Lecture 10 Carbohydrates

Carbohydrates

Aldehydes or ketones with at least two hydroxyl groups
-or substances that yield such compounds upon hydrolysis
-Empirical formula (CH2O)n
-Important components of key biomolecular structures (DNA, RNA, ATP, FAD)

Monosaccharides

the building blocks of carbohydrate polymers.
-The specific sugar, linking pattern, and branching determine its function.

Fischer projection formulas

Used to represent 3D sugar structures on paper
-Bonds drawn horizontally indicate bonds that project up and out of the plane of the paper
-Bonds drawn vertically project behind the plane of the paper.

Monosaccharide structure

A single sugar unit.

-Link together to form more complex carbohydrates

-Cannot be broken down into simpler sugars, thus they are the most basic unit of carbohydrates

-They exist in either a straight-chain or cyclic structure when dissolved in water

-They must contain a carbonyl group (aldehyde or ketone) and multiple hydroxyl groups

-Classified as either aldoses (if aldehyde) or ketoses (if ketone)

Energy

monosaccharides (especially glucose) are used as a primary energy source in cellular respiration

Building blocks

Link to make larger carbohydrates
-Starch, cellulose, glycogen, and part of DNA/RNA

Biological structures

These are commonly used to form cellular structures

Signaling and Recognition

Can be part of glycoproteins and glycolipids on cell surface
-Important in cell-to-cell communication and immune responses.

Aldose

carbonyl group is at an end of the carbon chain (in an aldehyde group)

Ketose

carbonyl group is at any other position (in a ketone group)

Trioses

three carbon backbone
-The simplest monosaccharides

Tetroses

four carbon backbone

Pentoses

five carbon backbone
-Components of DNA and RNA

Hexoses

six carbon backbone

Heptoses

seven carbon backbone

Stereoisomerism in sugars

In saccharides, many of the carbon atoms attached to hydroxyl groups are chiral centers.

-This is important because enzymes that act on sugars are stereospecific.

-Carbohydrates can have multiple chiral carbons.

-Stereochemistry determines interactions with other molecules

Biological carbohydrates

D conformation

Enantiomers

mirrored isomers
-Optically active
-Monosaccharides have >1 chiral carbons
-n chiral centers means 2^n stereoisomers

Reference carbon

the chiral center furthest from the carbonyl carbon

D isomers

OG on the reference carbon is on the right (dextro) in a projection formula
-In living organism
"LA to DC" (L amino acids and D carbohydrates are found in real life)

L isomers

OH on the reference carbon is on the left (levo) in a projection formula

sweet-taste receptors

TAS1R2 and TAS1R3
-Binding of a compatible molecule generates a "sweet" electrical signal to the brain
-Requires a specific steric match
-Artificial sweeteners match the receptor but are not metabolized like normal sugars

numbering carbons of a sugar

carbons are numbered beginning at the end of the chain near the carbonyl group
-This is not for reference carbons in identifying isomers

Epimers

Stereoisomers that have >1 chiral carbons, but only differ at 1

Monosaccharide cyclic structures

In aqueous solutions (in the body), aldotetroses and all monosaccharides (aldo or keto) with 5+ backbone carbon atoms cyclize
-A covalent bond forms between the carbonyl group and the oxygen of a hydroxyl group

Anomeric carbon

The aldehyde or ketone carbon in the open chain form
-Upon cyclization, they are a chiral carbon adjacent to the ring oxygen and the hydroxyl group

Anomers

Isomers whose only difference is at the anomeric carbon

What are the two stereoisomeric configurations produced by the cyclization of monosaccharides?

α and β

How can you distinguish between α and β forms in monosaccharides?

By looking at the orientation of the -OH group at the anomeric center relative to the -CH2OH group

α-form

the -OH group at the anomeric center is on the opposite side of the -CH2OH group

β-form

the -OH group at the anomeric center is on the same side of the -CH2OH group

Pyranoses

six-membered ring compounds

Furanoses

five-membered ring compounds

Haworth perspective formulas

a more accurate representation of cyclic sugar structure than Fischer projections
-Six-membered ring is tilted
-Bonds closest to the reader are drawn thicker than those father away

polysaccharides 3D structure

assume 3D structure with the lowest-energy conformation
-Determined by covalent bonds, hydrogen bonds, charge interactions, and steric factors
-Starch-> helical structure stabilized by internal hydrogen bonds
-Cellulose->extended structure with hydrogen bonds

Pyranose rings

tend to assume either of two "chair" conformations
-Interconvertible without breaking covalent bonds
-Transition requires energy input

O-glycosidic bond

covalent linkage joining two monosaccharides
-The Hydroxyl group of one sugar molecule reacts with the anomeric carbon of the other

