Carbohydrates © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 4 NOT for SALE OR DISTRIBUTION NOT for SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Carbohydrates © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 4 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

CHAPTER OUTLINE 4.1 Monosaccharides© Jones & Bartlett Learning, LLC SUMMARY © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 4.2 Ring Formation in Sugars KEY TERMS 4.3 Disaccharides REVIEW QUESTIONS 4.4 ©Polysaccharides Jones & Bartlett Learning, LLC REFERENCES© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION linear polysaccharides BOX 4.1: Stereochemical Conventions: Little d/l branched polysaccharides BOX 4.2: WORD ORIGINS: Reducing © Jones &4.5 Bartlett Carbohydrate Learning, Derivatives LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FORBOX SALE 4.3: OR The DISTRIBUTION Irony of Intramolecular Simple Modifications Hydrogen Bonds

Substituted Carbohydrates BOX 4.4: Medical Connections: Sugars and Digestion © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORImage SALE © Dr. OR Mark DISTRIBUTION J. Winter/Photo Researchers, Inc. NOT FOR SALE OR DISTRIBUTION 43 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION arbohydratesNOT FOR are SALEmost commonly OR DISTRIBUTION encountered as the sweetener sucrose and as starch, the nutrient of bread and pasta. The Ccarbohydrates are literally hydrates of carbon, having the empirical formula CH2O. Because they posses both hydroxyl and carbonyl groups, they are a step up in complexity from lipids. Unlike © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC lipids, carbohydrates are generally very soluble in water. The direct NOT FOR SALEtranslation OR DISTRIBUTION of sugar into Latin is saccharide, NOTwhich FOR remains SALE in common OR DISTRIBUTION use in the term polysaccharides. Sugars are key nutrients in both animals and plants. Animals use sugars for rapid (i.e., minute-to-minute) energy production and © Jones & Bartlett Learning,lipids LLC for long-term storage.© Plants Jones use & sugars Bartlett for energyLearning, exclusively, LLC NOT FOR SALE OR DISTRIBUTIONexcept at the seed stage. BecauseNOT FOR sugars SALE are more OR denseDISTRIBUTION than lipids (having more oxygen atoms), and often associate with water, their greater weight impairs mobility. Hence, lipids are the long-term energy source used for mobile lifestyles (i.e., animals and plant seeds), and © Jones & Bartlett Learning, LLC carbohydrates© Jonesare the immediate& Bartlett energy Learning, source LLC for animals. NOT FOR SALE OR DISTRIBUTION Aside fromNOT providing FOR SALE energy, OR sugars DISTRIBUTION have a wide variety of roles once they are chemically modified, such as cell–cell recognition and signaling. Sugars attached to lipids comprise specific blood groups, and sugars are covalently linked to proteins secreted from cells. The basis for understanding sugars rests on the study of the simplest ones: © Jones & Bartlettthe monosaccharides.Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Monosaccharides © Jones & Bartlett Learning,4.1 LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONMonosaccharides have a singleNOT carbonyl FOR SALE group, OR which DISTRIBUTION occurs at the first or second carbon atom. All remaining carbons have an attached Table 4.1 General Nomenclature hydroxyl group. There are two classes of monosaccharides, called of Sugars aldoses and ketoses. Aldoses (aldehydes) have the carbonyl at carbon one, whereas ketoses (ketones) have the carbonyl at carbon two. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Carbons Sugar Category Name The “ose” suffix (as in aldose and ketose) is commonly used to NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 3 Triose define a compound as a sugar. The general category name for sugars 4 Tetrose is shown in Table 4.1, starting with the smallest, triose. Exceptions 5 Pentose to this naming rule are found in the simplest monosaccharides: dihydroxyacetone and glyceraldehyde (Figure 4.1). 6 Hexose © Jones & BartlettDihydroxyacetone Learning, LLC is a symmetrical molecule,© Jones because & Bartlett a plane Learning, LLC 7 HeptoseNOT FOR SALEof OR symmetry DISTRIBUTION can be drawn through its centralNOT carbon FOR SALEatom. Glycer OR DISTRIBUTION- 8 Octose aldehyde, however, has an asymmetric central carbon, called chiral (Latin for handedness). Any carbon to which four distinct groups are attached is a chiral center. As drawn in two dimensions, two different © Jones & BartlettO Learning,forms LLC of glyceraldehyde can© Jonesbe represented & Bartlett in a Learning,Fischer projection LLC , shown in Figure 4.2. The molecule on the left is called l, whereas NOTOHC FOR SALEC OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION the one on the right is called d, an arbitrary but agreed-upon OC OHC convention. The letters themselves stand for Levo and Dexter, from the Latin for “left” and “right.” In three dimensions, the four groups OHC OHC attached to the chiral carbon are spatially as far apart from one © JonesDihydroxyacetone & Bartlett Learning,Glyceraldehyde LLC another as possible,© Jones because & Bartlett the bonding Learning, electrons LLC repel each other. NOTF IGUREFOR 4.1SALE Triose OR Sugars. DISTRIBUTION Each group NOTattached FOR to theSALE chiral OR carbon DISTRIBUTION is at the corner of a virtual

44 Chapter 4 CARBOHYDRATES 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORtetrahedron, SALE OR asDISTRIBUTION shown in Figure 4.3. Note that carbonNOT FORnumber SALE 1 is OR FischerDISTRIBUTION projection assigned, by chemical convention, to the most oxidized carbon in Mirror image the molecule. In the case of a ketose, the carbonyl becomes carbon number 2. O O The two forms of glyceraldehyde are called l-glyceraldehyde © Jones & Bartlett Learning, LLC © JonesCH & BartlettCH Learning, LLC and d-glyceraldehyde. They are mirror reflections or enantiomers ** (indicated in FigureNOT 4.2) ofFOR each SALE other. OR As aDISTRIBUTION result, the two are not HONOTC FORH SALEH ORC DISTRIBUTIONOH

superimposable on each other, just as your left and right hands are CH2OH CH2OH not superimposable on each other.

Enantiomers share many chemical properties, such as identical L-Glyceraldehyde D-Glyceraldehyde melting© Jones and boiling & Bartlett points. Learning, They were LLCfirst identified through their© Jones & Bartlett Learning, LLC distinctNOT interaction FOR SALE with polarizedOR DISTRIBUTION light. Polarized light is producedNOT by FOR3D view SALE OR DISTRIBUTION special filters that eliminate all light rays other than those oriented O O in one plane. Experimentally, the interaction of a compound with polarized light is measured as degrees of rotation from a reference point, CH CH and a separate naming system is used (Box 4.1). From a biochemical © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC** perspective, the greatest significance of enantiomers is their selec- HO C H H C OH NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION tive interaction with enzymes. For example, most living systems can CH2OH CH2OH metabolize d-sugars, but not l-sugars. Larger sugar molecules (e.g., those with four or more carbon atoms) L-Glyceraldehyde D-Glyceraldehyde

