Comprehensive Biochemistry for Dentistry Textbook for Dental Students

586 23 Immunoglobulins

Immunoglobulin represent gamma-globulin fraction of plasma proteins. They
constitute around 20% of total plasma proteins. An immunoglobulin is composed of
about 80–96% of protein and 4–10% of oligosaccharides.

23.2 Structure of Immunoglobulin

23.2.1 E delman-Gally Model of Immunoglobulin

• Immunoglobulin molecule is Y shaped.
• Ig molecule is a heterotetramer composed of four polypeptide chains. Two heavy

chains represented as “H”-chain and two light chains represented as “L”-chain
are linked together by disulfide bonds. Immunoglobulin molecule can be written
as (H2 L2).
• Each H-chain is made up of 450 amino acid residues and each L-chain is com-
posed of 212 amino acid residues. Amino acid residues are arranged into specific
domains. Each domain contains around 110 amino acid residues. These domains
are interconnected by intra-chain disulfide bonds.
• The domains are broadly grouped into two categories as variable and constant
domains. In L-chain, the domain located toward N-terminal is called as variable
domain of light chain (VL), whereas the domain located toward C-terminal is
called as constant domain of light chain (CL). The sequence of amino acid resi-
dues is variable in variable domains.
• In H-chain, the domain located toward N-terminal is called as variable domain of
heavy chain (VH), and the domain on the C-terminal is called as constant domain of
heavy chain (CH). There are three constant regions in H-chain as CH1, CH2, and CH3.
The sequence of amino acid residues is comparatively stable in constant domains.
• Heavy chain characteristics.
–– On the basis of structure, five classes of H-chains have been identified among

humans. Their molecular weight is about 55,000. They are labeled as alpha
(α), gamma (γ), mu (μ), epsilon (ε), and delta (δ). Class of H-chain deter-
mines the type of immunoglobulin. Five types of immunoglobulins are named
as IgA, IgG, IgM, IgE, and IgD, respectively.
• Light chain characteristics.
–– On the basis of structure, two classes of L-chains have been identified among
humans. Their molecular weight is about 25,000. They are labeled as kappa
(k) and lambda (λ). A particular Ig molecule always possesses either kappa or
lambda class of light chain.
• Hinge region.
–– It is an inter-domain region on heavy chain. It is a highly variable region of
amino acid residues located in the central portion of H-chain. The hinge
region has predominantly cysteine and proline amino acid residues. It is sensi-
tive to enzymatic proteolysis.

23.2  Structure of Immunoglobulin 587

• Antigen-binding fragment (Fab).
–– It is the region of antibody which has specificity to antigen. It is composed of
two constant domains (CH and CL) and two variable domains (VH and VL)
toward N-terminal. Variable domains possess antigen-binding site called as
“paratope.” The antigen contains a specific site that attaches to the antibody
and is called as “epitope.” It is the antigen determinant.

• Fragment crystallization region (Fc).
–– This region is located toward the tail end of antibody. It is composed of three
constant domains (CH-2-4) in each H-chain. This region interacts with cell sur-
face receptors of immune cell. Fc region is helpful in the activation and regu-
lation of immune response.

• Enzymatic proteolysis of immunoglobulin.
–– Papain enzyme breaks immunoglobulin molecule into three similar-sized
fragments. Two fragments are named as “Fab,” and the third fragment is
named as “Fc.”
–– Pepsin enzyme cleavages Ig molecule below hinge region and yields a large
fragment called as F(ab)2 which can be further cleavaged into two Fab frag-
ments. Pepsin degrades Fc fragment completely.
–– Another enzyme, called as immunoglobulin-degrading enzyme from
Streptococcus pyogenes (IdeS), breaks IgG into F(ab)2 fragment as in
Fig. 23.1.

LICGHHATIN ANTIBODY
BINDING SITE
NH 2 S
NH 2 S HEAVY
CHAIN
HEAVY S S RVEARGIIAOBNLE
CHAIN S S COMPLIMENT BINDING SITE

CONSTANT S S S COOH COOH S S
REGION S
SS
HINGE SS
REGION S
S

S COOH
S

COOH
Fig. 23.1  Structure of Immunoglobulin

588 23 Immunoglobulins

23.3 C haracteristics of Individual Immunoglobulins

23.3.1 I mmunoglobulin A (IgA)

Features
• It is composed of two H-chains of class alpha (α) and two L-chains of class either

kappa or lambda class.
• IgA exists either as a single Y-shaped monomer or a dimer linked by J chain.
• Its molecular formula is α2k2 or α2λ2.
• Its molecular weight is between 150,000 and 500,000.
• Its carbohydrate content is 8%.
• IgA represents about 10–20% of total immunoglobulins.
• Its normal serum concentration is between 150 and 400 mg/dl.
• IgA is abundantly found in body secretions like saliva, sweat, tears, milk,

and gastrointestinal, nasal, and bronchial secretions. It is a highly predomi-
nant antibody in colostrum (first secretion from human breast after birth
of baby).

Functions
• It provides local immunity against pathogens. It is due to its high concentration

in body fluids. It prevents invasion of pathogens from the skin as well as from
mucosal surfaces. It binds with the antigens and destroys them.