Glycosidic bonds

covalent ether (R-O-R') bonds joining a carbohydrate molecule to another group
-May or may not be another carbohydrate
-two forms: α and β

α glycosidic bonds

hydroxyl groups are opposite of CH2OH groups

β glycosidic bonds

hydroxyl groups are on the same side of CH2OH groups

Monosaccharides

"simple sugars"
-Polyhydroxy aldehyde or polyhydroxy ketone unit

Glucose

monosaccharide

Fructose

monosaccharide

Galactose

monosaccharide

Deoxyribose

monosaccharide

ribose

monosaccharide

Oligosaccharides

Short chains of monosaccharide units/residues joined by glycosidic bonds (a bond that binds a sugar to another molecule)

Disaccharides

oligosaccharides with two monosaccharide units

maltose

disaccharide
glucose and glucose

lactose

disaccharide
galactose and glucose

sucrose

disaccharide
glucose and fructose

Reducing end

the end of a disaccharide or polysaccharide chain with a free (unattached) anomeric carbon

Reducing surgars

-are reducing agents
-they react with other molecules and donate electrons
-contain hemiacetal groups
-Used in some blood sugar testing
e.g., Lactose

Nonreducing sugar

e.g., Sucrose
-No free hemiacetal
-Can still form glycosidic bonds, just not donate electrons

Polysaccharides

sugar polymers with 10+ monosaccharide units

-ex: cellulose (linear), glycogen (branched)

-Most carbohydrates in nature

-Also known as "glycans"

Starch

Made of two glucose polymers, amylose and amylopectin.

10%-30% amylose (D-glucose units joined by the α-1,4-glycosidic linkages) and 70%-90% amylopectin (D-glucose with α-1,4-glycosidic bonds but with occasional α-1,6-glycosidic bonds)

-Over 50% of our dietary carbs

Polysaccharide conformations

assume the lowest energy conformations
-Structures are determined by covalent bonds, hydrogen bonds, charge interactions, and steric factors
-Starch folds into a helical structure stabilized by hydrogen bonds
-Hydrogen bonds are important in forming cellulose

Homopolysaccharides

contain only a single monomeric sugar species
-Serve as storage forms and structural elements

Heteropolysaccharides

contain 2+ kinds of monomers
-Provide structural support

Building polysaccharides

Structure is determined by their biosynthetic enzymes
-There is no template!
-In contrast with DNA, RNA, and proteins, which are synthesized using templates that direct their sequence.

Storing sugars

Storage of polymeric sugars prevents the high osmolarity that occurs when storing sugar monomers
-If the glucose in liver glycogen were monomeric, the glycose concentration in liver would be so high that cells would swell and lyse from the entry of water by osmosis.

storage polysaccharides

starch (plant cells) and glycogen (animal cells)

-Both are heavily hydrated- exposed hydroxyl groups hydrogen bond with water.

Amylose

long, unbranched chains of D-glucose residues connected by (α1->4) linkages

Amylopectin

larger than amylose with (α1->4) linkages between glucose residues and highly branched due to (α1->6) linkages.
-In plants

Glycogen

polymer of (α1->4)-linked glucose subunits, with (α1->6)-linked branches
-More extensively branched
-More compact than starch (needs to fit in your liver)
-In animals

Helical structure of starch and glycogen

most stable three-dimensional structure for the (α1->4)-linked chains of starch and glycogen
-Six residues/turn

Cellulose

a tough, fibrous, water-insoluble glucose polysaccharide

-Long, linear, unbranched homopolysaccharide

-Glucose residues have the β configuration

-Linked by (β1->4) glycosidic bonds

-Animals do not have the enzyme to hydrolyze (β1->4) glycosidic bonds

Chitin

Linear homopolysaccharide compose of N-acetylglucosamine residues in (β1->4) linkage
-Acetylated amino group makes chitin more hydrophobic and water-resistant than cellulose
-Exoskeletons

Linear structure of cellulose

Most stable conformation is a straight, extended chain
-Each chair is turned 180 relative to its neighbors
-Stabilized by hydrogen bonds

Peptidoglycan

is a rigid component of bacterial cell walls
-Heteropolymer
-Alternating (β1->4)-linked N-acetylglucosamine and N-acetylmuramic acid residues
-Cross-linked by short peptides - provides structural stability

Extracellular matrix (ECM)

A gel-like material in the extracellular space of tissues that holds cells together and provides a porous pathway for nutrient and O2 diffusion

-Composed of an interlocking meshwork of heteropolysaccharides and fibrous proteins

Basement membrane

specialized ECM that supports epithelial cells also contains heteropolysaccharides

Glycosaminoglycans (GAGs)

Heteropolysaccharides in ECM
-Linear polymers composed of repeating disaccharide units
-Highly polar and thus attract water
-Used as lubricants or shock absorbers in the body

