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Chapter 12 Sugar, Carbohydrates,
and Glycobiology(糖生物学)
1. Carbohydrates are aldehyde or ketone
compounds with multiple hydroxyl groups or
substances that can yield such compounds on
hydrolysis (p. 293)
1.1 Carbohydrates are the most abundant
biomolecules on earth and have multiple roles
in all forms of life.
1.1.1 Carbohydrates serve as energy stores
(e.g., starch in plants, glycogen in animals),
fuels (e.g., glucose), and metabolic
intermediates (e.g., ATP, many coenzymes).
1.1.2 Carbohydrates serve as structural
elements in cell walls of plants (cellulose) or
bacteria (peptidoglycans), exoskeletons of
arthropods (chitin), and extracellular matrixes
of vertebrate animals (proteoglycans).
1.1.3 Carbohydrates serve as recogntion
signals in glycoproteins and glycolipids
determining cell-cell recognition, intracellular
location, and metabolic fates of proteins (thus
sugars, like nucleic acids and proteins, are also
information rich! But codes unknown).
1.1.4 Carbohydrates (ribose and
deoxyribose) form part of the structural
framework of RNA and DNA.
1.2 Carbohydrates can be categorized into
monosaccharides, oligosaccharides, and
polysacchrides.
1.2.1 Monosacchrides are simple sugars
consisting of a single polyhydroxyl aldehyde or
ketone unit (e.g., glyceraldehyde,
dihydroxyacetone, ribose, glucose, galatose,
ribulose, and fructose).
1.2.2 Oligosaccharides contain two
(disaccharides) or a few monosaccharides joined by
glycosidic bonds (e.g., lactose, sucrose, maltose,
some covalently linked sugars in glycoproteins and
glycolipids).
1.2.3 Polysaccharides contain long chains of
(hundreds to thousands) monosaccharide units
joined by glycosidic bonds (e.g., glycogen, starch,
cellulose, chitin, and glycosaminoglycans).
2. Monosacchrides contain one carbonyl group
and two or more hydroxyl groups. (p. 294)
2.1 Monosacchrides can be divided into two
families: aldoses and ketoses.
2.1.1 Aldoses have their carbonyl groups at
the ends of the carbon chains, thus being an
aldehyde.
2.1.2 Ketoses have their carbonyl groups at
places other than the ends,, thus being ketones.
2.1.3 The simplest aldose is glyceraldehyde,
and the simplest ketose is dihyoxyacetone, both
being triose.
2.1.4 Monosacchrides containing four, five,
and six carbon atoms in their backbones are
called tetroses, pentoses (e.g., ribose and
deoxyribose), and hexoses (e.g., glucose and
fructose), respectively. Each has both aldoses
and ketoses.
2.1.5 Hexoses are the most common
monosacchrides in nature, including D-glucose,
D-mannose, D-galactose, D-fructose.
2.2 All the monosacchrides except
dihydroxyacetone contain one or more asymmetric
(chiral) carbon atoms.
2.2.1 The configuration of an asymmetric
carbon in an open chain monosacchride is usually
indicated by the Fischer projection formulas (fig.)
2.2.2 The carbon atoms of a sugar are
numbered starting at the end nearest to the
carbonyl group.
2.2.3 Glyceraldehyde is conventionally used
as the standard for defining D and L
configurations: D-glyceraldehyde has the -OH
group on the right, L-glyceraldehyde has the -OH
group on the left. (fig.)
2.2.4 For sugars with more than one
asymmetric carbon atom, the D- and L- symbols
refer to the absolute configuration of the
asymmetric carbon farthest to the carbonyl group
(e.g., in D-glucose, the -OH on C-5 has the same
configuration as the asymmetric carbon in Dglyceraldehyde, therefore, D- and L- glucoses are
not enantiomers but stereoisomers!)
2.2.5 (p. 295) Most of the monosaccharides
found in living organisms are the D-isomers (e.g.,
D-ribose, D-glucose, D-galactose, D-mannose, Dfructose)
2.2.6 Each stereoisomer has a different
conventional name, ending with “-ose” suffix.
2.2.7 Ketoses are often named by inserting
an “ul” into the name of the corresponding
aldoses (e.g., aldopentose is named as ribose, the
ketopentose is named as ribulose.
2.2.8 Two sugars differing in configuration
at a single asymmetric carbon is called epimers
to each other (e.g., D-glucose and D-mannose are
epimers at C-2; D-glucose and D-galactose are
epimers at C-4).