have multiple chiral carbons. Figure 4.4 shows the Fischer projection FIGURE 4.2 d- and l-Glyceraldehyde. For each of a four-carbon sugar© Jones (a tetrose). & Bartlett It is an Learning, aldose because LLC it has an form, the Fischer© Jones projection & Bartlett is shown Learning, above a LLC aldehyde group at theNOT first FOR carbon. SALE The OR next DISTRIBUTION two carbons are both representationNOT of FORthe three-dimensional SALE OR DISTRIBUTION view. chiral, as indicated with asterisks. The convention for naming such a Chiral carbons are indicated by asterisks. sugar unambiguously is to first differentiate d-sugars from l-sugars. The carbon furthest from the carbonyl determines if the entire a molecule© Jones is d or & l Bartlett. In this example, Learning, it is LLC carbon 3. By comparing this© Jones & Bartlett Learning, LLC moleculeNOT toFOR glyceraldehyde, SALE OR DISTRIBUTION as indicated, the molecule is a d-sugar.NOT FOR SALE OR DISTRIBUTION All that remains is to resolve the ambiguity of the remaining chiral d center. This is done by simply assigning a name to the molecule: C this one is called erythrose. Our focus will be on d-sugars because they are far more common than l-sugars. The other four-carbon b © Jones &d-sugars Bartlett are Learning, d-threose and LLC d-erythrulose, shown in© Figure Jones 4.5 &. Unless Bartlett Learning, LLC NOT FORwe SALE are making OR DISTRIBUTION an explicit stereochemical point, weNOT will usuallyFOR SALE omit OR DISTRIBUTIONc the d indicator. FIGURE 4.3 Tetrahedral Carbon. The carbon Sugars that differ at chiral centers other than the d and l positions with four substituents, each as far apart from are called epimers. Thus, threose (Figure 4.5) is the epimer of erythrose one another as possible, forms a tetrahedron in space. (Figure 4.4). Larger ©sugars Jones have & correspondinglyBartlett Learning, greater LLC numbers of © Jones & Bartlett Learning, LLC isomers, but the namingNOT conventions FOR SALE hold. OR After DISTRIBUTION assigning the d and NOT FOR SALE OR DISTRIBUTION l forms, each molecular arrangement of the remaining chiral centers has a unique name. Examples of commonly occurring d-sugars are shown in Figure 4.6: ribose, glucose, galactose, and fructose. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 4.2 Ring Formation in Sugars Sugars having five or more carbons exist in solution primarily in a © Jones &ring Bartlett form. The Learning, reaction LLCthat leads to ring formation© Jones in sugars & Bartlettis an Learning, LLC NOT FORintra SALEmolecular OR DISTRIBUTION version of the more general one thatNOT forms FOR hemiacetals SALE OR DISTRIBUTION

chapter 4 CARBOHYDRATES 45 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION BOX 4.1: StereochemicalNOT FOR SALE Conventions: OR DISTRIBUTION Little d/l

In addition to the d/l naming convention, a separate system uses the lower case letters d and l (alternatively, + and -) to refer to the direction of rotation of plane- polarized light: d or for clockwise and l or for counterclockwise. To better © Jones & Bartlett Learning, LLC+ - © Jones & Bartlett Learning, LLC understand the use of the d/l system, consider the following practical experiment. NOT FOR SALE ORSuppose DISTRIBUTION you take a pair of polarized sunglasses, NOTpop out FOR the lenses, SALE and ORplace DISTRIBUTION them at either end of a tube filled with water (Figure B4.1). This device you have just made is a polarimeter. If you look through the tube, rotating one sunglass lens will entirely eliminate the light that gets through at a particular point. If you continue © Jones & Bartlett Learning, LLCto rotate it, light will appear again© until,Jones with &continued Bartlett rotation, Learning, it darkens LLConce NOT FOR SALE OR DISTRIBUTIONagain. Mark the darkest point. ThisNOT is whereFOR theSALE polarized OR planes DISTRIBUTION in the lenses are at right angles to one another. This follows from the operation of a Polaroid filter, which allows light beams to travel only in one direction. If you now replace the water in the tube with a solution of an optically active (chiral) molecule, and start with the marked point, one lens will have to be rotated to some extent to © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC restore the dark point. That displacement is measured in degrees, right or left NOT FOR SALE OR DISTRIBUTION (i.e., d or l ). NOTThis is causedFOR SALE by the interaction OR DISTRIBUTION of light with the molecules, and reveals the presence of asymmetrical interactions in the solution.

Polarizing glasses © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

(a)

Light Light © Jones & Bartlett Learning, LLC © JonesWater & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION (b)

Light Water Maximum dark © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC (c) NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Light Glucose Maximum dark

© Jones & BartlettFIGURE Learning, B4.1 Polarimetry. LLC A pair of polarizing sunglasses© Jones (or& untintedBartlett Learning, LLC polarizing glasses) can be used as polarized filters. Removing the lenses NOT FOR SALE ORand placingDISTRIBUTION each on opposite sides of a sealed NOTtube filled FOR with SALE solution OR DISTRIBUTION is the essence of a polarimeter. Its operation is shown in three situations. (a) The tube is filled with water. Both of the filters are oriented so that maximal light passes through. The polarization is indicated by lines on the filters, showing that they are in parallel. (b) Again, the tube is filled © Jones & Bartlett Learning, LLCwith water. The filters are oriented© Jones at 90 °& to Bartlett one another, Learning, in which case LLC NOT FOR SALE OR DISTRIBUTIONno light passes through. (c) NOTThe tube FOR is filled SALE with ORa glucose DISTRIBUTION solution. In this case, the point of maximum darkness is achieved by rotating one filter clockwise; this indicates that glucose is a d-sugar or, equivalently, a + sugar. Because this is independent of its d/l status, we would call this d-(+)-glucose. The same experiment performed with fructose would show © Jones & Bartlett Learning, LLC that the filter© would Jones have & to Bartlett be rotated Learning, counterclockwise; LLC hence, fructose is d-(-)-fructose. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

46 Chapter 4 CARBOHYDRATES 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORor SALE hemiketals OR DISTRIBUTION(Figure 4.7). As described in the figure,NOT the reaction FOR SALE joins OR DISTRIBUTIONO 1 a carbonyl group with a hydroxyl group (a nucleophilic substitution). CH

Note that the carbonyl oxygen becomes a hydroxyl group in the product. 2 The carbonyl carbon of the straight chain form becomes the HC* OH 3 anomeric carbon in the ring form. Because both the carbonyl group H C* OH and the alcohol group© Jonescome from & Bartlett the same Learning, molecule, theLLC hemiacetal © Jones & Bartlett Learning, LLC 4 or hemiketal reactionNOT is more FOR favorable SALE thanOR ifDISTRIBUTION the reactants were from NOT FORCH SALE2OH OR DISTRIBUTION

different molecules. The other consequence of this intramolecular D-Erythrose reaction is that the product becomes a ring. Of the different OH groups that could join with the carbonyl, only five- and six-membered rings O O are stable.© Jones Open & andBartlett ring formsLearning, for the LLC sugars fructose and glucose© Jones & Bartlett Learning, LLC are shownNOT FORin Figure SALE 4.8 .OR DISTRIBUTION NOT FOR SALECH OR DISTRIBUTIONCH The representation of ring forms as joined, straight-chain diagrams HO *C H H *C OH in Figure 4.8 is unrealistic. Most commonly, sugar rings are drawn as CH OH CH OH Haworth projections, as shown in the middle structure of Figure 4.9. 2 2 When constructing this diagram, you need only place the groups © Jones &appearing Bartlett on Learning, the right side LLC of the straight-chain Fischer© projectionJones & belowBartlett Learning,L-Glyceraldehyde LLC D-Glyceraldehyde NOT FORthe SALE ring inOR the DISTRIBUTION Haworth projection to achieve the correctNOT FOR orientation. SALE ORFIGURE DISTRIBUTION 4.4 d-Erythrose. The configuration at Note that the Haworth is a simplified representation of the more carbon 2 defines this structure as erythrose; realistic chair form, also shown in Figure 4.9. the configuration at carbon 3, the one furthest from the carbonyl, defines this as We now turn our attention to the hydroxyl group that is connected the d form. The reference compounds, l- and to the anomeric carbon,© Jones colored & Bartlettblue in these Learning, diagrams. LLC Because the d-glyceraldehyde,© Jones are shown& Bartlett for comparison. Learning, LLC anomeric carbon hasNOT become FOR a SALE new chiral OR DISTRIBUTIONcenter in the ring form, Chiral carbonsNOT are FOR indicated SALE by asterisks.OR DISTRIBUTION this hydroxyl group can have two distinct stereochemical forms (Figure 4.10). If the hydroxyl group is on the opposite side of the ring from the position determining the D-form of the sugar, it is called the O

alpha form. If the hydroxyl group is on the same side of the ring as C C OH the position© Jones determining & Bartlett the Learning, D-form of LLCthe sugar, it is called the beta© Jones & Bartlett Learning, LLC form.NOT As drawn FOR inSALE the Haworth OR DISTRIBUTION projection shown, the alpha-hydroxylNOT FORHO SALE C OR DISTRIBUTIONC O

group is below the ring, and the beta-hydroxyl group is above the OHC C OH ring. The alpha and beta forms are in equilibrium with each other as well as with the open-chain form, so that, metabolically, any of them OHC OHC can be utilized in reactions. Figure 4.10 provides the full name of © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning,D-Threose LLC D-Erythrulose the sugar, with both the designation d (to identify its stereochemical NOT FOR SALE OR DISTRIBUTION NOT FOR SALE ORFIGURE DISTRIBUTION 4.5 d-Threose and d-Erythrose. similarity to d-glyceraldehyde) as well as the a and b forms resulting from ring formation.

