BIOCHEMISTRY FIRST SEMESTER

LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022

CARBOHYDRATES AND GLYCOBIOLOGY
OUTLINE
I. Sugars: Structures and Stereochemistry
II. Reactions of Monosaccharides
III. Important Oligosaccharides
IV. Structures and Functions of Polysaccharides
V. Glycoconjugates: Proteoglycans, Glycoproteins,
and Glycolipids
CARBOHYDRATES
• In scientific literature, sugar is also known as
carbohydrate (or hydrate of carbon)
• Most abundant biomolecules on Earth • Monosaccharides: monomers (building blocks) of all
o Each photosynthesis converts more than 100 carbohydrates.
billion times of carbon dioxide and water into • Called differently depending on the number of
carbohydrates. Certain carbohydrates are a carbons and main functional group.
dietary staple of most parts of the world. Rice is • Simplest monosaccharides contain three carbons
covered with starch, which is a form of (triose).
carbohydrates. The oxidation of carbohydrates is o Even if they have a ketone or aldehyde in their
a central energy yielding pathway in most non- functional group, as long as, they have three
photosynthetic cells. We consume carbons, we call them as triose.
carbohydrates to yield energy. And if we don’t use o Glyceraldehyde (aldotriose)
it, at the moment, we store them in another form. ▪ Simplest aldotriose
o Insoluble carbohydrate polymers serve as ▪ Aldehyde as functional group, followed by a
structural and protective elements in the cell wall hydrogen, then hydroxyl group on the second
of bacteria and plants and in the connective tissue carbon and another hydroxyl group on the
of animals. Other carbohydrates lubricate skeletal third carbon. There is multiple hydroxides,
joints and participate in recognition and adhesion hydroxyl groups. Hence, it is poly OL.
between cells. Most complex carbohydrate o Dihydroxyacetone (ketotriose)
polymers are covalently attach the proteins or ▪ The simplest ketotriose
lipids and act as signals. ▪ Hyroxyacetone has its functional group on
• Has three major size classes: monosaccharides, the second carbon. The same structure will
oligosaccharides, and polysaccharides come up even if you reverse or rotate it on
• Polyhydroxyaldehydes (aldose) or different direction.
polyhydroxyketones (ketose)
• Name ends in -ose
• Many, but not all, have the empirical formula: (CH2O)n
o n = number of molecules
o The empirical formula for carbohydrates contains
of C and a molecule. The water is known as
hydrate, hydrating the carbon.
o Some contain nitrogen, phosphorous, or sulfur
• Play a number of important roles in biochemical
processes • Monosaccharides also exhibit stereoisomerism
o Major sources of energy o Stereoisomerism is the difference in the
▪ Go foods to spend energy in doing activities configuration of a chemical structure in space.
o Have a key role in cell surfaces such as cell-cell Even if their connectivity is the same but their
interactions and immune recognition orientation in space is different—they would be
o Essential structural components different compounds.
WHAT IS UNIQUE ABOUT THE STRUCTURE OF o Simplest carbohydrate that exhibits
SUGARS? stereoisomerism is glyceraldehyde.
Dihydroxyacetone has its functional group in the

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BIOCHEMISTRY FIRST SEMESTER
LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022
CARBOHYDRATES AND GLYCOBIOLOGY
middle of its structure. So, rotating or reversing it
would yield the same structure.
• Mirror-image stereoisomers are called enantiomers.
• Non mirror-image stereoisomers are called
diastereomers
• Configuration: three-dimensional arrangement of
groups around the chiral carbon.
o Chiral carbon contains four different groups
attached to it. Stereoisomers differ from each
If you are determining if it is L or D, you would always
other in configuration.
look at its second to the last carbon.

• Stereoisomers differ from each other in configuration.

o D,L system is widely used This is a wedge bond, meaning directed towards the
o R,S system is also used, a more recent system back (vertical). The same thing for the solid bond,
▪ No one-to-one correspondence between the projecting towards you (horizontal).
two systems (e.g., some D-isomers are R,
while others are S)
• Possibilities for stereoisomerism increase as the
number of carbon atoms increases.
o The number of stereoisomers for four carbon
monosaccharides increases.
• To show structures of the molecules, Fischer
projection is used.
o Fischer was developed by Emil Fischer during
1970s or 1980s.
o Shows the two-dimensional perspective of the
molecular structure
▪ It is the best projection for liner
carbohydrates. We would be able to
distinguish if it is a galactose or whatever that
monosaccharide is. We would be able to
know if it is a levo-rotatory or dextro-rotatory
molecule.
• In a Fischer projection, the orientation of the bonds Numbering of carbon atoms in sugars. (a) Examples of
represent the direction of the bond an aldose (D-glucose) and a ketose (D-fructose), showing
o Vertical bonds: directed behind the plane the numbering of carbon atoms. (b) A comparison of the
▪ Towards the back; away from the viewer structures of D-glucose and L-glucose.
o Horizontal bonds: directed in front of the plane • This is how we number carbon atoms in sugars.
▪ Towards the viewer Showing on the picture above is an aldose and
ketose.
• At A. The one involved in the aldehyde group is
written at the top—the most oxidized because of its
double bond, designated as the carbon one. In the

