Biochem Chapter 9

tautomers

(structural isomers differing in location of hydrogen atoms and double bonds) and can interconvert via an unstable enediol intermediate As with glyceraldehyde (and other monosaccharides), the ketose and aldose forms are interconvertible via tautomerization in dilute alkali.

hemiacetal and Hemiketals

A hemiacetal results from reaction of an aldehyde with an alcohol. Hemiketals form similarly, from a ketone and an alcohol.

The hexoses exist primarily in ring forms under physiological conditions

As with the aldopentoses, two kinds of rings are found: five-membered furanoses and six-membered pyranoses. In each case, a and b anomers are possible.

configurational isomers

Cannot interconvert w/o breaking a bond and re-formation of covalent bonds; an example is diastereomers

D and L

D and L forms of a monosaccharide are nonsuperimposable mirror images and are called enantiomers. The most important naturally occurring saccharides are the D-enantiomers. the terms D and L were meant to indicate the direction of rotation of the plane of polarization of polarized light: D for right (dextro), L for left (levo). The designation is always with respect to some reference compound.

Pentoses

D-Arabinose Some plants, tuberculosis bacilli Plant glycosides, cell walls L-Arabinose Widely distributed in plants, Constituent of cell walls, plant glycoproteins bacterial cell walls D-Ribose Widespread, in all organisms Constituent of RNA and ribonucleotides D-Xylose Woody materials Constituent of plant polysaccharides

Tetroses

D-Erythrose Widespread The 4-phosphate is an intermediate in carbohydrate metabolism

Beta

Left, Above ring

Diastereomers

Molecules with different orientations about the carbons preceding this reference carbon are given separate names. Thus, threose and erythrose are two aldotetroses with opposite orientations about carbon 2. Stereoisomers of this kind, which are not mirror images, are called diastereomers.

Naming a Ketose

Often the ketose name is derived from the corresponding aldose name by insertion of the letters ul. Thus erythrose becomes erythrulose.

Alpha

Right, Below ring

epimers

Sugars of this type, differing in configuration about only one carbon

The enantiomers of glyceraldehyde:

The configuration of groups around the chiral carbon 2 distinguishes D-glyceraldehyde from L-glyceraldehyde. The two molecules are mirror images and cannot be superimposed on one another.

conformational isomers.

The different ring conformations produced by slightly different bond angles can interchange by a simple deformation of the molecule (no bond breakage)

mutarotation

The monosaccharides can undergo interconversion between the a and b forms, using the open-chain structure as an intermediate. This process is referred to as mutarotation. A purified anomer, dissolved in aqueous solution, will approach the equilibrium mixture, with an accompanying change in the optical rotation of the solution. Enzymes called mutarotases catalyze this process in vivo.

Fischer projection

The most compact way to represent enantiomers •In a Fischer projection the bonds that are drawn horizontally are imagined as coming toward you; those drawn vertically are receding.

Determining Stereoisomers

When monosaccharides contain more than one chiral carbon, the prefix D or L designates the configuration about the carbon farthest from the carbonyl group Adding one more carbon, we obtain the pentoses. The aldopentoses have three chiral centers; therefore we expect 2^3, or eight, stereoisomers—in four pairs of enantiomers. The aldopentoses have three chiral centers; therefore we expect 2^3, or eight, stereoisomers—in four pairs of enantiomers. Aldotetrose has 2 chiral centers, so 2^2 or 4 stereoisomers (L and D x 2) and 2 diasteriomers (D and D erythrose and threose) For every Diastereomer there are 2 enantiomers Amount of chiral centers are the amount of diastereomers, amount of Enantiomers are diastereomers multiplied by 2

Cell surface recognition factors:

a)Schematic view of a lipid membrane. b)Electron micrograph of the surface of an intestinal epithelial cell. The cellular projections, called microvilli, are covered on their outer surface by a layer of branched polysaccharide chains attached to proteins in the cell membrane. This carbohydrate layer, called the glycocalyx, is found on many animal cell surfaces. Glycoprotein: protein with a polysaccharide Play a role in cell recognition

Stereoisomers

are isomers that differ in spatial arrangement of atoms, rather than order of atomic connectivity. The rest are categories under this definition

Enantiomers

are the yellow to the white: chiral molecules that are mirror images and are non-superimposable

Amylose

c)A portion of a molecule of amylose, a glucose polymer (of glucose) found in starch. Long polymers of the monosaccharides, like the starch amylose are called polysaccharides Oligosaccharides and polysaccharides are also referred to as glycans. Strictly speaking, the term carbohydrate is reserved for compounds with the (CH2O)n empirical formula, while the term saccharide covers both these com- pounds and all derivatives of carbohydrates.

Monosaccharides

characterized by the presence of one carbonyl group (aldehyde or ketone) and one or more hydroxyl groups. (The suffix ose is commonly used to designate compounds as saccharides.)