C OHC OHC C O

OHC HO C HO C HO C © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC OHC OHC HO C OHC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION OHC OHC OHC OHC

OHC OHC OHC OHC

Ribose Glucose Galactose Fructose

© Jones &FIGURE Bartlett 4.6 Common Learning, Monosaccharides. LLC Only the d forms© ofJones these common& Bartlett Learning, LLC NOT FORsugars SALE are OR shown, DISTRIBUTION because they are the prevailing biologicalNOT isomers. FOR SALE OR DISTRIBUTION

chapter 4 CARBOHYDRATES 47 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORO SALE ORO DISTRIBUTION— OH To summarize,NOT FOR we have SALE discussed OR DISTRIBUTION three types of stereochemistry that allow us to unambiguously identify a sugar: C R C R H+ C R + 1. d or l, which refers to the configuration of the chiral carbon O O furthest from the carbonyl group OH H+ C © Jones C& Bartlett 2.Learning, Different namesLLC for other epimers (e.g.,© Jones mannose & Bartlettor galactose) Learning, LLC C NOT FOR SALE OR3. DISTRIBUTION Alpha or beta, which refers to the configurationNOT FOR of SALE the anomeric OR DISTRIBUTION carbon

The ring forms of ribose and fructose, shown as Figure 4.11, are also in equilibrium with their open-chain forms. The fact that common OH OH © Jones & Bartlett Learning,sugars LLC like these form rings© is Jones important & Bartlett not merely Learning, because LLCthis is NOTC H FOR SALEC CORX DISTRIBUTIONthe predominant solution form,NOT but FOR also SALE because OR the DISTRIBUTION hydroxyl group O O attached to the anomeric carbon is used in bonding sugars together. The first example of this kind of linkage is in the disaccharides. C C

Hemiacetal Hemiketal © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC FIGURE 4.7 Hemiacetal and Hemiketal NOTFormation. FOR SALE The reaction OR DISTRIBUTION of an alcohol group NOT FOR SALE OR DISTRIBUTION with a carbonyl is one of simple nucleophilic 4.3 Disaccharides substitution. Two sugars bonded together are called disaccharides; some examples are shown in Figure 4.12. Of these, the best known is sucrose; it © Jones & Bartlettis what Learning, we popularly LLC call “sugar” itself.© Sucrose Jones is & widely Bartlett found Learning, LLC 1 1 C OH NOTC FOROH SALEin OR plants DISTRIBUTION but is heavily concentrated in NOTjust a FORfew, suchSALE as ORsugar DISTRIBUTION 2 2 C O HO C cane and sugar beets. Maltose is a product of the partial digestion

3 3 of starch and is common in the production of beer. The partial HO C HO C O digest itself is called a “malt,” hence the name “malt liquor.” 4 4 ©OHC Jones & Bartlett Learning,OHC Lactose LLC is milk sugar, which© is Jonesproduced & byBartlett mammals Learning, for feeding LLC their newborn. Trehalose is uncommon in plants but found in bacteria, 5 NOTOHC FOR SALE5 COR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION fungi, and invertebrates and plays a role analogous to sucrose in those 6 OHC 6 OHC organisms. Fructose In each of these disaccharides, one of the sugar units is glucose; (hemiketal) the other is glucose, galactose, or fructose. The linkage between the © Jones & Bartlett Learning, LLC two sugars is© called Jones a glycosidic & Bartlett bond Learning,. The glycosidic LLC bond of maltose, NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION O

1 1 C HO C 1 2 2 HO C OHC OHC OH 2 3 © Jones3 & Bartlett Learning,C OH LLC 6 © Jones & Bartlett Learning, LLC HO C HO C O 5 3 O NOT FOR SALE OR DISTRIBUTIONO OH NOT FOROH SALE OR DISTRIBUTION 4 4 HO C 4 4 OHC OHC OH 6 O 4 1 5 5 5 OHC HO OH OHC C HO OH 5 3 2 2 1 6 6 C OHC OHC OH 3 OH 6 © Jones & Bartlett Learning, LLC OHC © Jones & Bartlett Learning, LLC Glucose NOT FOR SALE(hemiacetal) OR DISTRIBUTIONGlucose GlucoseNOT FOR SALE OR DISTRIBUTIONGlucose Straight-chain Hayworth projection Chair form FIGURE 4.8 Ring Formation in Sugars. The reaction shown in Figure 4.7 takes place FIGURE 4.9 Views of Sugar Rings. The straight-chain form (Fischer projection) intramolecularly in sugars having at least can be recast as the Hayworth projection by taking groups positioned to the five carbons. Because the aldehyde and right in the Fischer projection above the ring, and those to the left below it. © Jonesalcohol & are Bartlett part of the Learning, same molecule, LLC The chair form© isJones a solution & Bartlett structure Learning,that more closely LLC represents the NOTthe FOR product SALE is a ring.OR DISTRIBUTION three-dimensionalNOT structure FOR SALE of the sugarOR DISTRIBUTION molecule.

48 Chapter 4 CARBOHYDRATES 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

OH 6 5 O O OH O OH O 4 1 1 © Jones & BartlettOH Learning, LLC © Jones & Bartlett Learning,OH LLC C NOT FOR SALEHO OR DISTRIBUTIONOH NOT FOR SALE OR DISTRIBUTION 2 OHC 3 2 OH

3 OH HO C OH OH OH OH α-D-Glucose 4 α-Ribose β-Ribose OHC © Jones & Bartlett Learning,OH LLC © Jones & Bartlett Learning, LLC 5 NOT FOR SALEOHC OR DISTRIBUTION6 NOT FOR SALE OR DISTRIBUTION 6 5 O OH O OH O OHC OH CH2OH OH 4 OH Glucose 1 HO HO HO OH CH2OH 3 2 © Jones & Bartlett Learning, LLC OH© Jones & Bartlett Learning,OH LLC OH NOT FOR SALE OR DISTRIBUTION β-D-Glucose NOT FOR SALE OR DISTRIBUTIONα-Fructose β-Fructose FIGURE 4.10 Multiple Ring Forms of Glucose. Two separate ring forms of FIGURE 4.11 Ring Forms of Ribose and glucose are possible, depending on which face of the carbonyl is attacked Fructose. by the hydroxyl group attached to carbon 5. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION OH OH OH OH

O O O O OH 1 4 11 © Jones & BartlettOH Learning, OHLLC ©OH Jones & BartlettOH Learning, LLC NOT FORHO SALE OR DISTRIBUTIONO OH HO NOT FOR SALEO OR DISTRIBUTION OH OH OH OH Maltose Trehalose Glucose (α1 4) Glucose Glucose (α1 1) Glucose

© Jones & Bartlett Learning, LLC OH © Jones & BartlettOH Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION OH O O 4 OH OH 1 O HO O OH HO OH 1 O © Jones & Bartlett Learning,OH LLC OH © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION OH O NOT FOR SALE OR DISTRIBUTION OH 2 HO Lactose CH2OH Galactose (α1 4) Glucose © Jones & Bartlett Learning, LLC © JonesOH & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT SucroseFOR SALE OR DISTRIBUTION Glucose (α1 β2) Fructose FIGURE 4.12 Disaccharides. The two sugars in the disaccharide are linked by a glycosidic bond. This locks the anomeric hydroxyl in either the alpha or the beta configuration. Either one (maltose and lactose) or both (sucrose and trehalose) sugar units have their anomeric carbons in a glycosidic bond. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

chapter 4 CARBOHYDRATES 49 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION for example,NOT is formally FOR a SALE removal OR of waterDISTRIBUTION from two glucose molecules, as indicated in Figure 4.13. The metabolic route to glycoside formation involves energy input and intermediate steps. Once a disaccharide has formed, the stereochemistry of the anomeric carbon involved in the glycosidic bond is fixed: it is either © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC a or b, as indicated in Figure 4.12. The notation for the glycosidic NOT FOR SALEbond OR DISTRIBUTIONbetween the sugars provides the numberNOT of theFOR anomeric SALE carbonOR DISTRIBUTION (with its a or b oxygen position indicated) separated by an arrow from the number of the connected carbon on the other sugar. Only one of the anomeric carbons is involved in the glycosidic bonds of © Jones & Bartlett Learning,maltose LLC and lactose, whereas© bothJones anomeric & Bartlett carbons Learning, are involved LLC in NOT FOR SALE OR DISTRIBUTIONthe glycosidic bonds in sucroseNOT and FOR trehalose. SALE OR DISTRIBUTION

