Download What Roles Do Carbohydrates Play In Vivo

Carbohydrates
Of the macromolecules that we will cover in this class, those involving carbohydrates are the most abundant in nature.
Via photosynthesis, over 100 billion metric tons of CO2 and H2O are converted into cellulose and other plant products.
The term carbohydrate is a generic one that refers primarily to carbon-containing compounds that contain hydroxyl,
keto, or aldehydic functionalities.
• Carbohydrates can range in sizes, from simple monosaccharides (sugars) to oligosaccharides, to polysaccharides.
What Roles Do Carbohydrates Play In Vivo?
Energy—Photosynthesis, (CO2+ lightàSugar + O2)
Structure—cell walls and extracellular structures in plants, animals and bacteria
Conjugation onto lipids, proteins—glycosylation
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Molecular Recognition
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Protein Folding
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Solubility
DNA
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DNA backbone
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DNA capping
Carbohydrate Naming
Monosaccharides—simple sugars, can’t be broken down, molecular
formula (CH2O)n
Oligosaccharides—a few (2-10) monosaccharides linked together
(conventional names: disaccharide, etc.)
Polysaccharides—polymers of simple sugars. Can have molecular
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weights >1x10 g/mol
Monosaccharide Structure and Naming
The simplest aldose and ketose are both trioses—containing 3 carbon
atoms
HEXOSES are the most abundant sugar in nature (think: glucose)
Stereochemistry
Aldoses >3 carbons and Ketoses > 4 carbons all have chiral centers.
Nomenclature for sugars specifies chirality—compared to glyceraldehyde:
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Aldose and Ketose Tree – see your book for figure
Enantiomers and Diastereomers
Diastereomers have opposite conformations at one (epimers) or more chiral centers.
Diastereomers are NOT mirror images
Conformational Structures Emil Fisher - Nobel Prize 1891 Organic chemist who found the
structure of D glucose
Fisher projections - place most oxidized carbon on top
Haworth Structures: carbons counted from anomeric C to clockwise
from the oxygen in the ring (pyranose) or the #2 C for furanose
Cyclic Form of Monosaccharides: Aldoses
Recall hemiacetals:
Example: The aldohexose glucose undergoes an INTRAMOLECULAR
reaction to from a cyclic hemiacetal: a pyranose
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Cyclic Form of Monosaccharides: Ketoses
Sugars are Not Planar Structures
Remember—neither furanose nor pyranose rings of monosachharides are actually planar—they are puckered.
Recall from O-chem—bulky substituents on rings prefer to be in the equitorial vs axial positions
For β-­‐D-­‐glucose, all bulky groups can be in the equatorial position
Important monosaccharides Glucose - preferred source of energy for brain cells and cells without mitochondria
Fructose - ketose, 2x as sweet as sucrose. Sperm use this as major sugar/energy source for motility
Galactose - important for lacotose and glycolipid production
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galactosemia - genetic disorder in galactose metabolism leads to accumulation of galactose-1-phosphate in
liver results in liver damage. Another version of the disease results due to lack of galactose metabolism.
Galactose concentration builds up in blood leading to cataracts.
- Can result in severe mental retardation. Identification and galactose free diet helps Derivatives of Monosaccharides: Sugar Acids
Sugar Acids
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Free aldehydes on sugars are reducing reagents
Diabetics often analyze the amount glucose found in their blood/urine using kits that detect the amount of reducing sugars
present
Monosacch. Oxidized at C6 are –uronic acids: See Fig. 7.9
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Derivatives of Monosaccharides:
Deoxy Sugars
Deoxy Sugars
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1 or more hydroxyl groups replaced by hydrogens
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DNAà 2-deoxy-D-ribose
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Occur in glycoproteins and polysaccharides
Derivatives of Monosaccharides: Amino Sugars
Amino Sugars
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Contain an amino group instead of –OH group
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Large component of oligo- and polysaccharides (e.g. chitin)
Derivatives of Monosaccharides: Phosphoprylation
Phosphorylation - can form anhydride phosphoester bond.
phosphorylation alters ionic character.
AT –OH group.
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Locks molecule in cell.
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Nucleotides are phosphorylated (ATP, GTP…)
Derivatives of Monosaccharides:
A Few More Examples
Sugar Alcohols (Alditols)
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Prepared by mild reduction
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Can’t cyclize
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Sweeteners (xylitol—gum)
Sugar Esters (phosphate esters)
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Metabolic intermediates
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Sugar moiety of ATP/GTPs
Acetal/Ketal/Glycosides
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Formed when the hemiacetal/hemiketal sugars react with alcohols
Chemical Modifications
When named, structures are considered to have their reducing ends on the right. Locate the reducing ends of the
structures on the left if appropriate.
• The configuration of the anomeric carbon joining the first monosaccharide unit to the second is given (reading left to
right).
• The non-reducing residue is named, and five-and six-membered ring structures are distinguished by using “furano” or
“pyrano” prefixes.