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BIOCHEMISTRY FIRST SEMESTER
LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022
CARBOHYDRATES AND GLYCOBIOLOGY
ketose shown, the ketone group becomes C2—the same configuration. However, they have different
carbon atom, next to the top. Note: the carbon configurations and arrangements. Both D-Erythrose
containing the priority functional group is closest to and D-Threose have OHs on the plane’s right side.
the number one carbon. The designation of the However, for the Erythrose second carbon, the OH is
configuration if it is L or D, depending on the chiral found on the right but for D3, it is on the left. If you try
carbon’s arrangement with the highest number. In the to superimpose the D-Threose and D-Erythrose with
case of both glucose and fructose, this is carbon 5, each other, they are not mirror images of each
containing six carbons. To decide whether it is an L or other—non stereoisomers are called
D configuration, it will depend on the carbon with the diastereomers. So, D-Erythrose and L-Erythrose are
highest number (highly oxidized). It should always be enantiomers whereas, the D-erythrose and L-
the penultimate carbon or carbon which is second Threose are diastereomers. Diastereomers that
to the last of the numbering system. differ from each other in the configuration having only
• At B, they are the mirror of each other. So they are one chiral carbon are called epimers. If it is multiple
enantiomers. carbons are no longer called an epimer so it is
generally diastereomer.
• Most of the carbohydrates that exist in the body are
aldohexoses, so we do not talk about ketotetroses.
They are not that abundant except for sugar, such as
sucrose where it’s a dimer of glucose and a fructose
(ketohexose). Aldopentoses have three chiral
carbons. Aldotetroses have three chiral carbons.
Aldopentoses have three chiral carbons.
Aldohexoses have four chiral carbons. Aldopentoses
have two to the third power—possibility for 8
isomers (4D and 4L).
• Most of the sugars, we encounter in nature, especially
in food containing either five or six carbon atoms.
Glucose is the go-to carbohydrate when it comes to
energy-yielding. Glucose is an ubiquitous energy
source and ribose plays an important role in the
structure of nucleic acids.

This is what happens as another carbon is added to

glyceraldehyde to give carbon for carbon sugar.
• Observe A (upper portion). You add carbon sugar on
the middle. Aldetetrose have two chiral atoms, C2 and
C3. Note that: For sugars, all of the carbon in the
middle has a hydroxyl group—polyhydroxy
structure. So there two-squared or four possible
stereoisomers because you can create a mirror image
for the two. Two of the isomers have the D-
Aldoses containing from three to six carbon atoms, with
configuration. The two D isomers have the same
the numbering of the carbon atom shown. Note that the
configuration at C3 and the two L isomers have the

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BIOCHEMISTRY FIRST SEMESTER
LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022
CARBOHYDRATES AND GLYCOBIOLOGY
figure shows only half the possible isomers. For each If OH is projected upward, it is beta.
isomer shown, there is an enantiomer that is not shown,
the L-series.
• Aldopentoses have three chiral carbons.
WHAT HAPPENS IF A SUGAR FORMS A CYCLIC
MOLECULE?
• Sugars (especially 5-6 C) normally exist as cyclic
molecules.
o Aldopentoses and aldohexoses
o Most carbohydrates are found cyclic rather then
linear
• Cyclization is a result of interaction between
functional groups
o C1 (aldehyde) and C5 (alcohol) forms cyclic
hemiacetal (aldohexoses)
o C2 (ketone) and C5 (alcohol) forms cyclic
hemiketal (ketohexoses)
• Carbonyl carbon becomes a new chiral center:
anomeric carbon
You can see the difference between alpha and beta on
• Cyclic sugar can take two different forms (α and β) its carbon one. In alpha, the hydroxyl is located on the
and are called anomers of each other. right. AS for beta, it is located on the left. You would
have a difficulty in determining the L and D, since the 5 th
carbon is absent with hydroxy group. NOTE: We
establish the L and D if the linear form before the
cyclization process is determined first.
NOTE: HAWORTH PROJECTION FORMULAS. When
Free carbon will be attracted more on the alcohol. It is an
you look at the different isomers of a particular carbon of
electrophilic attack then you have a free-floating
a particular monosaccharide, it depends entirely from the
hydrogen which will attach to the oxygen, resulting in an
second carbon until its ultimate carbon. Glucose is
hemiacetal.
different from aloes—an epimer.

D-glucose. The 1st carbon will react on the 5th carbon, then
the cyclization process occurs. The proximity of carbon 5
to carbon 1 will allow the cyclization process, forming Fischer projection formulas of three forms of glucose.
hemiacetal. Note that the α and β forms can be converted to each
Double bond will be lost. The H can be projected other through the open-chain form. The configuration at
downwards or upwards depending on its orientation on carbon 5 determines the D designation.
pace before the cyclization occurs. Since it is a • Fischer projection formulas are useful for describing
hemiacetal, relatively unstable, it could reverse to its stereochemistry of sugars in their linear forms
original form and undergo another cyclization process, • Haworth projection formulas are more useful in
yielding another anomer. describing cyclic structure.
If the OH is projected below—it is an alpha. o Structures are viewed from the edge of the plane.