OH OH

NOT FOR SALE OR DISTRIBUTION OH NOT FOR SALE OROH DISTRIBUTION HO OH H OH

OH OH © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC H2O NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION OH OH

O O

OH OH Maltose © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning,(α form) LLC NOT FOR SALE OR DISTRIBUTIONHO ONOT FOR SALEOH OR DISTRIBUTION OH OH

OH OH © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC O NOT FOR SALE OR DISTRIBUTION NOT FORO SALE OR OHDISTRIBUTION Maltose C OH OH (open-chain form) HO O

OH OH © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION OH OH

O O OH OH OH Maltose © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, form) LLC HO O (β NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION OH OH FIGURE 4.13 Maltose as a Reducing Sugar. Maltose consists of a glucose bearing an alpha anomeric carbon locked to a second glucose molecule. The second glucose molecule is in equilibrium with an open-chain form © Jones & Bartlett Learning, LLC the alpha form,© andJones the beta & Bartlett form. The Learning, presence of theLLC carbonyl makes the NOT FOR SALE OR DISTRIBUTION entire maltoseNOT molecule FOR a reducingSALE OR sugar. DISTRIBUTION

50 Chapter 4 CARBOHYDRATES 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALEWhen OR just DISTRIBUTION one anomeric carbon is involved in glycosideNOT FOR formation, SALE OR DISTRIBUTION as in the maltose and lactose, a free anomeric carbon remains in BOX 4.2: Word Origins equilibrium with an open-chain form (see Figure 4.13 for maltose). Because at least a small amount of this open-chain form exists in Reducing solution, its carbonyl group can reduce certain metal ions in diagnos- © Jones & Bartlett Learning, LLC When a word© Jones with rich &meanings Bartlett such Learning,as reduc- LLC tic tests. Any saccharide that has at least one free anomeric carbon NOT FOR SALE OR DISTRIBUTION ing is appliedNOT to sugar FOR chemistry, SALE its OR interpretation DISTRIBUTION (i.e., an anomeric carbon not involved in a glycosidic bond) is therefore may be obscured. There are distinct sociological, called a reducing sugar. Maltose and lactose are reducing sugars. By mathematical, biological, and chemical definitions contrast, sucrose and trehalose are nonreducing sugars because they for this word. In the everyday sense, the word origi- have no free anomeric carbon atoms. To better understand the chemical nally meant to bring back, or to restore, an original condition. A later use was related to conquest, and meaning© Jones of the &word Bartlett reducing, Learning, see Box 4.LLC2. © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FORsubsequently, SALE a OR general DISTRIBUTION sociological meaning of lowering.

Mathematically, the term refers to the factor-label Polysaccharides method of manipulating units algebraically in a 4.4 separate way from the numbers they label. In biol- © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC When more than two sugars are linked via glycosidic bonds, they are ogy, meiosis involves a reductive division, in which NOT FOR SALE OR DISTRIBUTION NOT FOR SALE ORthe DISTRIBUTION number of chromosomes is halved. In chemistry, said to be either oligosaccharides (meaning “a few”) or polysaccharides reduction is the decrease in oxidation number for an (meaning “many”). The distinction is inexact; some consider chains of atom. A compound is reduced if it gains electrons, up to a dozen or so linked sugars to be oligosaccharides. Commonly, so the term reduction is somewhat misleading as polysaccharides have thousands of monosaccharide residues bound © Jones & Bartlett Learning, LLC a description© Jones of the chemical & Bartlett process. Learning,Reducing LLC together. Such molecules have extremely large molecular weights, sugars transfer electrons from the carbonyl group which leads to propertiesNOT distinctFOR SALE from smallerOR DISTRIBUTION molecules. In general, to copper NOTor silver FOR ions. InSALE most cases, OR aDISTRIBUTION further large molecules that are constructed from small, repeating units are electron transfer is present to produce a color reac- called polymers. The polysaccharides are our first example of biological tion, confirming the result visually. polymers; the other two major classes are proteins and nucleic acids. None of these definitions describes the dieter’s While© Joneslipids can & Bartlettform large Learning, aggregates LLC with new properties, they© Jones dream & molecule:Bartlett a trulyLearning, reducing sugar. LLC Still, there are notNOT biological FOR SALE polymers, OR DISTRIBUTION because they consist of noncovalentlyNOT FORis a long SALE history ORof artificial DISTRIBUTION sweeteners. Sucralose, associated small molecules. Nonbiological polymers, such as nylon, for example, is a modern artificial sweetener made were discovered and studied at the same time as biological polymers. by chlorinating sucrose (Figure B4.2). As a Nonbiological and biological polymers share some properties, including result, sucralose can attach itself to the taste recep- the methods used for their analysis. tors (the sweet receptors in cells of the tongue), © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning,but is metabolically LLC inert. Thus, sucralose provides NOT FOR SALE OR DISTRIBUTION NOT FOR SALE ORthe DISTRIBUTION sweetness of sucrose, but none of the calories.

Sucrose itself is the standard of sweeteners for both artificial and natural sugars. The measurement scale OH OH is less objective than others, because it requires O © Jones & Bartlett Learning,O LLC human tasters.© Jones This is especially & Bartlett troublesome Learning, for the LLC Cl discovery of new sweeteners that, unlike sucralose, OH NOT FOR SALE OROH DISTRIBUTION NOT FOR SALE OR DISTRIBUTION may bear no structural similarity at all to sugars, HO making it impossible to predict in advance whether O O OH OH a compound is a potential candidate. Typically, a sweetener is discovered by accident; someone O OH O © Jones & Bartlett Learning, LLC © Jonesworking & Bartlett with a chemical Learning, product has LLC actually tasted it (and survived!). NOT FORCl SALEHO OR DISTRIBUTION HO NOT FOR SALE OR DISTRIBUTION Cl CH2OH

OH OH Sucralose Sucrose © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC FIGURE B4.2 Sucralose and Sucrose. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

chapter 4 CARBOHYDRATES 51 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OROH DISTRIBUTIONOH OH NOTOH FOR SALE OHOR DISTRIBUTIONOH OOO O O O OH OH OH OH OH OH HO OOOOO OH OH OH OH OH OH OH © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Non-reducing end Reducing end NOT FOR SALE OR DISTRIBUTIONOr… NOT FOR SALE OR DISTRIBUTION

O O O O O

O O O O O FIGURE 4.14© Amylose Jones Has & BartlettDistinct Ends. Learning, The straight-chain LLC glucose polymer amylose© Jones has a1 &→ 4Bartlett bonds. At Learning,the left-end residue, LLC the anomeric carbon is engaged in a glycosidic bond, and thus is nonreducing. At the right end residue, the anomeric carbon is free and, thusNOT is reducing.FOR SALE All polysaccharides OR DISTRIBUTION have these distinctive ends. NOT FOR SALE OR DISTRIBUTION

