CHAPTER 07 Carbohydrates and the Glycoconjugates of Cell Surfaces

7-1 How Are Carbohydrates Named?

1. molecular formula (CH2O)n, are hydrates of carbon
2. monosaccharides：cannot be broken down into smaller sugars under mild conditions
3. oligosaccharides：from two to ten simple sugar residues
4. polysaccharides：polymers of the simple sugars and their derivatives
7-2 What Are the Structure and Chemistry of Monosaccharides?
 Monosaccharides Are Classified as Aldoses and Ketoses
1. The simplest monosaccharides are water soluble
2. Aldoses(醛醣) or ketoses(酮醣), depending on whether the molecule contains an aldehyde function
or a ketone group
3. Hexoses are the most abundant sugars in nature
4. aldose 的命名常以-ose 結尾；ketose 則以-ulose 結；xylose(為醛醣)，xylulose(為酮醣)
5. 字根字首表：
4C：Eryth-
5C：Ribo-、Arabino-、Xylo-
6C：Gluco-、Manno-、Galacto-

 Stereochemistry Is a Prominent Feature of Monosaccharides

1. aldoses 碳數大於 3 與 ketoses 碳數大於 4 的醣類接有 chiral center
2. 糖類的到倒數第二個碳的 OH group 如果在左邊，稱該醣為 L form；若在右邊稱為 D form
3. D-forms of monosaccharides predominate in nature, just as L-amino acids do
4. D or L form 只跟組態有關跟旋光度無關
5. Stereoisomers that are mirror images of each other are called enantiomers
 D- L- is the mirror image(enantiomers)
6. Diastereomers：isomers that have opposite configurations at one or more of the chiral centers but
that are not mirror images of each other
7. Epimers：a diastereomers that differ in configuration of only one stereogenic center
→glucose 與 mannose 為 epimers；mannose 與 talose 互為 epimers；glucose 與 talose 不是 epimers
 Monosaccharides Exist in Cyclic and Anomeric Forms
1. Alcohols react readily with aldehydes to form hemiacetals(1、5 環合)
2. glucose could undergo a similar intramolecular reaction to form a cyclic hemiacetal(1、5 環合)
3. six-membered, oxygen-containing ring is designated a pyranose
4. ketones can react with alcohols to form hemiketals(2、5 環合)
5. The five-membered ring formed is referred to as a furanose
6. 約有 90%的醣類以環型分子的型態存在
7. 在 hemi acetal 形成時，1 號 C 變成 asymmetrical carbon，又被稱為 anomeric carbon，OH 在下為
α(trans)，上為 β(cis)，兩者互為 anomer
8. αβ circle form 是看 anomeric C1/2；DL form 是看倒數第二的碳的 OH
9. Mutarotation involves interconversion of α- and β- forms [optical rotation change with time]

 Haworth Projections Are a Convenient Device for Drawing Sugars

1. D-sugars → α-anomer；L-sugars→ β-anomer
 2. C6-OH not effective due to 7-member ring is unstable ; C2,C3 rings are unstable too
3. In general, aldohexose favors pyranose; ketohexose favors furanose

4. puckered conformations(環張力) leading the two favored structures are the chair conformation and
the boat conformation
5. equatorial → coplanar with the ring ; axial → parallel to an axis
6. bulky substituent groups on rings are more stable in equatorial
7. chair conformations are slightly more stable than boat conformations

 Monosaccharides Can Be Converted to Several Derivative Forms

1. Sugar Acids
 reducing sugar：sugar with free anomeric carbons, they will reduce oxidizing agents (peroxide’
Cu2+, Ag+, ferricyanide)
 Fehling’ solution：用來檢測糖尿病

 convert sugar to sugar acid

 glucose is a reducing sugar, so these reactions are the basis for diagnostic tests for blood sugar
 oxidation of D-glucose to sugar acid
 A. At C1 site form aldonic acid (-onic acid)
B. At C6 site form uronic acid (-uronic acid)
C. At both C1 and C6 form aldaric acid (-aric acid)

2. Sugar Alcohols
 mild reduction (NaBH4 s) of the carbonyl groups of aldoses and ketoses
 alditols, are designated by the addition of -itol to the name of the parent sugar
 alditols are linear molecules that cannot cyclize in the manner of aldoses
 characteristically sweet tasting, and sorbitol, mannitol, and xylitol are widely
 白內障(cataract)會產生 Sorbitol in the eye
 Glycerol and myo-inositol, a cyclic alcohol, are components of lipids