• The two carbons joined by the glycosidic bond are indicated in parentheses, with an arrow connecting the two numbers.
• The second residue is then named.
• If there are subsequent residues, the subsequent glycosidic bonds are described by the same conventions
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Non-­‐reducing disaccharides are named as glycosides rather than glycoses. Note that a double-­‐headed arrow is used to denote sugars that are joined by their anomeric carbons, AND, it is necessary to specifiy the stereochemistry at both anomeric carbons.
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Oligosaccharides
Disaccharides—2 monosaccharides linked by a glycosidic bond
Important Disaccharides
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sucrose = table sugar - glucose and fructose (alpha linkage)
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lactose = milk sugar - galactose and glucose (beta linkage)
Lactose intolerance: lack of enzyme to break the ß glycosidic linkage - leads to bloating cramps and diarrhea
Important disaccharides:
Maltose - malt sugar, from breakdown of starch - 2 glucoses
Cellobiose - breakdown of cellulose 2 ß (1->4) glucose ß linkages serve as structural sugars, a linkages serve as storage
sugars
Glycosidic Bond Formation
Glycosidic Linkages
Most common linkages are 1à4 and 1à6, others possible
Shorthand notation:
Abbrev. for monosaccharide, α- or β- and appropriate #s of linked atoms (e.g Glcα1-6Glc)
Functional Oligosaccharides: Antibiotics
Polysaccharides (Glycans)
Homopolysaccharides/homoglycans
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Contain only one type of monosaccharide molecule (e.g. amylose, one of the main
components of starch)
Heteropolysaccharides
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More than one kind of monosaccharide
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Example: hyaluronic acid—connective tissue/extracellular matrix
Polysaccharides Can Form Branched Structures
Unique to polysaccharides—proteins and DNA are both linear polymers
Starch: Energy Storage is Easier in Polymer Bulk
Carbs stored as polysaccharides to reduce the osmotic pressure (which is dependent on # of
total molecules)—in plants most common is STARCH (10-30% a-amylose, 90-70%
amylopectin)
Amylose is a linear polymer that forms helices!
Animals store polysacch. Glycogen—highly branched and compact, found in liver and muscles
Bacteria/yeast—Dextran (Glcα1à6Glc)
Structural Polysaccharides
Ex.: Cellulose (Glcβ1à4Glc)—most abundant natural polymer (found in plants)
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Insoluble, highly organized
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Not digestible by humans—only ruminant animals
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Other Structural Polysaccharides
Chitin
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Found in shellfish exoskeletons, fungi cell walls
Also extended ribbon conformation
• Can be in parallel (reducing ends packed together at one end) or anti-parallel
Chitin is a linear homopolysaccharide composed of N-acetylglucosamine residues in b linkages.
Chitin differs chemically from cellulose only in the acetylated amino substituent at carbon 2.
It forms extended fibers that are similar to those of cellulose, and is found principally in hard exoskeletons of
arthropods.
One of the major structural differences between chitin and cellulose, is that naturally occuring cellulose is composed
of strands that pack against each other in parallel (non-reducing ends are together at one end), whereas chitin occurs
naturally in both parallel and antiparallel stacking arrangements
Agarose
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Cride preparation called agar in food production
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From marine algae
- Repeating units of arabinoase (galactose and anhydrous galactose)
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Used for chromatographic separation of large biomolecules--DNA
Peptidoglycans Provide Structure for Bacteria Cell Walls
Protective peptide-polysaccharide layer
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Gram-Positive: thick peptidoglycan layer (25 nm)
Gram-Negative: thinner peptidoglycan (2-3 nm)
Peptidoglycans Provide Structure for Bacteria Cell Walls
Glycoproteins
Linked to hydroxyl groups of Ser, Thr or hydroxylysine (O-linked)
Linked to amide nitrogen of Asn (N-linked)
N-Linked: Calnexin/Calreticulin Cycle
N-Linked: Protein Folding Assistance
Glycans can alter protein solubility, charge, and mass
Protect from proteolysis
Co-translational modification promotes proper protein folding around glycosylation site (reduced degrees of freedom,
conformational rigidity)
O-Linked: Extracellular Rigidity and Cell Signaling
Cell surface glycoproteins
• Protect cell from unwanted
interactions
• Extracellular interactions/
signal transduction
O-GlcNAc signaling alters transcription/translation, signal transduction, metabolism
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Altered in cancer and diabetes
Proteoglycans: Glycosaminoglycan (GAG) Proteins
Vary widely in size and function
Either soluble and in extracellular matrix, or integral membrane proteins
Many GAGs have chondroitin sulfates—important for joint health
Proteoglycans in Cartilage
Proteoglycans confer both resilience and flexibility to our cartilage tissue
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Hyaluronic acid binding domains
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Proteoglycan-hyaluronic acid aggregates are highly hydrated
When our joints are compressed, water is squeezed out, but thanks to these proteoglycan-hyaluronic acid aggregates,
can be quickly reabsorbed
Shock-absorber, and reduces friction
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