Linear Polysaccharides © Jones & Bartlett Learning, LLC Amylose is a© biological Jones &polysaccharide Bartlett Learning, composed LLC of glucose molecules NOT FOR SALE OR DISTRIBUTION linked via a1NOT→4 glycosidic FOR SALE bonds OR (Figure DISTRIBUTION 4.14). Like all linear polymers, the amylose chains have distinctive ends, called the reducing end and the nonreducing end. This property of dissimilar ends also applies to disaccharides. Maltose also has a reducing end and a nonreducing end, © Jones & Bartlettalbeit Learning, a chain of justLLC two monosaccharide units.© Jones All unbranched & Bartlett poly Learning,- LLC NOT FOR SALEsaccharides OR DISTRIBUTION have exactly one reducing end NOTand one FOR nonreducing SALE OR end. DISTRIBUTION In solution, amylose forms hydrogen bonds between water molecules and the free hydroxyl groups at positions 2, 3, and 6. This makes it an extended polymer with considerable flexibility. Cellulose, another linear polymer of glucose, has b1→4 linkages, © Jones & Bartlett Learning,and LLC assumes the very regular© Jones three-dimensional & Bartlett Learning,solution structure LLC NOT FOR SALE OR DISTRIBUTIONshown in Figure 4.15. TheNOT specific FOR arrangement SALE OR DISTRIBUTIONresults from the

H H O O H H H CH © Jones & Bartlett Learning, LLC ©O JonesH &CH 2Bartlett Learning,H O H LLC 2 H H H HHH O H O NOT FOR SALE OR DISTRIBUTION O NOTO FOR SALEH ORO DISTRIBUTIONO H H OH HO H O O O O H O H H H H H H O H H O H H CH H CH2 H 2 H O O O O H H H H H CH O H CH2 H O H 2 H H H © Jones & Bartlett Learning,HHH LLC O H © Jones & BartlettO Learning, LLC O O H O O H NOT FOR SALE OR DISTRIBUTION HNOT FOR SALEOH OR DISTRIBUTION HO H O O O O H O H H H H H H O H H O H CH H CH2 H H 2 H O O O O H H H H H CH O H CH2 H O H 2 H H H HHH O H O © Jones & Bartlett Learning, LLC O O © HJones &O Bartlett OLearning,H LLC H OH NOT FOR SALE OR DISTRIBUTIONHO H O NOT FORO SALE OR DISTRIBUTIONO O H O H H H H H H O H H O H CH CH2 H 2 H O O H H FIGURE 4.15 Cellulose. Cellulose does not interact with water because © Jones & Bartlett Learning, LLC all of its hydroxyl© Jones groups &are Bartlett engaged inLearning, intracellular LLC hydrogen bonding. NOT FOR SALE OR DISTRIBUTION As a result, celluloseNOT FOR is completely SALE insolubleOR DISTRIBUTION in water.

52 Chapter 4 CARBOHYDRATES 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORglycosidic SALE OR bond DISTRIBUTION being placed above the plane of theNOT glucosyl FOR residue. SALE OR DISTRIBUTION All of the hydroxyl groups in the chain interior are engaged in hydrogen bonds with each other. The resulting intramolecular hydrogen bonding gives the molecule enormous internal strength, but it also renders cellulose unable to bind to water. Cellulose, therefore, is entirely insoluble © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC in water, despite the existence of multiple hydroxyl groups (Box 4.3). Cellulose is the most NOTabundant FOR molecule SALE inOR the DISTRIBUTION world, principally found NOT FOR SALE OR DISTRIBUTION in plant cell walls; it is the major component of wood. An important reason for using polysaccharides as energy storage molecules in animals has to do with osmosis. Osmolarity depends only on the© number,Jones &rather Bartlett than Learning,the size (or LLCother qualities) of molecules.© Jones & Bartlett Learning, LLC Thus,NOT having FOR multiple SALE glucoseOR DISTRIBUTION molecules covalently linked greatlyNOT FOR SALE OR DISTRIBUTION reduces the osmolarity within the cell compared to individual molecules, thereby minimizing osmotic pressure while maintaining a virtual glucose reservoir within the cell. This is critically important for animal © Jones &cells, Bartlett which Learning,must maintain LLC the same osmolarity on© either Jones side & ofBartlett the Learning, LLC plasma membrane. By contrast, plants simply have a cell wall—for NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION which cellulose is a key structural component—allowing plant cells to maintain very high internal osmotic pressures without bursting.

Branched Polysaccharides © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Amylopectin is a branchedNOT FOR polysaccharide SALE OR DISTRIBUTIONthat occurs in plants. In NOT FOR SALE OR DISTRIBUTION addition to a1→4 linkages, amylopectin also has a1→6 linkages commonly called branch points. Figure 4.16 shows how a single a1→6 glycosidic bond creates a branch in the overall structure. Branched© Jones polysaccharides & Bartlett Learning,have a more LLC compact three-dimensional© Jones & Bartlett Learning, LLC structure than linear chains. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

BOX 4.3: Irony of Intramolecular Hydrogen Bonds © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Hydrogen bonding is a key feature that makes certain compounds soluble in NOT FOR SALEwater. However, OR DISTRIBUTION when the groups responsible for hydrogenNOT bonding FOR are linkedSALE OR DISTRIBUTION to a group other than water, they lose their solubility. This commonly occurs when hydrogen bonding exists within the same molecule; that is, the hydrogen bonding is intramolecular. Cellulose, a polymer of glucose found in plants, is a perfect example of a compound© Jones that & is Bartlett insoluble in Learning, water due to intramolecularLLC © Jones & Bartlett Learning, LLC hydrogen bonds. TheseNOT kinds FOR of interactions SALE OR exist DISTRIBUTION in all biological polymers, NOT FOR SALE OR DISTRIBUTION however, including nucleic acids and proteins.

A practical application of this property is the development of synthetic molecules called methylcelluloses. These are formed in the laboratory by creating© Jones methyl & esters Bartlett with some Learning, of the hydroxyl LLC groups of cellulose. Partial© Jones & Bartlett Learning, LLC methylationNOT FOR prevents SALE the remaining OR DISTRIBUTION free hydroxyl groups from forming internalNOT FOR SALE OR DISTRIBUTION hydrogen bonds, creating new polymers whose partial solubility in water can be controlled. These polymers can be used as solvents for lipid-soluble drugs. The glucose molecules in cellulose are connected by beta linkages, © Jones & forBartlett which humans Learning, have no LLC enzymes to break down, so© methylcellulose Jones & Bartlett is Learning, LLC NOT FOR SALEbiologically OR inert. DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

chapter 4 CARBOHYDRATES 53 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC O O NOT FOR SALE OR DISTRIBUTION NOT FOR SALE1 OR DISTRIBUTION O O α1 6 bond 6 O O O O O

O O O O O © Jones & BartlettFIGURE Learning, 4.16 A Polysaccharide LLC Branch Point. The© Jones a1→6 bond, & Bartlett found in Learning, LLC NOT FOR SALEglycogen OR DISTRIBUTION and amylopectin, creates a branch pointNOT in FORthe polysaccharide SALE OR DISTRIBUTION structure. With one branch point, there are now two nonreducing ends and still one reducing end.

© Jones & Bartlett Learning, LLCStarch is a mixture of amylose© Jones and amylopectin & Bartlett that Learning, occurs in plants.LLC NOT FOR SALE OR DISTRIBUTIONDifferent plants have variousNOT proportions FOR SALE of the OR two DISTRIBUTION polysaccharides, with different polymer lengths and different degrees of branching accounting for the distinctive qualities of corn starch, potato starch, and wheat starch (flour). © Jones & Bartlett Learning, LLC A purely© branched Jones &polysaccharide Bartlett Learning, is glycogen LLC, the major form of carbohydrate storage in animal cells. Molecules of glycogen are more NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION branched than amylopectin and are much larger, having hundreds of thousands of glucose residues. While glycogen exists in a variety of animal cells, it is found in large amounts in just two: liver and muscle. Liver stores glycogen in the fed state and releases glucose © Jones & Bartlettunits Learning, from it to the LLC blood during times of fasting.© Jones By contrast, & Bartlett muscle Learning, LLC NOT FOR SALEtakes OR DISTRIBUTIONup blood glucose and uses the glucoseNOT residues FOR of SALE glycogen OR for DISTRIBUTION its own metabolism during active contraction. Thus, the liver’s role in glucose balance is altruistic, providing for the entire body, whereas the muscle’s role is selfish, being used only for muscle metabolism. Most of the glycogen molecules in the human body are found in © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC muscle, which has about 1% of its weight as glycogen. Liver can NOT FOR SALE OR DISTRIBUTIONhave up to 10% of its weightNOT as FOR glycogen SALE (during OR DISTRIBUTION the fed state), but represents less of the total body glycogen due to its relatively small total mass.