3. Deoxy Sugars：2-Deoxy-d-ribose is a constituent of DNA

4. Sugar Esters：phosphate esters like ATP are important in metabolism
5. Amino Sugars(-amine)：
 including D-glucosamine and D-galactosamine and chitin, contain an amino group instead of a
hydroxyl group at the C2 position
  Muramic acid which is components of the polysaccharides of cell membranes of higher organisms
and also bacterial cell walls
 muramic acid is a glycosamine linked to a 3-carbon acid at C3
 The N-acetyl and N-glycolyl derivatives of neuraminic acid are collectively known as sialic acids

6. Acetals, Ketals, and Glycosides

 basis for oligo- and poly-saccharides
 acetals and ketals can be formed from hemiacetals and hemiketals, respectively (similar to the
reactions of amino acids to form peptides)
 glycosidic bond between the anameric C and the O of the alcohol

7. A deep look：honey
 with fructose at about 38% and glucose at 31% by weight
 predominant form of fructose (67%) is β-D-fructopyranose , the β- and α-fructofuranose forms
accounting for 27% and 6% of the fructose

7-3 What Are the Structure and Chemistry of Oligosaccharides?

 Disaccharides are the simplest oligosaccharides
1. Be able to identify anomeric carbons and reducing and nonreducing ends
2. The end of the molecule containing the free anomeric carbon is called the reducing end, and the
other end is called the nonreducing end → Sucrose is nonreducing sugar
3. Be able to recognize α 1,4 and β 1,4
4. Homodisaccharides：each contain only one kind of monosaccharide
5. 要記得 unit、linkage、homo 與 hetero
  Lactose(galactose-β-1,4-glucose)：Galβ1-4Glc
A. Lactose deficiency leading to lactose intolerance
B. Lactose cannot be absorbed directly
C. Lactase intestine enzyme existed in young, nursing animals
D. Less amount in mature animals
 Sucrose(glucose-α-1, β-2-fructose)：Glcα1-2Fru
A. Table sugar
 Maltose(glucose-α-1,4-glucose)：Glcα1-4Glc
 Cellobiose(glucose-β-1,4-glucose)：Glcβ1-4Glc
A. cellobiose is obtained from the acid hydrolysis of cellulose
B. Maltose exists in the α-configuration, whereas cellobiose is a β-configuration
 Isomaltose(glucose-α1,6-glucose)：
A. obtained in the hydrolysis of some polysaccharides (dextran)
 Trehalose—A Natural Protectant for Bugs
1. Trehalose 是昆蟲的血糖，屬於 nonreducing disaccharide
2. Trehalose may acts as a natural cryoprotectant, protecting the insect from damage due to freezing
temperatures
 A variety of higher oligosaccharides occur in nature
1. Oligosaccharides also occur widely as components antibiotics derived from various sources
2. Erythromycin and Streptomycin is an antibiotic
7-4 What Are the Structure and Chemistry of Polysaccharides?
 Nomenclature for polysaccharides is based on their composition and structure
1. a polysaccharide contains only one kind of monosaccharide molecule, it is a homopolysaccharide,
whereas containing more than one kind of monosaccharide are heteropolysaccharides
2. proteins and nucleic acids → occur only as linear polymers ; polysaccharides → linear/branched
 Polysaccharides serve energy storage, structure, and protection function
1. starch and glycogen are storage molecules
2. chitin, cellulose and mucopolysaccharides (hyaluronic acids 玻尿酸) are structural molecules
3. cell surface polysaccharides are recognition molecules
 Polysaccharides provide store of energy：starch、glycogen、dextrans
1. starch：the most common storage polysaccharide in plants
 which exists in two forms: α-amylose and amylopectin
 Most forms of starch in nature are 10% to 30% a-amylose and 70% to 90% amylopectin

 α-Amylose is composed of linear chains of D-glucose in α(1,4) linkages

A. poorly soluble in water, a-amylose forms micelles in which the polysaccharide chain adopts
a helical conformation
B. Iodine reacts with α-amylose to give a characteristic blue color
 Amylopectin is a highly branched chain of glucose units (every 12 to 30 residues)
A. linear linkages in amylopectin are α(1, 4), whereas the branch linkages are α(1,6)
B. iodine reacts with it to produce a red-violet color