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BIOCHEMISTRY FIRST SEMESTER
LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022
CARBOHYDRATES AND GLYCOBIOLOGY
▪ Imagine you have a Piattos, which
resembles your Glucose, then put it on your
palm. Look at it at a 45-degree angle below
your eye.
o Five-membered rings are called furanose
o Six-membered rings are called pyranose

A comparison of the Fischer, complete Haworth, and

Haworth representations of sugar structures. (a) A abbreviated Haworth representations of α- and β-D-
comparison of the structure of furan with Haworth glucose (glucopyranose) and β-D-ribose
representations of furanoses. (b) A comparison of the (ribofuranose). In the Haworth representation, the α-
structure of pyran with Haworth representations of anomer is represented with the OH group (red)
pyranoses. (c) α-D-Glucopyranose in the Haworth downward, and the β-anomer is represented with the OH
representation (left), in the chair conformation (middle), group(red) upward.
and as a space-filling model (right). We usually use the D-configuration because it is the most
• Glucopyranose exists in the chair confirmation rather abundant form of glucose in the body.
than the Haworth confirmation. This is still cyclic REACTIONS OF MONOSACCHARIDES
though for Hayworth, we use Hayworth just to even WHAT ARE SOME OXIDATION-REDUCTION
out the edges. For chair confirmation in which glucose REACTIONS OF SUGAR?
or mostly six carbon sugars exist in the body. • Redox reaction of sugars plays key roles in
biochemistry
o Oxidation: releases the energy stored in
carbohydrates, takes place in cellular respiration
o Reduction: forms the carbohydrate, takes place
in photosynthesis and in certain species of
bacteria and soils
▪ Forms the glucose and fructose
• Oxidation reaction of sugars are used to identify the
sugar (laboratory practices)
o Aldehydes can be oxidized to give carboxyl group
of acids (-COO-), used to test for aldoses
▪ COH group found in carbon one of your
structure
▪ When aldehyde is oxidized, some oxidizing
agent must be used.

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BIOCHEMISTRY FIRST SEMESTER
LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022
CARBOHYDRATES AND GLYCOBIOLOGY
o Aldoses are called reducing sugars ▪ Deoxy sugars means one of the alcohols or
▪ Because they used up the oxidizing agent one of the hydroxyl groups in the structure
▪ Ketoses can also be reducing sugars does not contain oxygen.
because they isomerize to aldoses ▪ A hydrogen atom is substituted by one of the
o In the cyclic form, the compound formed by the hydroxyl groups of the sugar and one of these
oxidation of aldose is called a lactone. oxy sugars is L-fucose or what we call 6-
• Two types of reagents are used to detect the Deoxy-b-L-galactose, a sugar found in the
presence of reducing sugars: silver ammonia carbohydrate portions of the glycoproteins,
complex ion, Ag(NH3)2+ (Tollen’s test) and glucose including the blood group antigens.
oxidase (which is specific only for glucose but not o Another deoxy sugar, 2-Deoxy-b-D-ribose, is
other reducing sugars). found in DNA

Structures of two deoxy sugars. The structures of the

parent sugars are shown for comparison.
Oxidation of a sugar to a lactone. An example of an • When the carbonyl group of a sugar is reduced to a
oxidation reaction of sugars: oxidation of α-D-glucose hydroxyl group, the resulting polyol is known as an
hemiacetal to give a lactone. Deposition of free silver as alditol. C=O C→OH
a silver mirror indicates that the reaction has taken place. o CO is reduced to a hydroxyl group; hydrogen is
• The H from the OH is removed and becomes a added. Hydrogenation is a form of a
ketone. Silver ions is also yielded. Ag2+ will float reduction—the resulting polyol is called an
around the solution until it encounters the surface of albitol.
the tube inside until it forms a silvery mirror complex.
• If you see a silver mirror in an unknown test—
Tollen’s test because it is an indication of the yielding
of silver ions from your agent to form this lactone.

Two well-known alditols are economically important:

xylitol and sorbitol (e.g., artificial sweeteners)
VITAMIN C IS RELATED TO SUGARS
• Also known as ascorbic acid
• Vitamin C is an important lactone. It is related to
sugars because it is for those organisms that
synthesize Vitamin C. They usually derive Vitamin C
A silver mirror produced by an aldehyde. After the from the carbohydrates that they take in.
addition of Tollens reagent to an aldehyde, a silver • Vitamin C is an unsaturated lactone with a five
mirror has been deposited in the inside of this test tube. membered ring structure.
WHAT ARE SOME OXIDATION-REDUCTION
REACTION OF SUGARS?
• There are also reduced sugars (oxidizing sugars) that
are biochemically important
o A deoxy sugar, L-fucose, is found in the
carbohydrate portions of glycoproteins including
There is a characteristic of double bond, a ketone, and
the ABO blood-group antigens
an esterified oxygen which is a characteristic of a
lactone.
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BIOCHEMISTRY FIRST SEMESTER
LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022
CARBOHYDRATES AND GLYCOBIOLOGY
• Most animals synthesize Vit. C except for guinea pigs
and primates, including humans.
o Our metabolism does not synthesize Vitamin C
so we have to take them orally.
• Ascorbic acid is taken through diet; deficiency leads
to scurvy The formation of a phosphate ester of glucose. ATP is
o It is a disorder characterized by dysfunctional the phosphate group donor. The enzyme specifies the
collagen, involving weakened collagen (affecting interaction with —CH2OH on carbon 6.
the hair, teeth, skin) This is present during glycolysis.
o Scurvy: collagen (protein) has structural defects, WHAT ARE GLYCOSIDES, AND HOW DO THEY
causing skin lesions and fragile blood vessels. FORM?
Hydroxyproline (amino acid derivative) is • It is possible for a sugar hydroxyl group (ROH)
important for the stability of collagen. bonded to the anomeric carbon to react with another
▪ Hydroxyproline is located in the crosslinks of hydroxyl group (R’-OH) to form a glycosidic linkage
the collagen. So, removing it can cause (R’-O-R), or a compound known as a glycoside.
collagen to weaken. o Glycosidic linkage is not an ether
o Ascorbic acid is essential for the activity of prolyl o The hydrolysis of glycosidic linkages results to
hydroxylase (enzyme), which converts proline to the original alcohol, not a new compound.
hydroxyproline. • The bond formed is called a glycosidic bond.
▪ Adding hydroxyl to create hydroxyproline
then being synthesized in the cells
o Lack of ascorbic acid affects this activity, leading
to the fragile collagen responsible for the
symptoms of scurvy
WHAT ARE SOME IMPORTANT ESTERIFICATION
REACTIONS OF SUGAR?
• Hydroxyl groups of sugars can react with acids and An example of the formation of a glycoside. Methyl alcohol
derivatives of acids to form esters. (CH3OH) and an α-D-glucopyranose react to form the
• Phosphate esters are important because they are the corresponding glycoside.
usual intermediates in the breakdown of We usually omit the H in writing Haworth projection, the
carbohydrates to provide energy. same way with line angle formula. If you react which is a
hemiacetal with a methyl alcohol, you have CH 3OH. The
picture below will show the process.

The hydroxyl group or any hydroxyl

group in the structure can react with acids and derivatives
of acids to form esters. You will get H-O-R, connecting the
sugar with its derivative, phosphate esters meaning the
molecule attached here is PO3-. So, PO3- is the
intermediate in the breakdown of carbohydrates to
provide.
o Formed by the transfer of phosphate from ATP to
give phosphorylated sugar and ADP.
• These reactions are important in carbohydrate
metabolism.

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CARBOHYDRATES AND GLYCOBIOLOGY

If you hydrolyze or
reintroduce water, CH3OH will reform, and H will bind with
O. That is the intermediate that needs the lowest energy A disaccharide of β-D-glucose Both anomeric carbons
unless you are going to introduce another oxygen (C-1) are involved in the glycosidic linkage.
molecule, creating a carboxylic acid. The formation of In here, you have the same monomeric units, repeating
glycosidic bond is important because these glycosidic monomeric units (alpha will link to alpha).
bonds between monosaccharides are basis for • Chemical nature of oligosaccharides and
polysaccharides and oligosaccharides’ formation. polysaccharides depend on
• Glycosidic bonds formed through the linkage of the O o 1. the monosaccharides that are linked together
atom of one sugar to another are called O-glycosidic ▪ If it is a glucose, galactose, alose, fructose or
bonds ribose.
o N-glycosidic bonds can be found in nucleic acids, o 2. the particular glycosidic bond formed
especially between the nitrogenous bases and • Example: the difference between cellulose and starch
the five-carbon sugar depend on the glycosidic bond formed between
o S-glycosidic bonds are found in thioglycosides, glucose monomers.
where O is replaced by sulfur o Variation in glycosidic linkages can form linear
▪ It comes in fewer quantity compared to N- and branched chain polymers
and O-glycosidic.
• Glycosides derived from furanose (5 C): furanosides
• Glycosides derived from pyranose (6 C): pyranosides
• Glycosidic bonds between monosaccharides are the
basis for the formation of oligosaccharides and
polysaccharides The linear polyglucose chain occurs in amylose. All
• Glycosidic linkage can take various forms; numerous glycosidic bonds are (1 → 4).
combinations are found in nature. Amylose is a type of starch. All glycosidic bonds that form
• The hydroxyl groups (-OH) are numbered so that they in amylose are alpha one for glycosidic bonds.
can be distinguished; the numbering follows the
carbon atoms.

Two different disaccharides of α-D-glucose. These

The branched-chain polymer occurs in amylopectin and
two chemical compounds have different properties
glycogen. Branched polyglucose-chain glycosidic bonds
because one has an α(1→4) linkage and the other has an
are (1 → 6) at branched points, but all glycosidic bonds
α(1→6) linkage.
along the chain are (1 → 4).
You will know if it is a beta if it goes straight or OH is
Every 10th or 4th monomeric residue, you will find a 1 → 6
projected upwards. These linkages are used to determine
glycosidic bond. This will indicate a branching off and will
the reactivity nature and structure of oligosaccharides and
continue towards how many molecules.
polysaccharides. Properties of them will rely on the
existing glycosidic bond between your monomeric units.