Amino Sugars

derived from beta-D-glucosamine: Muramic Acid: Ether and carboxylic acid N-acetylmuramic acid: secondary amide and, Ether and carboxylic acid The modified sugars—especially the amino sugars—are most often found as monomer residues in complex oligosaccharides and polysaccharides.

R-S nomenclature:

describes absolute stereochemical configuration according to a set of defined rules. Priorities for groups common in carbohydrate chemistry are: SH > OR > OH > NH2 > CO2H > CHO > CH2OH > CH3 > H We view the molecule with the group of lowest priority away from us (H in our example). If the priority of the remaining three groups decreases clockwise, the absolute configuration is called R (from Latin rectus, "right"). If priority decreases counterclockwise, the configuration is S (from Latin sinister, "left"). preferred by biochemists Difficult to apply t o apply to molecules like pentoses 5C, tetroses 4C and triose 3C, for larger carbon sugars

Trioses are the simplest monosaccharides.

smallest molecules regarded as monosaccharides are the trioses, with n = 3. The two triose tautomers illustrate the difference between aldose and ketose monosaccharides, also called more descriptively aldotriose and ketotriose, respectively. The enediol intermediate through which they are interconverted is unstable and cannot be isolated. Represent the two major classes of monosaccharides. glyceraldehyde and dihydroxyacetone each have one carbonyl carbon and both have the same atomic composition. They are tautomers (structural isomers differing in location of hydrogen atoms and double bonds) and can interconvert via an unstable enediol intermediate The simplest compound with the empirical formula of the class (CH2O)n is found when n = 1. However, formaldehyde, H2C (double bond) O, has little in common with our usual concept of sugars; indeed, it is a noxious, poisonous gas.

Four major features distinguish disaccharides from one another:

1.The two specific sugar monomers involved, and their stereoconfigurations. The monomers may be of the same kind, as the two D-glucopyranose residues in maltose, or they may be different, as the D-glucopyranose and D-fructofuranose residues in sucrose. 2. The carbons involved in the linkage. The most common linkages are 1à 1 (as in trehalose), 1à 2 (as in sucrose), 1à 4 (as in lactose, maltose, and cellobiose), and 1à 6 (as in gentiobiose). Note that all of these disaccharides involve the anomeric hydroxyl of at least one sugar as a participant in the bond.

Formation of Pyranose and Furanose

A 5 carbon sugar will form a furose ring when the OH on C4 attacks the first carbon, ends up with the 5th carbon outside the ring attached to C4 A 6 carbon sugar will form a pyranose ring If the OH on C5 attacks the first carbon, ends up being a 6 membered ring Anomeric Carbon: carbon that was attacked nucleophically by the OH The hydroxide below the ring is alpha and above the ring is beta If on the fisher projection the OH are on the right, then on the haworth projection they will be below the ring, and if OH on the LEFT they will be above the ring

Writing the Structure of Disaccharides:

A convenient way to describe the structures of these and more complex oligosaccharides has been devised. The rules are as follows: 1.The sequence is written starting with the non-reducing end at the left. 2.Anomeric and enantiomeric forms are designated by prefixes (e.g., a-, D-). 3.The ring configuration is indicated by a suffix (p for pyranose, f for furanose). 4.The atoms between which glycosidic bonds are formed are indicated by numbers in parentheses between residue designations (e.g., (1 à 4) means a bond from carbon 1 of the residue on the left to carbon 4 of the residue on the right). Naming: beta or alpha, then D, then gluco "pyranosyl" or "pyranose"

Numbering Aldoses

Carbon numbering begins in all aldoses with the aldehyde carbon and in ketoses with the end carbon closest to the ketone group.

O-glycoside/glycosidic bond

Elimination of water between the anomeric hydroxyl of a cyclic monosaccharide and the hydroxyl group of another compound yields an O-glycoside. The acetal bond formed is referred to as a glycosidic bond. A simple example is the formation of methyl-a-D-glucopyranoside: Unlike the anomers of the sugars themselves, the anomeric glycosides (e.g., methyl-a-D-glucopyranoside in the example shown, and methyl-b-D-glucopyra- noside) do not interconvert by mutarotation in the absence of an acid catalyst, a property that makes them useful in the determination of sugar configurations.

uronic acids

Enzyme-catalyzed oxidation of monosaccharides gives other products, including uronic acids such as glucuronic acid, in which oxidation has occurred at carbon 6. Uronic acids are, as we see later in this chapter, important con- stituents of certain natural polysaccharides.

glycans

Just as monosaccharides can form glycosidic bonds with other kinds of hydroxyl- containing compounds, they can do so with one another. Such bonding gives rise to glycans—the oligosaccharides and polysaccharides. The simplest and biologically most important oligosaccharides are the disaccharides, made up of two residues. Sucrose, lactose, and trehalose, are soluble energy stores in plants and animals maltose and cellobiose, can be regarded primarily as intermediate products in the degradation of much longer polysac- charides gentiobiose, are found principally as constituents of more complex, naturally occurring substances.