2.2.9 Monosaccharides easily form
intramolecular hemiacetals (in aldoses) or
hemiketals (in ketoses) in aqueous solutions. (fig.)
2.2.10 The optical activity of D-glucose
slowly changes when dissolved in water.
2.2.12 (p. 297) An aldehyde can react with
one alcohol to form a hemiacetal (two alcohol to
form acetal), a ketone with an alcohol to form a
hemiketal.
2.2.13 In the open chain form of glucose, the
aldehyde group at C-1 and the hydroxyl group at
C-5 react to form two six-membered pyran-like
cyclic stereoisomers: the a-D-glucopyranose (the
-OH group attached to C-1 locates on a different
side from the C-6 atom) and the b-Dglucospyranose (-OH o C-1 on the same side of
the plane as C-6), thus being specifically called
anomers to each other. (fig.)
2.2.14 The ring structures are commonly
shown by Haworth Perspective Formulas:
carbon atoms not explicitly shown, ring plane
(actually not planar!) perpendicular to the plane
of the paper, heavy line projecting (protruding)
toward the reader, -OH groups below the ring
are at the right side of a Fischer projection.
2.2.15 The a and b anomers interconvert
through the open chain form in aqueous solution
to give an equilibrium mixture, a process being
called mutarotation.
2.2.16 Similarly, the C-2 keto group can
interact with the C-5 hydroxyl group in Dfructose to form the a and b-D-fructosefuranoses
(five-membered ring, furan-like).
2.2.17 D-ribose and 2-deoxy-D-ribose also
form corresponding a (and b) furanoses. (This is
what’s in DNA and RNA.)
2.4 The six-membered pyranose ring and fivemembered furanose ring are not planar.
2.4.1 The six-membered pyranose rings
usually take the chair form of conformation with
bulky substituents in equatorial positions, which
makes them less hindered (comparing with the
boat conformation).
2.4.2 The five-membered furanose rings
usually take the envelop form of conformations
with four carbons in the same plane and the fifth
out of the plane. (fig.)
2.4.3 In the furan ribose rings, either C-2 or
C-3 is out of the plane and locates on the same
side of C-5.
2.4.4 The furanose rings can interconvert
rapidly between different conformations states
(thus pentoses are chosen as components of RNA
and DNA).
2.5 The free carbonyl carbons (in open chains) in
monosaccharides can reduce Cu2+ (cupric ion)
to Cu+ (cuprous ion), which in turn forms a red
cuprous oxide precipitate. (oxidoreduction
reaction) (p. 301)
2.5.1 Such monosaccharides are called
reducing sugars.
2.5.2 This color reaction is the basis of
Fehling’s reaction, a qualitative test for the
presence of reducing sugars, was also used to
estimate the glucose levels in blood and urine of
diabetes patients.
2.6 A variety of hexose derivatives exist in living
organisms. (p. 299)
2.6.1 These derivatives include mainly
amino sugars (e.g., glucosamine, galactosamine,
and mannosamine, N-acetyl-glucosamine), deoxy
sugars (e.g., fucose--deoxygenated galactose,
deoxyribose), and acidic sugars (e.g., gluconate-an aldonic acid, glucuronate--an uronic acid).
2.6.2 Amino sugars are often found in
structural polysaccharides (e.g., bacterial cell
walls contain a heterosaccharide made of
alternating N-acetyl-b-D-glucosamine and Nacetylmuramic acid units; arthropod chitin is a
homopolysaccharide made of N-acetyl-b-Dglucosamine).
2.6.3 Glucuronate is attached to bilirubin
(the degraded product of heme) to solubilize it in
bile.
2.6.4 N-acetylneuraminic acid (sialic acid), an
acidic sugar, is a component of many glycoproteins
and glycolipids in higher animals, playing roles in
molecular and cellular recognition.
2.6.5 Sugar phosphates are common
metabolic intermediates in sugar metabolism.
2.7 Abbreviations of common monosaccharides
and their derivatives are often used in describing
oligo- and polysaccharides.
2.7.1 Glucose, galactose, fructose are
abbreviated as Glc, Gal, Fru, respectively. (others?)
3. Monosaccharide units can link with each
other through O-glycosidic bonds to form oligoand polysaccharides.
3.1 Carbohydrates are joined to alcohols and
amines by glycosidic bonds.
3.1.1 An anomeric carbon atom, being a
hemiacetal, can react with an alcohol to form an
acetal.
3.1.2 The C-O bond thus formed is called
an O-glycosidic bond.
3.1.3 An anomeric carbon atom can also be
linked to the nitrogen atom of an amine by an
N-glycosidic bond.
3.2 Disaccharides consist of two
monosaccharides linked through an O-glycosidic
bond.
3.2.1 Sucrose, lactose and maltose are the
most abundant disaccharides in nature.
3.2.2 In sucrose (common table sugar), the
anomeric carbon of one a-D-glucose is joined to
the hydroxyl oxygen atom on C-2 of an b-Dfructose.
3.2.3 In lactose (found mainly in milk) the
anomeric carbon of one b-D-galactose is joined to
the hydroxyl oxygen atom on C-4 of an D-glucose.
3.2.4 In maltose (being the hydrolysis
product of starch), the anomeric carbon of one aD-glucose is joined to the hydroxyl oxygen atom
on C-4 of another glucose.
3.2.5 Sucrose, lactose, and maltose can be
abbreviated as Glc(a1-2b)Fru, (or Fru(b21a)Glc), Gal(b1-4)Glc, and Glc(a1-4)Glc,
respectively.
3.2.6 Both lactose and maltose have a free
anomeric carbon (not involved in glycosidic
bonding) that can be oxidized, thus being
reducing sugars.
3.2.7 The end of an oligo- and
polysaccharide having a free anomeric carbon
is called the reducing end.
3.2.8 Sucrose does not have a reducing end (the
anomeric carbons of both saccharide units are
involved in glycosidic bonding!).
3.2.9 The three disaccharides can be
hydrolyzed into two monosaccharide units by
specific sucrase (also called invertase), lactase (bgalactosidase in bacteria), and maltase existing on
the outer surface of epithelial cells lining the small
intestines. (milk allergy is due to lack of lactase in
the intestines).
3.3 Glycogen and starch are mobilizable stores of
glucose in animals and plants respectively.
3.3.1 Glycogen (mainly in liver and skeleton
muscles) is a polymer of (a1-4) linked glucose units
with (a1-6) linked branches (occurring about once
every 10 glucose residues).
3.3.2 Starch can be linear or branched polymers of
glucose, called amylose and amylopectin,
respectively.
3.3.3 Amylose consists of D-glucose residues in
(a1-4) linkage.
3.3.4 Amylopectin has about one (a1-6)
branch per 30 (a1-4) linkages.
3.3.5 Amylopectin is like glycogen except for
its lower degree of branching.
3.3.6 The (a1-4) linkages of glycogen,
amylose, and amylopectin cause these polymers
(of thousands of glucose units) to assume a
tightly coiled helical structure, which produce
dense granules in many animal or plant cells.
3.3.7 Each amylose has one nonreducing one and
one reducing one, but each amylopectin and
glycogen has one reducing end and many
nonreducing ends.
3.3.8 Starch and glycogen ingested in the
diet are hydrolyzed by a-amylase (present in
saliva and intestinal juice) that break the a1,4
glycosidic linkages between glucose units.
(starting from the nonreducing ends).
3.4 Cellulose and chitin are structural
homopolysaccharides with similar composition
and structures.
3.4.1 Cellulose, like amylose, is a linear
homopolysaccharide of 10,000 or 15,000 D-glucose
residues, but with (b1-4) linkages.
3.4.2 Chitin is a linear homopolysaccharide
composed of N-acetyl-D-glucosamine residues also
with (b1-4) linkages.
3.4.3 The only chemical difference between
cellulose and chitin is the replacement of a
hydroxyl group at C-2 with an acetylated amino
group.
3.4.4 The (b1-4) linkage allow the
polysaccharide chains of cellulose and chitin to take
an extended conformation forming parallel fibers
through intrachain and interchain hydrogen
bonding.
3.4.5 Most animals lack enzymes to
hydrolyze cellulose but some (like termites and
ruminant animals) can use cellulose because of
the cellulase secreted by symbiotic
microorganisms.
4. Highly negatively charged glycosaminoglycans
existing as proteoglycans are found in the
extracellular matrixes of vertebrates.
4.1 Glycosaminoglycan chains are made of
repeating disaccharide units.
4.1.1 One of the monosaccharide unit is
always a derivative of either glucosamine or
galactosamine.
4.1.2 The other monosaccharide is often a
uronic acid.