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION 4.5 CarbohydrateNOT FOR SALE Derivatives OR DISTRIBUTION A large number of molecules have many of the qualities of carbohydrates, because they are metabolically derived from them. We will consider © Jones & Bartletttwo Learning,categories of LLC such derivatives: simple ©modifications Jones & Bartlett and substi Learning,- LLC NOT FOR SALEtuted OR DISTRIBUTIONcarbohydrates. The simple modificationsNOT consist FOR of SALE only slightlyOR DISTRIBUTION modified monosaccharides and polysaccharides. In the more heavily substituted carbohydrates, the sugar portion is no longer the dominant chemical property. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONSimple Modifications NOT FOR SALE OR DISTRIBUTION The modification of hydroxyl groups by a phosphate ester occurs in many of the metabolic intermediates we will encounter in later chapters. For example, glucose-6-P (the phosphate group is abbreviated as P)

54 Chapter 4 CARBOHYDRATES 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORtwo SALE phosphate OR DISTRIBUTION esters (Figure 4.17). Another simpleNOT modification FOR SALE is OR DISTRIBUTIONO to change the oxidation state of one of the carbons. Reduction of the O P O– carbonyl carbon results in a sugar alcohol, or polyalcohol, such as – glycerol (Figure 4.18). Glycerol is a product of fat breakdown and a O major additive in prepared foods and drugs. Conversely, oxidation of the O © Jones & Bartlett Learning, LLC © Jones & BartlettOH Learning, LLC carbonyl group produces a sugar acid, such as glyceric acid. Oxidation NOT FOR SALE OR DISTRIBUTION NOT FOROH SALE OR DISTRIBUTION can also occur at other carbons, leaving the carbonyl group intact, as in HO glucuronic acid. Glucuronic acid is compared to the carbonyl-oxidized OH gluconic acid in Figure 4.19. Note that gluconic acid cannot exist in a ring form. Glucose-6-P Replacing© Jones an& Bartlettoxygen atom Learning, with a nitrogenLLC atom forms another© Jones & BartlettO Learning, LLC derivative,NOT FORexemplified SALE by OR glucosamine DISTRIBUTION (Figure 4.20), which is foundNOT FOR SALE OR DISTRIBUTION – as a subunit of secreted proteins and in connective tissue. Derivatives O P O O in which one of the hydroxyl groups is replaced with a hydrogen atom, O– OH

as in deoxyribose (Figure 4.20) are called deoxy sugars. HO © Jones & BartlettPolysaccharides Learning, can LLCalso be modified to produce© Jonesderivatives & Bartlett with Learning, LLC O altered properties. For example, the molecule agarose (found in NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION O P O– certain seaweeds) has a repeating d-galactosyl unit linked with a b1→4 OH glycosidic bond to an l-galactosyl residue that is modified by having O– an additional internal bridge oxygen between carbons 3 and 6 and a Fructose-1,6-bis-P2 sulfate group esterified to carbon 2 (Figure 4.21). Agarose is a linear FIGURE 4.17 Phosphorylated Sugars. molecule of this repeating© Jones unit, & Bartlettalthough Learning,not all of its LLC l-galactosyl © Jones & Bartlett Learning, LLC groups are sulfated.NOT A similar FOR polysaccharide SALE OR DISTRIBUTION is agaropectin, which NOT FOR SALE OR DISTRIBUTION has branch points. Together, the mixture of agarose and agaropectin is known as agar. O C © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Substituted Carbohydrates OHC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Nucleotides, lipopolysaccharides, and proteoglycans all contain sugar OHC molecules, but they are so heavily modified by other groups that their Glyceraldehyde chemical features greatly diverge from less substituted sugars. Reduction Oxidation Nucleotides are modified sugar molecules that contain a nitrogenous © Jones &base Bartlett and at leastLearning, one phosphate LLC ester. The bases are© either Jones pyrimidines & Bartlett Learning, LLC OHC COOH NOT FORor SALE purines, OR as DISTRIBUTION shown in Figure 4.22. Nucleosides NOThave FORbases SALEjoined OR DISTRIBUTION to either a ribose or a deoxyribose sugar in an N-glycosidic link, as OHC OHC shown in Figure 4.23. Note that the nitrogen attached to the sugar is the 1-position of the pyrimidines but the 9-position of the purines. OHC OHC The sugar portion is© further Jones substituted & Bartlett in Learning, nucleotides: LLC a phosphate Glycerol© Jones & BartlettGlyceric acidLearning, LLC is esterified to one ofNOT the FOR available SALE hydroxyl OR DISTRIBUTION groups. These can be FIGURE 4.18NOT Redox FOR Derivatives SALE ofOR Sugar. DISTRIBUTION monophosphates or chains of phosphates. Figure 4.24 shows the three common nucleotides known as AMP, ADP, and ATP. Nucleotides are key energy transfer molecules that are widely used in metabolic reactions in cells. Additionally, nucleotides are joined © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC together to form the polymers DNA and RNA, where the sugar componentNOT FOR of DNA SALE is deoxyribose OR DISTRIBUTION and the sugar component of RNANOT FOR SALE OR DISTRIBUTION is ribose. DNA exists as two strands noncovalently linked by hydrogen bonds between the bases (Figure 4.25). The sugar component of DNA (i.e., deoxyribose) has no remaining free hydroxyl groups. The © Jones &2′ positionBartlett is Learning, substituted byLLC a hydrogen atom and all ©others Jones are involved& Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

chapter 4 CARBOHYDRATES 55 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC O O – NOT FOR SALE OR DISTRIBUTION NOTOH FOR SALE(β1 OR 4) DISTRIBUTION O S 1C 6 3 2 O– OH HO 5 O O 6 OHC O O O 4 O 1 1 4 HO C 6 OH © Jones & Bartlett Learning, LLC © Jones & BartlettO Learning, LLC O NOT FOR SALEOHC OR DISTRIBUTION3 2 NOT FOR SALE OR DISTRIBUTION HO OH 5 OHC OH OH D-Galactosyl 3,6-Anhydro- OHC Glucose galactosyl-3-sulfate © Jones & Bartlett Learning,F IGURELLC 4.21 Agarose. The repeating© Jones unit of& theBartlett polysaccharide Learning, agarose, LLC a linear modified polysaccharide. The two residues shown are a galactosyl C6 oxidation NOT FOR SALEC1 oxidation OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION unit and a modified galactose in a b1→4 linkage.

in the linkages that bind the nucleotides together. RNA, unlike DNA, COOH 1 © Jones6 & Bartlett Learning, LLC COOH is usually a single-stranded© Jones & Bartlett polymer Learning, (Figure 4.26 LLC). O DNA provides a template for two cellular processes. First, the NOT FOR SALE OR DISTRIBUTION OHC NOT FOR SALE OR DISTRIBUTION OH molecule can duplicate itself in preparation for cell division, an activity HO C known as replication. Second, small regions of DNA can serve as a HO OH template for messenger RNA (mRNA) formation, an activity known as OHC OH transcription. In turn, mRNA provides a template for protein synthesis © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Glucuronic acid OHC (translation). These processes are critical to the formation of new NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION OHC cells or of new expression for cells. Sugars form conjugates with other biological molecules. For Gluconic acid example, some phospholipids are sugar-lipid derivatives such as FIGURE 4.19 Different Oxidized Glucose phosphatidylglycerol and phosphatidylinositol (Figure 4.27). Sugar– Molecules. Oxidizing© Jones glucose & Bartlett at the anomeric Learning, protein LLC conjugates (called glycoproteins© Jones & )Bartlett are usually Learning, divided into LLC two carbon forms gluconic acid, which can no longer form NOTa ring FORor become SALE polymerized. OR DISTRIBUTION classes: O-linked and N-linkedNOT (Figure FOR SALE4.28a and OR b). DISTRIBUTION In the O-linked If any other carbon in glucose is oxidized, example, a glycosidic bond is formed between the sugar (the modified yielding a compound such as glucuronic acid, sugar N-acetylgalactosamine is shown) and a hydroxyl group from a it can still form a glycosidic bond and thus be part of a polysaccharide.