Structural polysaccharides.

•Cellulose and chitin are examples of structural polysaccharides. • •Unlike starches, which have a(1à4) links, these fibrous polymers have b(1à4) linkages. A homopolymer of N-acetyl-b-D-glucosamine, chitin has a structure basically similar to that of cellulose, except that the hydroxyl on carbon 2 of each residue is replaced by an acetylated amino group.

The peptidoglycan layer of Gram-positive bacteria:

•Cross-links between the peptides are formed by pentaglycine chains between the a-amino group of the lysine (*) on one chain and the C-terminal carboxyl group of the alanine (**) on an adjacent chain. Long polysaccharide chains, which are strictly alternating copolymers of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM), are cross-linked through short peptides (see Figure 9.24a). These peptides have unusual structures. Attached to the lactic acid moiety of the N-acetylmuramic acid is a tetrapeptide with the sequence From the MurNAc, the oxygen to where L-alanine begins is the lactic acid (part of the muramic acid) as mentioned above The pentaglycine is between the peptidoglycan layers, the layers are connected as shown above The cell wall protects the bacteria from lysing The result is the formation of a covalently cross-linked structure that envelops the bacterial cell. The entire cell wall can be regarded as a single enormous molecule made up of multiple layers of cross- linked peptidoglycan strands.

The structure of a lipotechoic acid:

•D-Alanyl and NAG groups are arranged irregularly on the chain, which is anchored in the membrane by lipid. elongated lipid-oligosaccharide complex protrude from the membrane through the peptidoglycan wall. The first cyclic molecule is NAG and the protrusion in the middle is D-alanyl Lipid can be visualized all the way at the bottom The result is the formation of a covalently cross-linked structure that envelops the bacterial cell. Penicillin: inhibits bacterial growth by interfering with the formation of the peptidoglycan layer naturally occurring antibiotic substances acts not by interfering with cell wall synthesis but by attacking the peptidoglycan layer itself. These substances are the lysozymes, enzymes with wide distribution—they are found in bacteriophages, egg white, and human tears, for example. they help the phage to rupture an infected bacterium, releasing progeny phage at the conclusion of a lytic cycle of growth. Lysozymes catalyze hydrolysis of the glycosidic links between GlcNAc and MurNAc residues in the polysaccharide. Thus, they dissolve the cell wall, resulting in osmotic rupture of the membrane and bacterial death.

Writing the Structure of Disaccharides: 2

•For example, we can write the structure of sucrose as: a-D-Glcp(1à2)-b-D-Fruf •Often, the D and p or f are omitted under normal circumstances. when the monomers have their usual ring forms. • •For example, the structure of maltose can be written as: • Glca(1à4)Glc (except in the unusual cases in which L enantiomers are encountered) The system can be applied to oligosaccharides of any length and can include branched structures If only one carbon involved in the linkage between two residues is anomeric, the representa- tion can be even more condensed because the anomeric configuration at the reducing end will equilibrate in solution. For example, maltose can be represented as Glca(1 -> 4)Glc.

high energy phosphate

•For glycan biosynthesis those activated monomers are usually nucleotide-linked sugars. • •The activated sugar molecule in lactose biosynthesis is uridine diphosphate galactose (UDP-galactose or UDPGal), a nucleotide-linked sugar formed by reaction of uridine triphosphate with galactose-1-phosphate. Need hydrolysis of a high energy phosphate As in those cases, the reaction as written is thermodynamically unfavored. Instead, the hydrolysis of oligosaccharides and polysaccharides is favored under physiological conditions by a standard state free energy change of about 15 kJ > mol polysaccharides in vivo is controlled by the presence of specific enzymes. Furthermore, synthesis of these sugar polymers never proceeds in living cells by reactions like the one we have just shown. As in protein or nucleic acid synthesis, activated monomers are required Hence, there is a thermodynamic tendency for one of the bonds to break, and in the process the activated galactosyl moiety can be transferred to a carbohydrate acceptor.

Cellobiose, Lactose, Gentiobiose

(b) Disaccharides with b linkage: cellobiose, lactose, and gentiobiose. Note the convention used to draw glycosidic bonds between monomers in disaccharides. The "bent bonds" allow the Haworth projections of the monomers to be drawn in parallel. The "corners" do not imply extra carbon atoms, as they often do in organic structure rep- resentations. Pyranosyl or pyranose

glycosyltransferases

•Glycan biosynthesis is carried out by glycosyltransferases, enzymes that transfer an activated glycosyl moiety, such as UDP-glucose, to a specific position on a carbohydrate acceptor.

Cellulose structure:

Cellulose structure: •The b(1->4) linkages of cellulose generate a planar structure. Distinct from starch which was a1à4 and a1à6 • •The parallel cellulose chains are linked together by a network of hydrogen bonds. Like amylose, cellulose is a linear polymer of D-glucose (and hence is also a glucan) This arrangement is reminiscent of the b-sheet structure in silk fibroin, and as in fibroin, the fibrils of cellulose have great mechanical strength but limited extensibility. Cellulose can exist as fully extended chains, with each glucose residue flipped by 180 with respect to its neighbor in the chain. The major polysaccharide in woody and fibrous plants (like trees and grasses), plants don't synthesize fibrous structures, do not synthesize carotin and collagen rely on these polysaccharides Cellulose is a strong fiber is what gives vegetables and fruits their structure and is fiber which its eaten but not digested, Animal enzymes that are able to catalyze cleavage of the a(1 à 4) link in starch cannot cleave cellulose (the beta). For this reason, humans, even if starving, are unable to utilize the enormous quantities of glucose all around them in the form of cellulose. The insoluble fiber is quickly transported to the alimentary canal The bulk in fiber produces a feeling of satiety, or fullness, signaling when we have probably had enough to eat. Insoluble fiber increases the rate of transport of digestion products through the alimentary tract, by increasing its bulk, and is thought to reduce exposure to potential toxins or carcinogens in the diet. Termites and fungi that can cleave B sheets, Ruminants such as cows can digest cellulose only because their digestive tracts contain symbiotic bacteria that produce the necessary cellulases.

Hexoses

D-Galactose Widespread Milk (as part of lactose); structural polysaccharides L-Galactose Agar, other polysaccharides; Polysaccharide structures component of lactose D-Glucose Widespread Major energy source for animal metabolism; structural role in cellulose D-Mannose Plant polysaccharides, animal glycoproteins Polysaccharide structures D-Fructose A major plant sugar; part of sucrose Intermediate in glycolysis (phosphate esters)

Heptoses

D-Sedoheptulose Many plants Intermediate in Calvin cycle in photosynthesis and pentose phosphate pathway

Formation of the glycosidic bond between two monomers

Formation of the glycosidic bond between two monomers in an oligosaccharide is a condensation reaction, involving the elimination of a molecule of water. Thus, we might expect the synthesis of lactose to proceed as follows: Like the phosphodiester bond in nucleic acid and amide bond in proteins, the glycosidic bond is metastable. Enzymes control its hydrolysis. Galactose and glucose are ONLY different in the 4th carbon in which for galactose it is a B carbon and for glucose it is a A carbon This reaction is analogous to the elimination of water between amino acids in the formation of polypeptides or between nucleotides in the formation of nucleic acids. Metastable: (of a state of equilibrium) stable provided it is subjected to no more than small disturbances.

Trioses

Glyceraldehyde Widespread (as phosphate) The 3-phosphate is an intermediate in glycolysis Dihydroxyacetone Widespread (as phosphate) The 1-phosphate is an intermediate in glycolysis

Boat and Chair

Hexoses can exist in boat and chair conformations. Usually the chair is more stable. Bonds to substituents on ring carbons can then be classed as axial (a) or equatorial (e), depending on whether they are approximately parallel or perpendicular to the axis For most sugars, the chair form is more stable because substituents on axial bonds tend to be more crowded in the boat form.

Stereoisomers

In general, a molecule with n chiral centers will have 2n stereoisomers because there are two possibilities at each chiral center. Focus on the 3rd carbon since it is furthest and use its designation Stereoisomers are isomers that differ in spatial arrangement of atoms, rather than order of atomic connectivity. The rest are categories under this definition Enantiomers are the yellow to the white: chiral molecules that are mirror images and are non-superimposable Diastereomers Stereoisomer that is NOT a mirror image The aldose-ketose conversion also provides a route for interconversion of aldose diastereomers, using the ketose as an intermediate.

The energy cycle of life:

In photosynthesis, plants use the energy of sunlight to combine carbon dioxide and water into carbohydrates, releasing oxygen in the process. In respiration, both plants and animals oxidize the carbohydrates made by plants, releasing energy and re-forming CO2 and H2O. In photosynthesis, plants take up CO2 from the atmosphere and "fix" it into carbohydrates. as the light-driven reduction of CO2 to carbohydrate, here represented as glucose. Much of this carbohydrate is stored in the plants as polymeric starch or cellulose. Animals obtain their carbohydrates by eating plants or plant-eating animals. In the other half of the cycle, both plants and animals carry out, via oxidative metabolism, a reaction that is essentially the reverse of photosynthesis, to yield once again CO2 and H2O This oxidation of carbohydrates is the primary energy-generating process in metabolism.

