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+ lightàSugar + O2) Structure—cell walls and extracellular structures in plants, animals and bacteria Conjugation onto lipids, proteins—glycosylation – Molecular Recognition – Protein Folding – Solubility DNA – DNA backbone – 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 weights >1x106 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:

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

1 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 – 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 – 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

2 Derivatives of Monosaccharides: Deoxy Sugars Deoxy Sugars – 1 or more hydroxyl groups replaced by hydrogens – DNAà 2-deoxy-D-ribose – Occur in glycoproteins and polysaccharides Derivatives of Monosaccharides: Amino Sugars Amino Sugars – Contain an amino group instead of –OH group – 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. – Locks molecule in cell. – Nucleotides are phosphorylated (ATP, GTP…)

Derivatives of Monosaccharides: A Few More Examples Sugar Alcohols (Alditols) – Prepared by mild reduction – Can’t cyclize – Sweeteners (xylitol—gum) Sugar Esters (phosphate esters) – Metabolic intermediates – Sugar moiety of ATP/GTPs Acetal/Ketal/Glycosides – 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

 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 – sucrose = table sugar - glucose and fructose (alpha linkage) – 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 1à4 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 – Contain only one type of monosaccharide molecule (e.g. amylose, one of the main components of starch) Heteropolysaccharides – More than one kind of monosaccharide – 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 (Glcα1à6Glc) Structural Polysaccharides Ex.: Cellulose (Glcβ1à4Glc)—most abundant natural polymer (found in plants) – Insoluble, highly organized – Not digestible by humans—only ruminant animals

4 Other Structural Polysaccharides Chitin – 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 – Cride preparation called agar in food production – From marine algae - Repeating units of arabinoase (galactose and anhydrous galactose) – Used for chromatographic separation of large biomolecules--DNA Peptidoglycans Provide Structure for Bacteria Cell Walls Protective peptide-polysaccharide layer – 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 – 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 – Hyaluronic acid binding domains – 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 5