© Jones & Bartlett Learning, LLC © Jones & BartlettO Learning,NH2 LLC O 4 4 4 4 NOT FOR SALE OR DISTRIBUTION 3 NOT FOR 3SALE CHOR DISTRIBUTION3 3 5 3 5 N HN 5 N HN 5 2 2 2 2 6 6 6 6 OH 1 N O 1 N O 1 N O 1 N H H H O OH O Thymine (T) Cytosine (C) Uracil (U) OH © Jones & BartlettOH Learning, LLC © Jones & Bartlett Learning, LLC OH NOT FOR SALE OR DISTRIBUTION Pyrimidine PyrimidineNOT bases FOR SALE OR DISTRIBUTION HO

NH 2 OH NH2 O 6 6 Glucosamine 2-Deoxyribose 7 6 7 7 5 N 5 N 5 N © Jones & Bartlett Learning, LLCN 1 N© Jones & BartlettHN Learning, LLC FIGURE 4.20 Sugar Derivatives Replacing 1 1 8 8 8 Hydroxyl Groups.NOT FOR SALE OR DISTRIBUTION2 2 NOT FOR SALE2 OR DISTRIBUTION 4 N 9 4 N 9 4 N 9 3 N 3 N H N 3 N H H 2 H

Adenine (A) Guanine (G) Purine Purine bases © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION FIGURE 4.22 NOTPurines FOR and Pyrimidines.SALE OR DISTRIBUTION

56 Chapter 4 CARBOHYDRATES 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC O NOT FORprotein, SALE hereOR contributedDISTRIBUTION from the side group of anNOT amino FOR acid SALEcalled OR DISTRIBUTIONNH2 6 4 7 serine. The N-linked example in Figure 4.28b shows an N-glycosidic 3 5 N N 5 HN 1 bond, similar to those found in nucleotides. Here, the nitrogen is 8 2 2 contributed by the side group of an amino acid called asparagine. 6 9 O 4 N An additional protein–sugar conjugate arises when an amine from 1 N H2N 3 N © Jones & Bartlett Learning, LLC 5 CH OH © Jones & Bartlett5 CH OH Learning, LLC a lysine side chain in hemoglobin reacts with glucose, followed by 2 2 NOT FOR SALE OR DISTRIBUTION O NOT FOR SALE ORO DISTRIBUTION rearrangement to the stable ketone shown (Figure 4.28c). This relatively 4 1 4 1 slow reaction produces a form of hemoglobin abbreviated as HbA1C. Measuring HbA levels provides a measure of the average blood 3 2 3 2 1C OH OH OH glucose over a period of weeks. HbA , therefore, is of considerable 1C Cytisine Deoxy-guanosine importance© Jones in monitoring& Bartlett diabetics. Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FFORIGURE SALE 4.23 Nucleosides. OR DISTRIBUTION A base from those shown in Figure 4.22 is attached to a ribose sugar or a deoxyribose sugar. A large number Summary of other combinations are possible, with two exceptions: uracil is not found attached Sugars have an empirical formula of CH2O, with multiple hydroxyl to deoxyribose, and thymine is not found © Jones &groups Bartlett and Learning,one carbonyl LLC group in the simple sugars.© Jones The smallest& Bartlett attached Learning, to ribose. LLC NOT FORmonosaccharides SALE OR DISTRIBUTION are the trioses glyceraldehyde and NOTdihydroxyacetone. FOR SALE OR DISTRIBUTION

NH2 N N “Ribbon” ladder Sugar- Hydrogen bond

© Jones & Bartlett Learning,representation LLC phosphate © Jones & Bartlett Learning, LLC of DNA helix backbone O – – – H O O NOTO FOR SALEN ORN DISTRIBUTION NOT FOR SALE OR DISTRIBUTION O H3C H N N H 3′ O P O P OOP CH2

O O H T N H N A N O

O O O 5′ O 5′

N N O O H O —

AMP O N O

H C N H N G 5′ 5′ O O N N

ADP H O —

FIGURE 4.24 AMP, ADP, and ATP. A nucleotide H O is a phosphorylated nucleoside. The three O N N O

O 5′ examples shown here are the most common 5′ N H N O N A T H nucleotide forms of adenine, used in energy

H N HN H O CH3 O O NOT FOR SALE OR DISTRIBUTION NOTH FOR SALE OR DISTRIBUTION —O P O 3′ N H O

O N N O

O 5′ 5′ O N G N H N C H

FIGURE 4.25 DNA. The two strands of the double-stranded DNA molecule © Jones & Bartlett Learning, LLC are linked© Jones by hydrogen & Bartlett bonding. Learning, Within each LLC strand, the sugars are NOT FOR SALE OR DISTRIBUTION covalentlyNOT linked FOR via SALE phosphate OR diesterDISTRIBUTION bonds.

chapter 4 CARBOHYDRATES 57 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC O NOT FOR SALE OR DISTRIBUTION O NOT FOR SALE OR DISTRIBUTION H3C O CH2 O C O CH2 O C H U N H O 5 O O N CH O C CH O C 3 © JonesO & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC OH OH O O NOTH FOR SALE OR DISTRIBUTION NOTO FOR SALE OR DISTRIBUTION — O P O H N H CH2 OOP C CH2 OOP OH O O– COH H C N O– 5 O N COH OH OH © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 3 O Phosphatidyglycerol Phosphatidylinositol NOTO FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION FIGURE 4.27 Phosphatidylglycerol and Phosphatidylinositol. —O P O H O N O 5 N There are two stereochemical forms of glyceraldehyde because it has N A © Jones & Bartlett Learning, LLC a chiral center.© Jones These are& Bartlettdenoted dLearning, and l, but LLC biological sugars are NOT FOR SALE3 OR DISTRIBUTIONH N HN NOT FOR SALE OR DISTRIBUTION O overwhelmingly in the d form. Sugars containing more carbon atoms H have correspondingly larger numbers of stereoisomers, which are —O P O N identified by assigning unique names. For example, one six-carbon O N sugar is glucose; another, differing in configuration at the 4-carbon, is 5 O N © JonesG N & Bartlettgalactose, Learning, equivalently LLC expressed as the 4-epimer© Jones of glucose. & Bartlett All sugars Learning, LLC NOT FOR SALEhaving OR DISTRIBUTION at least five carbon atoms form ringsNOT in a FOR reaction SALE between OR DISTRIBUTION a 3 H N O carbonyl group and a hydroxyl group. The formation of rings produces O a new chiral center, because a new hydroxyl group emerges from the

FIGURE 4.26© RNA. Jones Like & DNA, Bartlett the sugar Learning, LLC(a) OH © Jones & Bartlett(c) Learning, LLC portion of RNA binds the chain together, using NOT FOR SALE OR DISTRIBUTION NOT FOR SALE ORC DISTRIBUTIONNLys Hb phosphate diester bonds as shown. The purine O HO Ser and pyrimidine bases also are attached to the OH C O sugars of RNA like those of DNA. Unlike DNA, HO C the RNA molecule is typically a single chain. O Protein C OH © Jones & Bartlett Learning, LLC © JonesNC & BartlettCH3 Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTIONC OH O N-acetyl-glucosamine-O linked COH

HbA glycosylated hemoglobin (b) OH © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC O NOT FOR SALE OR DISTRIBUTIONHO N NOT FOR SALE OR DISTRIBUTION OH Asn

Protein NC CH3 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION O NOT FOR SALE OR DISTRIBUTION N-acetyl-glucosamine-N linked FIGURE 4.28 Sugar-Modified Proteins. The most common modifications are (a) O-linked and (b) N-linked polysaccharides; these are glycosidic and N-glycosidic bonds, respectively. (c) A nonenzymatic reaction of glucose © Jones & Bartlett Learning, LLC with hemoglobin© Jones produces & aBartlett specially modifiedLearning, glycosylated LLC hemoglobin. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