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BIOCHEMISTRY FIRST SEMESTER
LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022
CARBOHYDRATES AND GLYCOBIOLOGY
• In testing the presence of reducing sugars, the
anomeric carbon is usually involved in the
reaction. It is also frequently involved in the
glycosidic linkage.
• Note that the internal anomeric carbon in an
oligosaccharide or a polysaccharide is not free to
give a positive result for reducing sugar.
• Only if the end residue is a free hemiacetal rather than
a glycoside will there be a positive test for reducing
sugar.
o Even though a particular polysaccharide or The structures of N-acetyl-β-D-glucosamine and N-
oligosaccharide contains a reducing sugar such acetylmuramic acid.
as glucose, if it is found in the chain, the anomeric
carbon where the aldehyde is found is not
available. REASON: It participates in the
formation of the glycosidic chain.

Reducing sugars. A disaccharide with a free hemiacetal

end is a reducing sugar because of the presence of a free Some hexose derivatives important in biology. In
anomeric aldehyde carbonyl or potential aldehyde group. amino sugars, an -NH2 group replaces one of the -OH
Even though, glucose participates in the formation of a groups in the parent hexose. Substitution of -H for -OH
glycosidic bond then there would be no positive result for produces a deoxy sugar; note that the deoxy sugars
the presence of a reducing sugar. shown here occur in nature as the L-isomers. The acidic
WHAT ARE SOME OTHER IMPORTANT DERIVATIVES sugars contain a carboxylate group, which confers a
OF SUGARS? negative charge at neutral pH. D-glucono-δ-lactone
• Amino sugars: carbohydrates that contain amino results from formation of an ester linkage between the C-
group or its derivatives that substitutes for the 1 carboxylate group and the C-5 (also known as the
hydroxyl group of the parent sugar carbon) hydroxyl group of D-gluconate.
o In N-acetyl amino sugars, the amino group itself
carries the acetyl group (CH3-CO-) as a
substituent
• Important examples of amino sugars: N-acetyl-β-D-
glucosamine and N-acetyl-β-muramic acid. These
are components of bacterial cell walls.
o If you try to determine bacteria, you should be
able to choose the correct stain for a particular
bacteria.

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BIOCHEMISTRY FIRST SEMESTER
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CARBOHYDRATES AND GLYCOBIOLOGY
SOME IMPORTANT OLIGOSACCHARIDES • Familiarize yourselves with the connections of the 3
• Oligomers (Grk. oligos = few) of sugars are usually main monosaccharides to form the disaccharides.
disaccharides formed by linking two
The structures of several important disaccharides.
monosaccharides units.
Note that the notation —HOH means that the
• Three of the most important examples of
configuration can be either α or β. When a D sugar is
oligosaccharides are disaccharides
drawn in this orientation, if the —OH group is above the
o Sucrose
ring, the configuration is termed β. The configuration is
o Lactose
termed α if the —OH group is below the ring. Also note
o Maltose
that sucrose has no free anomeric carbon atoms.
WHAT MAKES SUCROSE AN IMPORTANT
COMPOUND?
• Sucrose (table sugar) is extracted from sugar cane
and sugar beets.
• Monosaccharide units: α-Dglucose and β-D-fructose.
• C-1 of the glucose is linked to the C-2 of the fructose
in a α,β(1 → 2) glycosidic linkage.
• NOT a reducing sugar, but monomeric substituents
are.

• If you try to test for reducing sugars for sucrose (the

disaccharide in the image above), it will not yield a
positive result because the anomeric groups are not
free for a carboxyl group to yield a positive result.
• Consumption leads to hydrolysis of monomers which
are then used as energy sources.
• SUCROSE leads to the hydrolysis of monomers
which are then used as energy sources. While
GLUCOSE is directly involved in glycolysis whereas
fructose is isomerized to glucose so there needs to be
an energy input before fructose is utilized by the body.
• Humans consume large quantities (which can lead to
health problems); excessive consumption contribute
to health problems which led to a search for other
sweetening agents.
o Fructose: sweeter than sucrose, but changes
texture of food
o Saccharin and cyclamates: causes cancer in lab
animals
o Aspartame: suspected to cause neurological
problems

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BIOCHEMISTRY FIRST SEMESTER
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CARBOHYDRATES AND GLYCOBIOLOGY
ARE THERE ANY OTHER DISACCHARIDES • Yeast contains enzymes that hydrolyze starch to
IMPORTANT TO HUMANS? maltose then glucose, which is fermented during
brewing.
THE CASE OF LACTOSE INTOLERANCE
• Sugar intolerance results from the inability to either
digest or metabolize certain sugars, usually due to
missing or defective enzymes.
• Some adults have a deficiency in the enzyme lactase
in the intestinal villi.
• Adults without the enzyme LACTASE, has Lactose
Intolerance
• LACTASE – an enzyme that hydrolyzes lactose into
• Lactose: made up of β-D-galactose and D-glucose its component galactose and glucose in the
linked at β(1→4) INTESTINAL VILLI in the digestive system.
• A reducing sugar because the anomeric carbon of
glucose is free.
• The ANOMERIC CARBON (the carbon on the
rightmost tip of the glucose in the image above) is
free, as opposed to containing an aldehyde. So it is
free to yield a carboxyl group for a positive result. It’s
free to yield a lactone.
• Have two anomeric forms, each must have the β-D-
galactose while the D-glucose can be either α or β.