Hyaluronan (hyaluronic acid)

Alternating residues of D-glucuronic acid and N-acetylglucosamine
-Used to treat burns and promote wound healing
-Type of GAG

Heparan sulfate

A highly sulfated glycosaminoglycan
-Sulfated residues allow the molecule to interact specifically with proteins
-Used as a therapeutic agent to inhibit coagulation of blood
-Provide viscosity, adhesiveness, and tensile strength to the ECM

Proteoglycan Aggregates

Supramolecular assemblies of many proteins bound tr a single molecule of hyaluronan

-Aggrecan interacts strongly with collagen on the ECM of cartilage

Antithrombin

inhibits thrombin (a protease)
-Only in the presence of heparan sulfate
-Heparan sulfate enhancement of binding of thrombin to antithrombin

Dextran

structural: in bacteria, gives rigidity and strength to cell envelope

Glycoconjugate

are biologically active molecules consisting of an informational carbohydrate joined to a protein or lipid

Proteoglycans

Macromolecules of the cell surface of ECM

- less than or equal to 1 sulfated GAG covalently bonded to a protein

-A major component of all extracellular matrices

Glycoproteins

Oligosaccharides covalently bonded to a protein.
-Used for cell signaling
-Heterogenous
-Rich in information

Glycolipids

lipids with oligosaccharide (hydrophilic) head groups
-Often in the plasma membrane

Glycosphingolipids

A class of glycolipids with specific backbone structure

-Found in neurons

-Play a role in signal transduction

Interactions between cells and the ECM

- anchor cells to the ECM, providing the strength and elasticity of skin and joints
- provide paths that direct the migration of cells in developing tissue
- convey information in both directions across the plasma membrane

Glycoproteins in the body

-Antibodies
-Follicle-stimulating hormone (FSH)
-Luteinizing hormone (LH)
-Thyroid-stimulating hormone (TSH)
-Milk proteins E.g. major whey protein α-lactalbumin
-Mucins - O-linked oligosaccharide chains, Secreted or membrane bound, Present in most secretions

Glycobiology

the study of the structure and function of glycoconjugates
-The goal is to understand how cells use specific oligosaccharides to encode information about:
-Intracellular targeting of proteins
-Cell-cell interactions
-Cell differentiation and tissue development
-Extracellular signals

Glycomics

the systemic characterization of all carbohydrate components of a given cell or tissue, including those attached to proteins and to lipids

Lipopolysaccharide

(LPS, endotoxin): A dominant surface feature of the outer membrane of gram-negative bacteria

-O antigen is recognized by the immune system and antibodies are generated against it

-Potent

-Can cause septic shock (& other negative effects)

Oligosaccharides structures

Commonly branched, unlike nucleic acids or proteins
-Meaning no branching structural backbone
-Does not include not R groups, prosthetic groups, etc

variety of oligosaccharides

large variety due to:
-Stereochemistry and position of glycosidic bonds
-Type and orientation of substituent groups
-Number and type of branches

Lectins

sugar binding proteins

-bind specific sugars/polymers

-can read sugar sequence code and mediate biological processes -Bind carbohydrates with high specificity and with moderate to high affinity

Lectin functons

-Cell-cell recognition
-Signaling
-Adhesion
-Intracellular targeting of newly synthesized proteins

Selectins

a family of plasma membrane lectins

-Mediate cell-cell recognition and adhesion

-Move immune cells through the capillary wall

-Mediate inflammatory responses

-Mediate the rejection of transplanted organs - "Selectins are selective about organ transplantation"

Fibronectin

-A multifunctional adhesive glycoprotein ECM structure

-Involved in tissue repair, regulating cell motility, and embryogenesis

-Binds fibrin, herparan sulfate, collagen, and integrins

Integrins

transmembrane proteins that mediate signaling between cell interior and ECM molecules

Lectin-Ligand interactions

play a role in leukocyte movement
-Cells will express specific receptors when they need leukocytes

Lectin Multivalency

-Lectin-Carbohydrate interactions are highly specific and often multivalent
-Multivalent= Several possible binding sites/interactions
-A single lectin molecules has multiple carbohydrate binding domains - Increase total affinity

Blood Typing

determined by the presence or absence of specific carbohydrate antigens on the surface of red blood cells (RBCs)
-Lectins selectively bind to these carbohydrate structures
-This interaction helps identify the type of antigens present on the RBCs
-foreign blood will cause immune response if not compatible

Lectins in blood typing

A drop of blood is mixed with a lectin solution that binds to a specific blood antigen.
If the lectin binds to the antigens on the surface of red blood cells, agglutination occurs (indicates the presence of that specific antigen)

AB blood

universal recipient