58 Chapter 4 CARBOHYDRATES 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALEBOX 4.4: OR Medical DISTRIBUTION Connections: Sugars and DigestionNOT FOR SALE OR DISTRIBUTION Sugars are normally absorbed by the small intestine. If appreciable amounts are not removed by the time they reach the large intestine, they are metabolized there by the resident© Jones bacteria. & The Bartlett bacterial Learning, end products LLCinclude gases © Jones & Bartlett Learning, LLC which cause distensionNOT of the FOR colon, SALE bloating, OR and DISTRIBUTIONpain. Two of the most com- NOT FOR SALE OR DISTRIBUTION mon causes of this bloating are lactose intolerance and raffinose. Lactose intolerance is a common genetic deficiency of lactase, an enzyme that breaks down the sugar lactose. Lactase is present in abundance in infants and less so in adults. Because lactose is only present in milk and milk products, and milk is a© normal Jones component & Bartlett of the Learning,diet only in infancy LLC in all animals but humans,© Jones & Bartlett Learning, LLC lactoseNOT intolerance FOR SALE is strictly OR a humanDISTRIBUTION problem. NOT FOR SALE OR DISTRIBUTION

A common intestinal disturbance is caused by the presence of raffinose, a sugar found in foods such as cabbage and beans. Raffinose is poorly digested due to the presence of the galactose-a1→6-glucose bond in the first two © Jones & sugarBartlett moieties Learning, of the trisaccharide. LLC As a result, it is also© metabolized Jones & in Bartlett the Learning, LLC NOT FOR SALElarge intestine, OR DISTRIBUTION with attendant gas production. However, dueNOT to the FOR far smaller SALE OR DISTRIBUTION amounts of raffinose in those foods, the clinical symptoms of raffinose digestion are less severe than those in lactose intolerance.

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION carbonyl group. The carbon at this locus is called the anomeric carbon and is always involved in joining sugar moieties together, either as disaccharides like sucrose and maltose, or in polysaccharides, such as glycogen and cellulose. The link between sugars is called a glycosidic bond,© and Jones it locks & Bartlettthe position Learning, of the anomeric LLC hydroxyl into two sepa© Jones- & Bartlett Learning, LLC rate NOTstereochemical FOR SALE forms OR (a DISTRIBUTIONand b). The three-dimensional structureNOT FOR SALE OR DISTRIBUTION that results from this distinctive orientation is the difference between glycogen, the water-soluble storage carbohydrate in animals, and cellulose, the water-insoluble storage carbohydrate that is abundant © Jones &in Bartlettplants. Any Learning, sugar that LLC contains an anomeric carbon© Jones that & isBartlett not Learning, LLC connected via a glycosidic bond can equilibrate with the open-chain NOT FORform. SALE Because OR DISTRIBUTION it can react with a test solution containingNOT FOR an ion SALE that OR DISTRIBUTION can be reduced to produce a color reaction, it is called a reducing sugar. This describes all monosaccharides and polysaccharides and some disaccharides such as maltose. Both of the anomeric carbons of the bound sugars forming© Jones sucrose & Bartlett are engaged Learning, in a glycosidic LLC bond, © Jones & Bartlett Learning, LLC making this disaccharideNOT aFOR nonreducing SALE OR sugar. DISTRIBUTION Polysaccharides have NOT FOR SALE OR DISTRIBUTION at least one end—more if there are branches—in which the anomeric carbon is engaged in a glycosidic bond. This is called a nonreducing end. A myriad of carbohydrate derivatives exist in biology, both of the simple© Jonesmonosaccharides & Bartlett (such Learning, as phosphorylated LLC sugars and deoxy© Jones & Bartlett Learning, LLC sugars) and the polysaccharides (such as the sulfated polymer agarose). NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION More elaborate substitutions produce molecules where the properties of the sugar itself are lost, and the sugar merely becomes a connecting molecule, such as the role deoxyribose plays in the structure of DNA. Finally, sugars form conjugates with other biological molecules, as in © Jones &lipopolysaccharides Bartlett Learning, and LLCproteoglycans. © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

chapter 4 CARBOHYDRATES 59 2ND PAGES © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION Key TermsNOT FOR SALE OR DISTRIBUTION

agar galactose oligosaccharides agaropectin glycogen polymers agarose glycosidic bond polysaccharides © Jones & Bartlettaldoses Learning, LLC Fischer projection © Jonespolarimeter & Bartlett Learning, LLC alpha (form) Haworth projections raffinose NOT FOR SALEanomeric OR DISTRIBUTION carbon hemiacetals NOTreducing FOR SALEend OR DISTRIBUTION beta (form) hemiketals reducing sugar branch points ketoses replication cellulose lactose intolerance sugar acid chiral methylcelluloses transcription © Jones & Bartlett Learning,disaccharides LLC nonreducing© Jones end & Bartletttranslation Learning, LLC enantiomers nonreducing sugars trehalose NOT FOR SALE OR DISTRIBUTIONepimers nucleotidesNOT FOR SALE ORtriose DISTRIBUTION

Review Questions © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 1. Raffinose is a sugar that, upon hydrolysis of its glycosidic bonds, yields galactose, NOT FOR SALE OR DISTRIBUTION glucose, andNOT fructose. FOR The SALEgalactose–glucose OR DISTRIBUTION bond is an a1→6 linkage, and the trisaccharide is a nonreducing sugar. Draw the structure of raffinose. 2. In the DNA structure, the sugar is completely modified. List each modification and identify an analogous, simpler substitution that exists in another sugar molecule. What sugar properties remain in the DNA molecule? © Jones & Bartlett3. Glucose Learning, in solution LLC has two ring forms and one© open-chain Jones &form. Bartlett How many Learning, LLC NOT FOR SALE ORstructures DISTRIBUTION exist in equilibrium for a polysaccharideNOT of glucose FOR thatSALE has multipleOR DISTRIBUTION a1→4 bonds and three a1→6 bonds? 4. Reducing sugars are a mixture of alpha and beta forms. Why does one predominate over another in different sugars? 5. Related to the previous question, suppose you have equal concentrations of glucose and fructose at room temperature. In both cases, beta-ring forms predominate, © Jones & Bartlett Learning, LLCbut with different percentages.© InJones each case, & Bartletthowever, when Learning, a reducing LLC sugar NOT FOR SALE OR DISTRIBUTIONmeasurement is made, the sameNOT amount FOR of indicator SALE ion OR is reducedDISTRIBUTION in each case. Moreover, the amount of directly reacting species for the indicator ion is far less than 1% of the total forms. Explain these findings. 6. One indication of the distinction in physical properties between simple sugars (like monosaccharides and disaccharides) and polysaccharides is their observed behavior in solution. For example, only starch can form a paste in water. Speculate © Jones & Bartlett Learning, LLC on how that ©can Jones be explained & Bartlett from the structuralLearning, differences LLC between these types NOT FOR SALE OR DISTRIBUTION of molecules.NOT FOR SALE OR DISTRIBUTION

References © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 1. DeMan, J. M. Principles of Food Chemistry; Springer Publishing: New York, 1999, NOT FOR SALE ORChapter DISTRIBUTION 4, pp.163–208. NOT FOR SALE OR DISTRIBUTION A treatise on the chemistry of food, the chapter on carbohydrates includes many of the biochemical properties of sugars in more extensive detail than is described in the present text. 2. Semenza, G.; Auricchio, S. Small-Intestinal Disaccharidases. In The Metabolic Basis © Jones & Bartlett Learning, LLCof Inherited Disease; Scriver, C.© R.; Jones Beaudet, & A. Bartlett L.; Sly, W. Learning,S., Eds.; McGraw-Hill: LLC NOT FOR SALE OR DISTRIBUTIONNew York, 1995, Chapter 22, NOTpp. 4451–4480. FOR SALE OR DISTRIBUTION This is an authoritative reference work on inherited diseases that affect metabolic pathways. In this chapter, the inborn errors associated with lactose and other disaccharides are described in detail. 3. Sinnott, M. L. Carbohydrate Chemistry and Biochemistry: Structure and Mecha- nism; Royal Society of Chemistry: Cambridge, UK, 2007, p. 748. © Jones & Bartlett Learning, LLC This is a more© chemicallyJones & oriented Bartlett description Learning, of carbohydrates. LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION