OH projects on side of ring opposite from C6 (trans to C6)

H C OH HO C H H C OH H C OH H2COH D-glucose
6
5 4 3

H2COH C OH H H H C OH H C HO C C O H OH

HO

H OH
3

H
1

H
2

OH

H a ring form

OH

b: OH projects on same side of ring as C6 (cis to C6)

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H2COH H HO H OH H O OH H H OH

open-chain form

b ring form

Glucose: ring structure

cyclic forms of monosaccharides are usually drawn as Haworth projections, even though rings not actually planar tetrahedral geometry H2COH H CH OH around each ring atom O H 2 H H O HO causes 2 atoms to be H H OH H H OH H O out-of-plane: HO OH OH H H OH chair conformation "chair" conformation a-D-glucopyranose of a-isomer 6-atom cyclic forms are Haworthprojections termed pyranoses after H2COH the heterocycle pyran
5 4 1 3 2

H HO

H OH

O OH H H

O pyran

H OH b-D-glucopyranose

the a&bisomers are called anomers; the former carbonyl C (C1 in this case) is called the anomeric C anomer formation: aka anomerization 6 anomeric C: H2COH only one that has 2 of its bonds to O O H H H O H the reactions are: OH H 1C OH H O rapid, reversible 2 H C OH H OH & dont need catalysts 3 a-D-glucopyranose HO C H forms in rapid-equilibrium 4 H C OH with each other H2COH 5 H C OH form % at equil. O OH 6
5 4 1 3 2

Glucose isomers

open-chain < 1 a 36 b 63

H2COH

open-chain form

HO

H OH H

H H OH

b-D-glucopyranose

Glucose: a & b ring forms

ball & stick representations of the a & b anomers galactose, an epimer of glc at C-4

a glc

4 1

b gal

b glc

Fructose isomers

like glc, fructose forms pyranoses it also forms 5-atom rings called furanoses furanoses are major forms in frc derivatives (e.g., sucrose) C2 is the anomeric carbon
1

OH OH HO C H H2C OH CH2 C C H C OH H H OH O C C H C OH HO H O H2COH D-fructose

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H2C OH C O

OH H2C O

OH 1CH2

C C H H HO OH C C HO H
a-D-fructofuranose

open-chain form

furan

Oxidation

carbohydrates with a free carbonyl group are easily oxidized, i.e., they are good reducing agents termed reducing saccharides/sugars O O oxidation reaction is O H C C used to measure [glc] H C OH H C OH in blood & other HO C H HO C H + 2 Cu+ fluids + 2 Cu2+ H C OH H C OH glc oxidase more H C OH H C OH reliable than Cu2+ H2COH H2COH color development D-glucose D-gluconate proportional to gluconate + H2O2 glucose + O2 glucose [H2O2]
oxidase

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Glycation of protein amino groups

carbonyl groups react slowly & reversibly with amines, e.g., protein side chains (abbreviation: Pr-NH2) the resulting aldimine rearranges very slowly & irreversibly to a ketimine function of long-lived proteins can be impaired probable factor H O Pr N Pr N H H in long-term C C CH2 damage caused H C OH H C OH C O by high blood HO C H HO C H HO C H Pr NH2 [glc] in diabetes H C OH H C OH H C OH mellitus
H C OH H C OH H C OH H2COH ketimine H2COH glucose H2COH aldimine adduct

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Next: 2. Glycosides & Polysaccharides