4.1.3 The sulfate group is often found
forming esters with certain -OH groups, thus
making glycosaminoglycans highly negatively
charged. (function?).
4.1.4 In hyaluronate (a sulfate free
glycosaminoglycan), the disaccharide unit
(containing a D-glucuronic acid and Nacetylglucosamine in (b1-3) linkage) links each
other in (b1-4) linkages.
4.1.5 Chondroitin sulfate, Keratan sulfate,
heparin are also common glycosaminoglycans in
extracellular matrix, usually covalently bound
to proteins.
4.1.6 Hyaluronate does not contain sulfate
and exists as a free polysaccharide.
4.2 Glycosaminoglycans interacts with proteins
(noncovalently and covalently) to form complex
proteoglycans.
4.2.1 Proteoglycans consist of one or more
core proteins and one or more glycosaminoglycans.
4.2.2 The best-characterized proteoglycan is
the one found in cartilage consisting of a single
long molecule of hyaluronate associating
noncovalently with many molecules of core
proteins, each containing covalently bound other
glycosaminoglycans (including chondroitin
sulfate and keratan sulfate).
4.2.3 Proteoglycans provide viscosity, lubrication,
and resilience to the extracellular matrix.
4.2.4 Proteoglycans also have important
roles in mediating cell adhesion (through
integrins and fibronectins), docking proteins
(that stimulating cell growth and proliferation),
morphogenesis and other other unknown ones.
Proteoglycan structure, showing the
trisaccharide bridge, Xylose anomeric
carbon to the hydroxyl of serine
Proteoglycan structure of an integral membrane
protein. Shown is syndecan. Trisaccharide linkers
in blue.
A proteoglycan aggregate of the extracellular matrix. 100
core protein aggrecan. Link proteins mediate interaction
between hyaluronate backbone and core protein.
5. Oligosaccharides are attached to integral
membrane proteins and many secreted proteins to
form glycoproteins.
5.1 The number of possible arrangements and
combinations of monosaccharide types and
glycosidic linkages in an oligosaccharide can be
astronomical.
5.1.1 Sugar residues commonly found in
glycoproteins include Fuc, Gal, Man, GalNAc,
and Sia (or NeuNAc).
5.1.2 Glycosidic linkages can be (1-2), (1-3),
(1-4), (1-6), (2-3), (2-6), …etc.
5.1.3 Many more oligosaccharides can be
formed from four monosaccharides than
oligopeptides from four amino acids.
5.1.4 Oligosaccharides can be extremely
information rich!
5.2 The oligosaccharide can be covalently linked
to Ser and Thr residues on proteins by Oglycosidic bonds, or to Asn residue by Nglycosidic bonds.
5.2.1 glycophorin, a well-studied membrane
glycoprotein, contains 15 O-linked
oligosaccharides and one N-linked one.
5.2.2 N-linked oligosaccharides usually
contain a common pentasaccharide core
consisting of three Man and two GlcNAc
residues.
5.3 Carbohydrate-binding proteins mediate many
biological recognition processes.
5.3.1 The terminal sugar residues on a
glycoprotein can serve as a signal that directs liver
cells to remove the protein from the blood (e.g.,
exposed Gal residues of a trimmed glycoproteins
are detected by the asialoglycoprotein receptors in
the plasma membranes of liver cells).
5.3.2 Plants contain many specific
carbohydrate-binding proteins called lectins,
which contain two or more sites that bind specific
carbohydrate units.
5.3.3 Some viruses gain entry into host cells
by adhering to cell-surface carbohydrates (e.g.,
influenza virus contains a hemagglutinin protein
that recognizes sialic acid residues on cells lining
the respiratory tract).
5.3.4 Carbohydrate are critical in the
interaction bewteen sperm and ovulated egg (a
carbohydrate on the surface of the egg is
recognized by a receptor on the sperm).
5.3.5 Carbohydrate play important roles in
cell adhesions.
5.3.6 The carbohydrate codes are waiting to
be deciphered!
Interactions bwt cells and extracellular matrix.
Mediated by integrin and fibronectin. Note the close
association of collagen with fibronectin.
Oligosaccharide linkages in glycoproteins. Common
examples
Determinant of
serotype of
bacterium
Common among
bacteria
Helicobacter pylori cells colonize on the surface of the gastric
epithelium, causing ulcers. Lectin binds Leb oligosaccharides.
Lectins are in light purple. They mediate cell-cell
interactions.