 The starch phosphorylase reaction cleaves glucose residues from amylose, producing glucose-1-
phosphate and limit dextrin
A. endoamylase that splits α(1,4) glycosidic linkages only within the chain
B. the more branches , the more sites for phosphorylase attack
C. branches provide a mechanism for quickly releasing glucose units for metabolism
D. heated starch is easy digested
 2. Glycogen：The major form of storage polysaccharide in animals
 glycogen is found mainly in liver and muscle、is stored energy for the organism
 glycogen is highly branched molecules, with α(1,6) branches every 8 to 12 glucose units
 Like amylopectin, glycogen yields a red-violet color with iodine
 unlike starch, there is no free reducing end but attach covalently to protein (glycogenin)
 Glycogen can be hydrolyzed by both α- and β-amylases
A. Only for α-1,4 glycosidic linkage, as products can be hydrolyzed by glycogen phosphorylase
Via α-amylases produces glucose → endo-amylase
Via β-amylases produce maltose → exo-amylase
B. Only for β-1,6 glycosidic linkage broken by α-1,6 glycosidase
3. Dextran
 main linkage between glucose is a α(1,6) branched polymer of D-glucose units
 repeating unit is isomaltose
 branches can be (1,2), (1,3) or (1,4)
 dextrans formed by bacteria are composition of dental plaque(牙菌斑)
 cross-linked dextrans are used as column chromatography
 Polysaccharides provide physical structure and strength to organism
1. Cellulose：most abundant natural polymer in the world
 most animal cannot digest expect Ruminants
 in cellulose the glucose units are linked by β(1,4)-glycosidic bonds, whereas in α-amylose, the
linkage is α(1,4)

 strands of cellulose form extended ribbons → hydrogen bond in intrachain、interchain、sheets

 a complex polysaccharide in red wine：RGII → low molecule but most complex (essential trace
element boron (硼) attachment)
2. Chitin：
 cell walls of fungi, exoskeletons of crustaceans(節肢動物)
 The structure of chitin is identical to that of cellulose, except that the -OH group on C2 is replaced
by N-acetyl in β(1,4) linkage
 Natural cellulose seems to occur only in parallel arrangements however chitins are parallel or
antiparallel (𝛼、𝛽、𝛾)atrsnds
 the chains of chitin form extended ribbons, taking advantage of multiple hydrogen bonds
 chitin is second most abundant carbohydrate polymer
3. Agarose
 An important polysaccharide mixture isolated from marine red algae
 a chain of alternating d-galactose and 3,6-anhydro-L-galactose, with side chains of 6-methyL-D-
galactose→有分支
 containing large amounts (up to 99.5%) of water
 agar = polymers of agarose and agaropectin

4. Glycosaminoglycans(GAGs)：為 heterosaccharide，由不同的單元體所聚合，常出現在細胞間質中
其上帶的 OH 可以接上 sulfate，因此帶有很多負電，附著在蛋白質上形成 proteoglycan
由 N-acetylglucosamine 與 uronic acid(6 號碳上 OH 氧化成醇)聚合形成的分
不帶有 SO3-的是 hyaluronate(玻尿酸)
 Hyaluronates are important components of the vitreous humor in the eye and of synovial fluid,
the lubricant fluid of joints in the body
 chondroitins and keratan sulfate are found in tendons, cartilage, and other connective tissue
 dermatan sulfate is a component of the extracellular matrix of skin
 GAGs are fundamental constituents of proteoglycans
 heparin anticoagulant substance
 Peptidoglycan is the polysaccharide of bacterial cell walls
1. all bacterial cell walls have a strong, protective peptide–polysaccharide layer called peptidoglycan
2. Gram-positive bacteria have a thick cell wall consisting of multiple layers of peptidoglycan
Gram-negative bacteria have a much thinner cell wall consisting of a single layer of peptidoglycan
between the inner and outer lipid bilayer membranes
3. Peptidoglycan is called murein
4. The tetrapeptides linking adjacent backbone chains contain an unusual 𝛾-carboxyl linkage
5. Gram-positive cell walls, a pentaglycine chain bridges connect tetrapeptides
Gram-negative cell walls direct amide bond between tetrapeptides