• Build-up of lactose causes bacterial lactase to act on

it, releasing H, CO2, and organic acids instead of
galactose and glucose.
• Maltose is obtained from the hydrolysis of starch • The bacterial products lead to digestive problems
• Consist of two residues of D-glucose in an α(1→4) such as bloating and diarrhea; the products further
linkage. draw water via osmosis thus aggravating the
• Differs from cellobiose (from cellulose) only in the diarrhea.
glycosidic linkage which is β(1→4)
• Mammals can digest maltose BUT NOT cellobiose.
o The chemical reactivity of your sugar depends
entirely (especially for polysaccharides) on the
type of monomeric units or the type of glycosidic
linkage.
o Ex. the difference between maltose and
cellobiose is just the alpha and beta, yet they are
entirely different in terms of digestibility in
mammals.

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BIOCHEMISTRY FIRST SEMESTER
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CARBOHYDRATES AND GLYCOBIOLOGY
o Heteropolysaccharide: polymer consisting of
more than one type of monosaccharide.
• Complete characterization of a polysaccharide
includes
o Specification of which monomers are present
o Sequence of monomers
o Specific type of glycosidic linkage
HOW DO CELLULOSE AND STARCH DIFFER FROM
ONE ANOTHER?
• Cellulose is the major structural components of plant
cell walls.
o Linear homopolysaccharide of βD-glucose, with
all residues linked in β(1→4) glycosidic bonds.
o Individual polysaccharide chains are hydrogen-
bonded together.
• Animals are not capable of hydrolyzing cellulose
• Even if lactase is present, other people cannot
because of the absence of cellulase.
metabolize galactose.
o Cellulase attack the β(1→4) glycosidic bonds
• If an enzyme that catalyzes the reaction pathway for
o However, Certain bacteria have cellulase,
galactose is absent, galactose builds up resulting to
including bacteria found in termite gut and
galactosemia.
ruminants.
o Severe problem in infants because galactose is
▪ Ruminants – animals that have a four-
converted to GALACTITOL, which cannot be
chambered gut/stomach. They have bacteria
excreted. The accumulation draws in water and
in their gut that can degrade cellulose into
causes swelling, edema causes damage
glucose. Ex. cows, goats
o The critical tissue here is the brain, when the
o Again, the disaccharide that is yielded from the
galactose builds up in the brain, it is critical.
metabolism of cellulose is cellobiose
• Dietary therapy for lactose intolerance and
galactosemia are different.
o Lactose intolerant people must avoid taking in
lactose throughout their lives.
▪ Permanent
o Galactosemia-afflicted people must avoid milk
during their childhood. The development of
metabolic pathways for galactose during puberty
alleviates the problem in most individuals.
▪ Mostly only during childhood
STRUCTURES AND FUNCTIONS OF
POLYSACCHARIDES
• So we have oligomers, which are few repeating units
of monosaccharides. Now we have long chains of
monosaccharides.
• When many monosaccharides are linked together,
the result is a polysaccharide.
• Polysaccharides that occur in organisms are usually
composed of a very few types of monosaccharide. The polymeric structure of cellulose. β-Cellobiose is
o Homopolysaccharide: polymer consisting of the repeating disaccharide. The monomer of cellulose is
only one type of monosaccharide. the β-anomer of glucose, which gives rise to long chains
▪ Ex. glucose, glucose, glucose, glucose, that can hydrogen-bond to one another.
glucose, … OR galactose, galactose,
galactose, galactose, …

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BIOCHEMISTRY FIRST SEMESTER
LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022
CARBOHYDRATES AND GLYCOBIOLOGY
• Starch are polymers of α-D-glucose. Has different o Debranching enzymes that attack α(1→6) are
forms; can be distinguished from one another by their used by plants and animals.
degrees of chain branching.
o Amylose: linear polymer linked at α(1→4)
glycosidic bonds
o Amylopectin: branched chain polymer with
branches starting at α(1→6) linkages along the
chain of α(1→4)

The structure of starch is based on the α-anomer of

glucose. The monomer of starch is the αanomer of
glucose, which gives rise to a chain that folds into a helical
form. The repeating dimer has α(1→4) linkages
throughout.
Amylose and amylopectin are the two forms of starch. The starch–iodine complex. Amylose occurs as a helix
Note that the linear linkages are α(1→4), but the branches with six residues per turn. In the starch– iodine complex,
in amylopectin are α(1→6). Branches in polysaccharides the iodine molecules are parallel to the long axis of the
can involve any of the hydroxyl groups on the helix. Four turns of the helix are shown here. Six turns of
monosaccharide components. Amylopectin is a highly the helix, containing 36 glycosyl residues, are required to
branched structure, with branches occurring at every 12 produce the characteristic blue color of the complex.
to 30 residues. HOW IS GLYCOGEN RELATED TO STARCH?
• Starch is to plants as glycogen is to animals: both are
storage polymers.
• Glycogen is a branched-chain polymer of α-D-
glucose; similar to the amylopectin part in this regard.
o Glycogen is more highly branched, every 10th
residue is a branch compared to every 25th in
amylopectin
• Starch are storage molecules and therefore should o Average chain length is 13 glucose residue, and
have a mechanism for releasing glucose. 12 layers of branching
o Enzymes can hydrolyze these different forms of o Has glycogenin at its core, an enzyme that acts
starch: α and β-amylase. as a primer to convert glucose into glycogen.
o β-amylase is an exoglycosidase, cleaves from the • Found in animal cells in granules, observed in liver
non-reducing end of the polymer, produces and muscle cells.
maltose.
o α-amylase is an endoglycosidase, cleaves
anywhere along the chain to produce glucose and
maltose.
• Amylose can be completely degraded to glucose and
maltose by the two amylases; amylopectin is not
completely degraded because the branches are not
attacked.
o The branches that contains the α(1→6) glycosidic
bonds cannot be hydrolyzed by the alpha and
beta amylase. So instead of using alpha and beta
amylase, plants and animals actually use
A comparison of the degrees of branching in amylopectin
debranching enzymes.
and glycogen.

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BIOCHEMISTRY FIRST SEMESTER
LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022
CARBOHYDRATES AND GLYCOBIOLOGY
• Plays a structural role, has a fair amount of
mechanical strength because of hydrogen bonds.
o Major component of the exoskeletons of
invertebrates; cell walls of algae, fungi, and yeast.

A core protein of glycogenin is surrounded by branches

of glucose units. The entire globular complex may
contain approximately 30 000 glucose units.
• The number of branch points in the glycogen structure
is significant for two reasons:
o 1. a more branched polysaccharide is more
The polymeric structure of chitin. N-Acetylglucosamine
water-soluble; the more glycogen in a solution is,
is the monomer, and a dimer of N-acetylglucosamine is
the faster energy can be released.
the repeating disaccharide.
o 2. When an organism needs energy quickly for
WHAT ROLE DO POLYSACCHARIDES PLAY IN THE
spontaneous reflexes, the enzyme glycogen
STRUCTURE OF CELL WALLS?
phosphorylase has more potential targets if there
are more branches. This allows quicker • Heteropolysaccharides are major components of
mobilization of glucose bacterial cell walls.
WHAT IS CHITIN? o They are also cross-linked by peptides in
prokaryotic cells walls.
o The repeating polysaccharide units are consist of
two residues held at β(1→4) like cellulose.
o Residues are N-acetyl-D-glucosamine and N-
acetylmuramic acid.
• N-Acetylmuramic acid is found only in prokaryotic cell
walls (therefore in ALL BACTERIA); does not occur in
eukaryotic cell walls.

• Chitin: polysaccharide similar to cellulose in both

structure and function.
o Linear homopolysaccharide with all residues
linked in β(1→4) glycosidic bonds
• Differ from cellulose in the monomeric unit.
o cellulose: β-D-glucose
o chitin: N-acetyl-β-D-glucosamine

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BIOCHEMISTRY FIRST SEMESTER
LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022
CARBOHYDRATES AND GLYCOBIOLOGY

The structure of the peptidoglycan of the bacterial cell

wall of Staphylococcus aureus. (a) The repeating
disaccharide. (b) The repeating disaccharide with the
tetrapeptide side chain (shown in red). (c) Adding the
pentaglycine cross-links (shown in red). (d) Schematic
diagram of the peptidoglycan. The sugars are the larger
spheres. The red spheres are the amino acid residues of
the tetrapeptide, and the blue spheres are the glycine
residues of the pentapeptide.
• Plant cell walls consist largely of cellulose.
• Pectin, another component of plant cell walls, is
composed mostly of D-galacturonic acid (a derivative
of galactose) residues.
o Extracted from plants; used as a gelling agent in
yogurt fruit preserves, jams and jellies
• Lignin (L. lignum, “wood”) a nonpolysaccharide
component of plant cells walls; a polymer of coniferyl
alcohol, very tough and durable
o Actually not a polysaccharide but it is interesting
to know about this. When you are chopping wood,
it’s hard not because of cellulose but because of
lignin.
DO POLYSACCHARIDES PLAY ANY SPECIFIC
ROLES IN CONNECTIVE TISSUES
• Glycosaminoglycans: polysaccharide based on a
disaccharide in which one of the sugars is
o An amino sugar
o One of the sugars has a negative charge because
of a sulfate or a carboxyl group
• Involved in a wide variety of cellular function and
tissue.
o Heparin: a natural anticoagulant that prevents
blood clots
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BIOCHEMISTRY FIRST SEMESTER
LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022
CARBOHYDRATES AND GLYCOBIOLOGY
o Hyaluronic acid: a component of vitreous humor
of the eye and the lubricating fluid of the joints
o Chondroitin sulfates and keratan sulfate:
component of connective tissues
o Glucosamine sulfate and chondroitin sulfate:
OTC drugs that help repair damaged cartilage

Glycosaminoglycans, which are formed from repeating

disaccharide units, often occur as components of the
proteoglycans.

*Each polymer is classified as a homopolysaccharide

(homo-) or heteropolysaccharide (hetero-). †The
abbreviated names for the peptidoglycan, agarose, and
hyaluronate repeating units indicate that the polymer
contains repeats of this disaccharide unit. For example, in
peptidoglycan, the GlcNAc of one disaccharide unit is
(1n4)-linked to the first residue of the next disaccharide
unit.

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BIOCHEMISTRY FIRST SEMESTER
LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022
CARBOHYDRATES AND GLYCOBIOLOGY
GLYCOCONJUGATES: PROTEOGLYCANS,
GLYCOPROTEINS, AND GLYCOLIPIDS
WHAT ARE GLYCOCONJUGATES?
• Aside from being energy storage and structural
materials, sugars are also information carriers:
o They serve as destination labels for some
proteins
o They serve as mediator of specific cell-cell
interaction and interaction between cells and
extracellular matrix
• Other roles of specific carbohydratecontaining
molecules include The transmembrane proteoglycans. The four
o cell-cell recognition syndecans in the center are full-time proteoglycans that
o cell adhesion are usually substituted with heparan sulfate chains (dark
o cell migration blue) toward their N termini. Syndecans-1 and -3
o blood clotting sometimes possess additional chondroitin sulfate chains
o immune response, (pink). The melanoma chondroitin sulfate
• When an informational carbohydrate is covalently proteoglycan/NG2 (green) has one chondroitin sulfate
bonded to a protein or lipid, it forms a chain and is also a full-time proteoglycan. The remainder
glycoconjugate. are part-time proteoglycans. The alternately spliced
WHAT ARE THE DIFFERENT GLYCOCONJUGATES? extracellular segment of CD44 may bear one heparan
• Glycoproteins: have one or several sulfate chain. Neuropilin-1 and betaglycan can be
oligosaccharides covalently joined to a protein. substituted with either heparan or chondroitin/ dermatan
o The oligosaccharides have various complexity sulfate (purple)
depending on the molecule. • Proteoglycans: macromolecules of the cell surface
o Outside cell: on the outer face of the plasma of extracellular matrix, a type of glycoprotein
membrane, in the extracellular matrix, and blood o Unique from other glycoproteins because of
o Inside cell: Golgi complexes, secretory granules, glycosaminoglycan.
lysosomes o One or more glycosaminoglycan chains are
• Highly rich in information; forms specific sites for joined covalently to a membrane protein
recognition and high-affinity binding by other proteins. o Glycosaminoglycan moiety of the proteoglycan
dominates the structure; often the main site of
biological activity
▪ Moiety = is the part of a specific structure
o Major components of connective tissues such as
cartilage

Carbohydrates present in the plasma membrane as short,

sometimes branched, chains of sugars attached either to
exterior peripheral proteins (forming glycoproteins) or to
the polar ends of phospholipid molecules in the outer lipid
layer (forming glycolipids).
• Glycolipids: membrane lipids in which the
hydrophilic head groups are oligosaccharide
o Act as specific site for recognition by
carbohydrate-binding proteins.

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BIOCHEMISTRY FIRST SEMESTER
LECTURE | CHRISTIAN JOHN CAPIRIG, MD | MIDTERM A.Y. 2021 - 2022
CARBOHYDRATES AND GLYCOBIOLOGY
o Gangliosides are specific type of glycolipid and o N-Acetylgalactosamine is found at the
the carbohydrate moieties are available for signal nonreducing end of the oligosaccharide in the
transduction. type-A blood-group antigen
o In type-B blood, α-D-galactose takes the place of
N-acetylgalactosamine
o In type-O blood, neither of these terminal
residues is present
o In type-AB blood, both kinds of oligosaccharide
are present
• If a blood transfusion is attempted with incompatible
blood type, an antigen-antibody reaction takes place
o The antibodies on the recipient recognizes the
antigen specific for the introduced blood from the
donor.
o The characteristic oligosaccharide residues on
the introduced blood serve as the antigen
• Carbohydrates present in the plasma membrane as • A cross-linking reaction occurs; cells will clump
short, sometimes branched, chains of sugars together
attached either to exterior peripheral proteins • Wrong blood transfusion can result to life-threatening
(forming glycoproteins) or to the polar ends of severe reaction
phospholipid molecules in the outer lipid layer
(forming glycolipids).

CARBOHYDRATES AND THE IMMUNE RESPONSE

REFERENCES
• Campbell, M. K. & Farrell, S. O. (2009). Water: The
Solvent for Biochemical Reactions. In Biochemistry
6th Ed. p 37-64. Thomson Brooks/Cole, Belmont CA.
• Nelson, D. L., Lehninger, A. L., & Cox, M. M. (2008).
Lehninger principles of biochemistry. Macmillan.
• Rodwell, V . W., Bender, D. A., Botham, K. M.,
• Some of the most important examples of Kennelly, P . J., & Weil, P. A. (2018). Harper's
glycoproteins are involved in the immune response illustrated biochemistry. New York (NY): McGraw-Hill
(e.g., antibodies) Education.
o Antibodies bind to immobilize antigens that attack
the organism.
• Carbohydrates also play an important role as
antigenic determinants:
o portions of an foreign molecule that antibodies
recognize and to which they bind.
ABO BLOOD GROUPS
• The four blood groups are distinguished based on the
oligosaccharide portion of the glycoprotein on the
surface of red blood cells.
o In all blood types, L-fucose (6-deoxy-L-
galactose) is found

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