D/L and R/S

In this notation, D-glyceraldehyde is R-glyceraldehyde, and L-glyceraldehyde is S-glyceraldehyde. **D becomes R, L becomes S

Stereochemical relationships of the D-ketoses:

Ketotetrose 1 chiral center, 2^1, or 2 stereoisomers, 1 Diastereomer and 2 enantiomers Ketopentose 2 chiral centers, 2^2 or 4 stereoisomers, 2 diastereomer and 4 enantiomers Often the ketose name is derived from the corresponding aldose name by insertion of the letters ul. Thus erythrose becomes erythrulose.

•Ouabain and amygdalin are highly toxic glycosides produced by plants.

Many glycosides are found in plant and animal tissues. Some are toxic substances, in most cases because they act as inhibitors of enzymes involved in ATP utilization. Ouabain inhibits the action of the enzymes that pump Na+ and K+ ions across cell membranes to maintain necessary electrolyte balance Necessary for electrolyte balance, Ouabain now finds use in treatment of some cardiac conditions

Haworth projections

Monosaccharides with five or more carbons exist preferentially in five- or six-membered ring structures (Haworth projections), resulting from internal hemiacetal formation. Two anomeric forms, and are possible, a and b. Rings containing fewer than five atoms are strained to a considerable extent, five- or six-membered rings are easily formed. In principle, aldotetroses can also form five-membered ring structures, but they rarely do. Two Ring closure reactions of the C-1 of D-ribose with the C-4 hydroxyl produces a five-membered ring structure called a furanose; the name reflects its structural similarity to the heterocyclic compound furan. Alternatively, a six-membered ring is obtained if the reaction occurs with the C-5 hydroxyl. Such a six-membered ring is called a pyranose, to indicate its relation to the heterocyclic compound pyran. The distribution between pyranose and furanose forms depends on the particular sugar structure, the pH, the solvent composition, and the temperature. Like other kinds of stereoisomers, these a and b forms rotate the plane of polarized light differently and can be distinguished in that way.

Repeating structures of some glycosaminoglycans:

•In each case, the repeating unit is a disaccharide, of which two are shown for each structure. First one is showing us N-acetylglucosamine a repeating pattern, contain sulfate or carboxyl groups that are derivatives The sulfate ester at position C6, are heteropolysaccharides Hyaluronic acid: N-acetylgalactosamine and Glucuronic acid 3 functions of Hyaluronic acid are the next 3 slides Taking chondroitin sulfate for extremities

anomers

Such isomers, differing in configura- tion only at the carbonyl carbon (C1 in this case), are called anomers, and carbon 1 is often referred to as the anomeric carbon atom.

intermediates in metabolism

Sugar phosphates are important intermediates in metabolism, functioning as activated compounds in syntheses. Heptose, called sedoheptulose, plays a major role in the fixation of CO2 in photosynthesis and Chapter and also in the pentose phosphate pathway the phosphate esters of the monosaccharides themselves are major participants in many metabolic pathways. these values are less negative than the free energy of hydrolysis of ATP (-31 kJ>mol); thus, ATP can act as a phosphate donor to monosaccharides. Because hydrolysis of the phosphate esters of sugars is thermodynamically favorable, these derivatives can behave as "activated" compounds in many metabolic reactions. Neg charge at neutral pH

Representative carbohydrates:

The 2 compounds shown here are composed entirely of C, H, and O, with glucose forming the monomer for the oligomer and the polymer. a)Glucose, a monosaccharide. b)Maltose, a disaccharide containing two glucose units. Formula can be simplified to (CH2O) n The simplest carbohydrates are small, monomeric molecules—the monosaccharides, typically containing from three to nine carbon atoms, which include simple sugars such as glucose If only a few monomer units are involved, we call the molecule an oligosaccharide.

Maltose, a a trehalose, Sucrose

The corners do not indicate an additional carbon, Trehalose is not a reducing sugar Structures of some important disaccharides. Ball- and-stick models are shown on the left, with anomeric oxygens in red. On the right are Haworth projectionsof the same molecules, with color-coded monomers: blue = glucose, yellow = fructose, teal = galactose. (a) Disaccharides linked through the C-1 of the a anomer: maltose, trehalose, and sucrose.

Enzymatic formation of lactose:

The reaction shown occurs in the formation of milk in mammary tissue. Galactose is phosphorylated by ATP, then transferred to uridine diphosphate (UDP). UDP-galactose transfers galactose to glucose, with the accompanying cleavage of a phosphate bond. The reaction is catalyzed by the enzyme lactose synthase.

chiral center of glyceraldehyde

The second carbon atom in glyceraldehyde carries four different substituents, so it is chiral, like the a-carbon in most a-amino acids. Therefore, glyceraldehyde has two stereoisomers of the type called enantiomers,

Organization of plant cell walls:

•Microfibrils of cellulose are embedded in a matrix of hemicellulose which is similar to heteropolymers • •Note that the fibers are laid down in a crosshatched pattern to give strength in all directions. constitutes a major structural material in the exoskele- tons of many arthropods and mollusks. Creates crosslinks for flexibility and strength

The four most common hexoses:

These Haworth projections represent the D enantiomers. Only the b anomers are shown. hexoses prefer the pyranose ring structure when in aqueous solution. Glucose and mannose differ from each other only in the configuration about C2. Sugars of this type, differing in configuration about only one carbon, are called epimers. Similarly, glucose and galactose are epimers, for they differ in configuration only about C4. The anomeric carbon on a ketose it is on carbon TWO 2!!!! It contains the free hydroxyl

Conformational isomers:

These models show two of the possible ring conformations for b-D-ribofuranose. In both of them, C-1, O, and C-4 define a plane. In the C-2 endo conformation (a), C-2 is above the plane. In the C-3 endo conformation (b), C-3 is above the plane. These isomers are the two most common conformations for ribose and deoxyribose in nucleic acids. A C-3 exo conformation would look like the figure in (b), but C-3 would be flipped below the plane. The above are Conformational can interconvert without breaking a bond; this is what the image represents

Stereochemistry of aldotetroses:

These molecules have two chiral carbons and thus have two diastereomeric forms, threose and erythrose, each with a pair of enantiomers; 4 stereoisomers in total When monosaccharides contain more than one chiral carbon, the prefix D or L designates the configuration about the carbon farthest from the carbonyl group carbon number 3 in this case. Isomers differing in orientation about other carbons are called diastereomers and given different names.

4. The configuration of the anomeric hydroxyl group of each residue.

This feature is especially important for the anomeric carbon(s) involved in the glycosidic bond. The configuration may be either a or b. This difference may seem small, but it has a major effect on the shape of the molecule, and the difference in shape is recognized readily by enzymes. For example, different enzymes are needed to catalyze the hydrolysis of maltose and cellobiose, even though both are dimers of D-glucopyranose. The configuration may be either a (as in the disaccharides shown in Figure 9.15a) or b (as in those in Figure 9.15b). In polysaccharides the anomeric orientation plays a critical role in determining the secondary structures adopted by these polymers.

Hyaluronic acid:

This structure binds collagen and holds collagen fibers in a tight, strong network. Binding involves electrostatic interactions between the sulfate and/or the carboxylate groups of the proteoglycan complex and the basic side chains in collagen. A major function of the glycosaminoglycans is the formation of a matrix to hold together the protein components of skin and connective tissue illustrates the protein-carbohydrate, or proteoglycan (composed of proteins and carbohydrates), complex in bovine cartilage The core proteins, in turn, have chondroitin sulfate and keratan sulfate chains covalently bound to them through serine side chains. Keratan sulfate and chondroitin sulfate are covalently linked to extended core protein molecules. The core proteins are noncovalently attached to a long hyaluronic acid molecule with the aid of a link protein. Small lines are keratin sulfate Larger lines are chondroitin sulfate both attached to the core protein through serine side chains!!! It is a filamentous structure built on a single long hyaluronic acid, extended core proteins, structure binds collagen Another function of glycosaminoglycans is that they absorb water because they're charged, Hyaluronic acid has other functions in the body besides being a structural component. The polymer is highly soluble in water and is present in the synovial fluid of joints and in the vitreous humor of the eye. It appears to act as a viscosity- increasing agent or lubricating agent in these fluids, possibly related to electrostatic repulsion among the many carboxylate groups in the polymer; cushions the impact of stepping or running when the pressure is released the water rebinds (on collagen or knees) Keratin sulfate and chorondrin (bound covalently) core noncovalently

glucosamine and galactosamine

Two amino derivatives of simple sugars are widely distributed in natural polysaccharides: glucosamine and galactosamine, derived from glucose and galactose, respectively. Sialic acid is seen in the coats of viruses The above basically form secondary amides

Oxidation of monosaccharides

can proceed in several ways, depending upon the oxidizing agent used. For example, mild oxidation of an aldose with alkaline Cu(II) (Fehling's solution) produces the aldonic acids, as in the following example: Free aldonic acids, such as gluconic acid, are in equilibrium in solution with lactones, which are cyclic esters, in this case involving the C1 carboxyl and the C5 hydroxyl. Sugar has been oxidized, the charge of the oxygen is -2 and the copper Cu2 is +1 (2), positive and negative charges have to add to zero Copper got reduced (aka received one more bond, went from 2+ to 2-), and oxygen oxidized Since the gluconic acid got oxidized it is considered a reducing sugar Reaction takes place in C1, the monosaccharide which has an open hydroxyl group that is NOT involved, it is a reducing sugar bc it has the ability to be oxidized **if the product is oxidized it is considered a reducing agent in the reactants****if the product is reduced it is considered a oxidizing agent in the reactants**

draw glycosidic bonds.