 The structure of cell wall

1. Gram-negative bacteria
 The peptidoglycan layer encloses the periplasmic space and is attached to the outer membrane
via a group of hydrophobic proteins
  outer membrane of Gram-negative bacteria is coated with a highly complex lipopolysaccharide,
which consists of a lipid group joined to a polysaccharide made up of long chains with repeating
structures
2. Gram-postitive bacteria
 Having no outer membrane, Gram-positive cells compensate with a thicker wall
 Covalently attached to the peptidoglycan layer are teichoic acids(磷壁酸)
 Animals display a variety of cell surface polysaccharides
1. Animal cell surface contain an diversity of glycoproteins andproteoglycans
2. These polysaccharide structure regulate cell-cell recognition and interaction
3. The uniqueness of the information in these structure is determined by the enzymes that synthesize
these polysaccharide
7-5 What Are Glycoproteins, and How Do They Function in Cells?
 Carbohydrates on proteins can be O-linked or N-linked
1. Many proteins found in nature are glycoproteins because they contain covalently linked
oligosaccharide and polysaccharide groups
2. 為一 post translational modification，在 ER 與高基氏體進行，可提供蛋白質較好的水溶性與穩定性

3. N-linked saccharides are attached via the amide nitrogen of asparagine residues
 N-linked glycoproteins are of three types: high mannose, complex, and hybrid(high mannose and
complex saccharides)
 alter chemical and physical properties of protein
 stabilize protein conformations and/or protect against proteolysis → protein folding
 cleavage of monosaccharide units from N-linked glycoproteins in blood targets them for
degradation in the liver
4. O-linked saccharides are attached to hydroxyl groups (OH) of serine, threonine or hydroxylysine
 function in many cases is to adopt an extended conformation to lift the functional domains of
these proteins above the membrane surface→ glycocalyx(醣被)
  glycocalyx 特別指細菌的細胞表面包著的多醣質與蛋白質
許多疾病可以被 sugar-based therapies 成功治癒。有許多 carbohydrate-based drugs 與 enzyme
或是 glycoconjugates

 Polar fish depend on antifreeze glycoproteins

1. Each of the threonine residues is glycosylated with the disaccharide β-galactosyl-(1,3)-a-N-
acetylgalactosamine
2. This glycoprotein adopts a flexible rod conformation with regions of three fold left-handed helix
3. antifreeze glycoproteins may inhibit formation of ice and further growth of the crystals in the fish
7-6 How Do Proteoglycans Modulate Processes in Cells and Organisms?
 Structure of proteoglycans

1. Proteoglycans are glycoproteins whose carbohydrate moieties are predominantly GAG

(glycosaminoglycans) O-linked to serine residues
2. Components of the cell membrane and glycocalyx
3. The proteoglycan subunits consist of a core protein containing numerous O-linked and N-linked
glycosaminoglycans
 4. Proteoglycans include both soluble proteins and integral membrane proteins
 Versican is a soluble proteins
 serglycin and decorin are soluble proteins, whereas syndecan is a transmembrane protein(inside
domain interacts with cytoskeleton; outside domain interacts with fibronectin)
 rat cartilage proteoglycan 可以避震(cushion)，因為受到壓力時，水分會從軟骨內擠出軟骨組織，
當壓力減去時，水份可以再吸收
 Functions of proteoglycans involve binding to other proteins
1. Many of the functions of proteoglycans involve the binding of specific proteins to the
glycosaminoglycan groups of the proteoglycan
2. Modulation of cell growth processes
 binding of growth factor proteins by proteoglycans in the glycocalyx
 provides a reservoir of growth factors at the cell surface
 heparin inhibits cell proliferation involving internalization of the glycosaminoglycan moiety and
its migration to the cell nucleus.
3. Cushioning in joints：
 absorb large amounts of water
 Hyaluronic acid(玻尿酸) forms backbone of proteoglycan structure
7-7 Do Carbohydrates Provide a Structural Code?
 Lectins translate the sugar code
1. 凝集素在自然中到處存在，它們可以結合游離溶液中的醣類，或者特定蛋白質結構的某一部分上。
它們凝集細胞並（或者）參與糖結合（glycoconjugate）作用
2. Lectins are proteins that bind carbohydrates with high specificity and high affinity
3. Lectins are the translators of the sugar code (細胞之間的辨識，可辨識 carbohydrate 的一類蛋白質)
4. Cell migration、cell-cell interaction、immune response、blood clotting, depend on information
transfer using this code
 Selectins, rolling leukocytes, and the inflammatory response
1. Selectin proteins modulate the inflammatory reactions
2. Selectin-carbohydrate interactions modulate the rolling of leukocytes along the vascular wall, so that
leukocytes can migrate efficiently to the sites of inflammation
3. Selectins of three types are known: E-selectins, L-selectins, and P-selectins
 Galectins mediators of inflammation, immunity and cancer

 C-reactive protein a lectin that limits inflammation damage

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