•Note the convention used to draw glycosidic bonds. • •The "bent bonds" allow the Haworth projections of the monomers to be drawn in parallel. • •The "corners" do not imply extra carbon atoms, as they often do in organic structure representations.

Glycoproteins

•Oligosaccharides and proteins can be linked to form glycoproteins in two ways: • oO-linked glycans are attached via threonine or serine hydroxyls. o oN-linked glycans via asparagine amino groups. serve multiple functions, including cell adhesion, signaling and the recognition of eggs by sperm cells. Immunoglobulin ex. Recoginizing diff tissues N-linked glycans are attached, usually through N-acetylglucosamine, or some- times through N-acetylgalactosamine, to the side chain amide group in an asparagine residue. A common sequence surrounding the asparagine is -Asn-X-Ser/Thr-, where X may be any amino acid residue. O-linked glycans are usually attached by an O-glycosidic bond between N-acetylgalactosamine and the hydroxyl group of a threonine or serine residue, although in a few cases— collagen, for example (Chapter 6)—hydroxylysine or hydroxyproline is employed. -The OH allows the linkage with the oligosaccharide Are covalently attached Immunoglobulins for ex have a carbohydrates attrached to the constant domain of the heavy chain Different types are recognized for proper tissue distribution of the immunoglobulin, he different types of immunoglobulins must be recognized, both for proper tissue distribution and for interaction with phagocytic cells, which will destroy the antigen-immunoglobulin complex.

alditols: Derivatives of the Monosaccharides

•Reduction of the carbonyl group on a sugar gives rise to the class of polyhydroxy compounds called alditols. Important naturally occurring ones are erythritol, D-mannitol, and D-glucitol, often called sorbitol. When sorbitol accumulates in the lens of the eye of a person with diabetes, it can lead to the formation of cataracts.

The ABO blood group antigens:

•The O oligosaccharide does not elicit antibodies in most humans. • •The A and B antigens are formed by addition of GalNAc or Gal, respectively, to the O oligosaccharide. • •Each of the A and B antigens can elicit a specific antibody. • •R can represent either a protein molecule or a lipid molecule. Example of cell marking by oligosaccharides, another function along with structure storage, R can represent either a protein molecule or a lipid molecule on the surface of RBC; The lipid portion of the molecule helps anchor the antigen to the out-side surface of erythrocyte membranes. Multicellular organisms need to be marked on their surfaces so they interact properly w other cells and molecules so it can also recognize its own cells from others The lipid portion of the molecule helps anchor the antigen to the out-side surface of erythrocyte membranes. It is these oligosaccharides that determine the blood group types in humans. Their presence in a blood sample is detected by blood typing—determining whether antibodies to a particular antigen cause the red cells of that blood sample to clump, or agglutinate. Humans can produce antibodies against the A and B oligosaccharides, but the O type are nonantigenic. Normally, a person does not produce antibodies against his or her own antigen but does produce them against the other antigen type. People with type O blood normally have antibodies against both A and B and thus can receive from neither. Those with AB type, because they carry both A and B antigens themselves, have antibodies against neither.

ABO

•The blood group substances are a set of antigenic oligosaccharides attached to the surfaces of red cells. Blood type O is the Universal donor Blood type AB is the universal acceptor

Amylopectin, a branched glucan:

•The branches in glycogen are somewhat more frequent and shorter than those in amylopectin, and glycogen is usually of higher molecular weight, but in most respects the structures of these two polysaccharides are very similar. **** With glycogen and amylopeptin, the branches will inhibit the helical formation, Amylose, amylopectin, and glycogen are all polymers of a-D-glucopyranose. They are homopolysaccharides of the class called glucans, the homopolymers of glucose; Mannan: Homopolymer of manose Xylan: Homopymer of xylose Amylopectin: polymers of a-D-glucopyranose, we are able to see a lot of NONreducing ends (not many free hydroxyl groups, not many reducing ends ); does not have a free hydroxyl group that can be oxidized, startch in plants Amylopectin and glycogen are both branched polymers, because they contain both (1 -> 4) links, some (1 -> 6). The reason why it is branched is because enzymes attack chains at the nonreducing end, the branched structure of Amylopectin and glycogen are similar, but even more branched, each molecule has a lot of nonreducing ends, and can be attacked simultaneously, will allow rapid mobilization of glucose when needed, glycogen Is similar but even more branches, inhibits helical formations bc of the brances Glycogen is more branched

Gram-negative bacterium

•The cell wall consists of a Gram-negative bacterium, E. coli, has a thin peptidoglycan layer and an outer lipid membrane. • •The cross-links here are between tetrapeptides attached to the N-acetylmuramic acid (NAM) residues in adjacent chains Gram-negative bacterial cell walls also contain peptidoglycan, but it is single-layered and covered by an outer lipid membrane layer This difference allows the Gram stain to be washed from Gram-negative bacteria.

Gram-positive bacterium

•The cell wall of a Gram-positive bacterium, S. aureus, consists of a thick peptidoglycan layer made up of polysaccharide chains and short peptides. • •The peptides are cross-linked by glycine pentapeptides. The nature of this cell wall is the basis for categorizing bacteria into two major classes: those that retain the Gram stain (a dye-iodine complex), which are called Gram-positive bacteria, and those that do not, which are termed Gram-negative Gram-positive bacteria have a cell wall with a cross- linked, multilayered polysaccharide-peptide complex called peptidoglycan at the surface, outside the lipid cell membrane; consists of a thick peptidoglycan layer made up of polysaccharide chains and short peptides running through it are the lipoteichoic acid, after that is the lipid bilayer membrane Lipoteichoic acid runs through the peptidoglycan wall The peptides are linked by glycine pentapeptides. Next to it is an enlarged figure strictly alternating copolymers of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM), are cross-linked through short peptides, we have a tetrapeptide and is crosslinked by a glycine tentapeptide

3. The order of the two monomer units, if they are different kinds.

•The glycosidic linkage involves the anomeric carbon on one sugar, but in most cases the other is free. • •The two ends of the molecule can be distinguished by their chemical reactivity. • •For example, the glucose residue in lactose, having a free anomeric carbon and thus a potential free aldehyde group, could be oxidized by Fehling's solution; the galactose residue could not be. • •Lactose is therefore a reducing sugar, and the glucose residue is at its reducing end. The other end is called the nonreducing end. • •In sucrose, neither residue has a potential free aldehyde group; both anomeric carbons are involved in the glycosidic bond. Therefore, sucrose is a nonreducing sugar. Key to finding if the sugar is a reducing sugar: Must have a free hydroxyl on the anomeric carbon

glycosaminoglycans

•The major structural polysaccharides in vertebrate animals are the glycosaminoglycans, formerly called mucopolysaccharides. • •Important examples are the chondroitin sulfates and keratan sulfates of connective tissue, the dermatan sulfates of skin, and hyaluronic acid. • •All are polymers of repeating disaccharide units, in which one of the sugars is either N-acetylgalactosamine or N-acetylglucosamine or one of their derivatives. • •All are acidic (anionic), through the presence of either sulfate or carboxylate groups.

The secondary structure of amylose:

•The orientation of successive glucose residues favors helix generation. • •Note the large interior core. • •Hydrogen bonds (not shown) stabilize the helix. Also starch in plants, NOT branched, so it favors a helix Amylose is a linear polymer involving exclusively a(1 -> 4) links between adjacent glucose residues. Has one single nonreducing end is used mainly for long- term storage of glucose, specific enzymes will attack at the nonreducing end releasing one glucose molecule at a time called "end-nibbling" (as opposed to internal cutting) prevents the continual breakup of the long polymers, which would lead to their complete solubilization. If the helical structure is cleaved in the middle the stabilization will mess up Can reduce; examples shown on first lecture Reason for structure is that glucose is a small molecule, it rapidly diffuses and if large quantities in the cell were present would give rise to a very large cell osmotic pressure, which would be deleterious in most cases and lead to cell swelling,

Polysaccharides

•The principal storage polysaccharides are amylose and amylopectin, which together constitute starch polysaccharides in plants, and glycogen, which is stored in animal and microbial cells. • •Both starch and glycogen are stored in granules within cells • •Glycogen is deposited in the liver, which acts as a central energy storage organ in many animals. • •Glycogen is also abundant in muscle tissue, where it is more immediately available for energy release. • •Glycogen and the components of starch—amylose and amylopectin—are storage polysaccharides. • •Amylose is linear; amylopectin and glycogen are branched. Others, like cellulose, chitin, and the polysaccharides of bacterial cell walls, are structural materials analogous to the structural proteins. It is simplest to consider these molecules in terms of their functional categories. the polymer is made from only one kind of monomer residue (b-D-glucose for cellulose); these kinds of polymers are referred to as homopolysaccharides. If two or more different monomers are involved, the polymer is called a heteropolysaccharide. glycans are distinctive in that they can form branched chains. The ability to branch, plus the numbers of functional groups on each monomer that can participate in bond formation, give polysaccharides amazing structural diversity, and this undoubtedly contributes to the large number of roles played by polysaccharides. Will begin with starch and polysaccharides have different linkages such as the glycosidic linkage between monosacharides and confer different properties at times

Carbohydrates have numerous functions in biochemistry:

•generating and storing biological energy •molecular recognition (as in the immune system) •cellular protection (as in bacterial and plant cell walls) •cell signaling •cell adhesion •biological lubricants •controlling protein trafficking •maintaining biological structure (e.g., cellulose).