23.3.2 Immunoglobulin G (IgG)

Features
• It is composed of two H-chains of class gamma (γ) and two L-chains of class

either kappa or lambda.
• It exists as a single Y-shaped monomer.
• Its molecular formula is γ2k2 or γ2λ2.
• Its molecular weight is 150,000.
• Its carbohydrate content is 3%.
• IgG represents about 70–80% of total immunoglobulins. It is the maximum

abundant immunoglobulin in body.
• Its normal serum concentration is between 600 and 1500 mg/dl.
• IgG is the unique antibody that can cross placental barrier. It provides immunity

to growing fetus. IgG can also cross pass through blood vessels.
• It is the predominant antibody that is produced in secondary immune response.

Functions
• IgG is the most predominant antibody against most of the bacterial and viral

infections.
• It provides humoral immunity against bacterial and viral infections.

23.3  Characteristics of Individual Immunoglobulins 589

23.3.3 Immunoglobulin M (IgM)

Features
• IgM is the largest antibody. It is composed of five Y-shaped monomeric units, so

IgM is a pentameric immunoglobulin.
• Each Y-shaped monomer is composed of two H-chains of class “mu” (μ) and two

L-chains of class either kappa or lambda.
• Its molecular formula is (μ2 k2)5 or (μ 2λ2)5.
• Its molecular weight is about 900,000.
• Its carbohydrate content is 12%.
• IgM represents about 7% of total immunoglobulins in the body.
• Its normal serum concentration is between 50 and 200 mg/dl.
• In IgM, individual monomers are linked together by J-shaped polypeptide chain.

This chain possesses high amount of aspartic acid and glutamic acid residues.
This polypeptide chain is highly elongated.
• Due to large size of IgM, it cannot pass through the blood vessels. It cannot cross
the placental barrier. It is the predominant antibody that circulates in the blood.
• It can bind with five antigenic sites simultaneously.

Functions
• IgM is the first-line antibody. It is the predominant antibody that is produced in

primary immune response.
• IgM constitutes naturally antibodies. They are the immunoglobulins of class IgM

produced by B lymphocytes in the absence of any antigenic exposure. Natural
antibodies are anti-A, anti-B, and anti-Rh antibodies.

23.3.4 I mmunoglobulin D (IgD)

Features
• IgD is composed of two H-chains of class delta (δ) and two L-chains of class

either kappa or lambda.
• It exists as a single Y-shaped monomer.
• Its molecular formula is δ2k2 or δ2λ2.
• Its molecular weight is 180,000.
• Its carbohydrate content is 15%.
• IgD represents about 0.5–2% of total immunoglobulins.
• Its normal serum concentration is around 5 mg/dl.
• It is the predominant antibody that is located on the cell surfaces of B lym-

phocytes along with another antibody IgM.

Functions
• Function of IgD is uncertain.
• IgD is helpful in the differentiation of B lymphocytes. IgD coats the surfaces of

B lymphocytes along with IgM.

590 23 Immunoglobulins

• IgD is necessary for activation of B lymphocytes.
• IgD stimulates mast cells and basophils to release antimicrobial substances. So

IgD provides local immunity in respiratory system.

23.3.5 Immunoglobulin E (IgE)

Features
• IgE is composed of two H-chains of class epsilon (ε) and two L-chains of class

either kappa or lambda.
• It exists as a single Y-shaped monomer.
• Its molecular formula is ε2k2 or ε2λ2.
• Its molecular weight is 190,000.
• Its carbohydrate content is 11%.
• IgE represents about 0.004% of total immunoglobulins.
• Its normal serum concentration is 0.02–0.05  mg/dl. It occurs in least

concentration.
• IgE is bound to Fc cell surface receptors on mast cells through its Fc region. The

IgE coats mast cells and is responsible for allergic response of host body. It is
called as “reaginic antibody.”

Functions

• Dual nature of IgE
–– IgE antibody binds with allergens through its Fab region. But IgE binds to
surface of mast cells through its Fc region.

• Protection against helminthic infection
–– IgE is primarily involved in defense against helminthic infection caused by
Schistosoma mansoni, Fasciola hepatica, and Trichinella spiralis parasites.

• Defense against Plasmodium
–– IgE has a role in immune response in Plasmodium parasite infection.

• Type-1 hypersensitivity
–– IgE is responsible for type-1 hypersensitivity. IgE interacts with allergens on
the surface of mast cells. The allergen-antibody complex induces degranula-
tion of mast cells. These granules release histamine, prostaglandins, and leu-
kotrienes. These substances are responsible for allergic manifestations in
body of the host. IgE is implicated in allergic asthma, allergic rhinitis, sinus-
itis, urticarial, and atopic dermatitis.

Suggested Readings 591

Suggested Readings

Charles J (2001) Immunobiology, 5th edn. Garland Publishing, Oxford
Edelman GM, Gally JA (1964) A model for the 7S antibody molecule. Available at: http://www.

pnas.org/content/51/5/846.full.pdf
Kirkham PM, Schroeder HW Jr (1994) Antibody structure and the evolution of immunoglobulin V

gene segments. Semin Immunol 6:347–360
Kleiner IS, Orten JM (1966) Biochemistry, 7th edn. Mosby publisher, St Louis
Latner AL (1975) Cantarow and Trumper. Clinical biochemistry, 7th edn. Saunders, Philadelphia
Mazur A, Harrow B (1971) Textbook of biochemistry, 10th edn. Saunders, Philadelphia
McGilvery RW (1983) Biochemistry-a functional approach, 3rd edn. Saunders, Philadelphia
Pier GB, Lyczak JB, Wetzler LM (2004) Immunology, infection, and immunity. ASM Press,

Washinton DC
Rawn JD (1989) Biochemistry. Neil Patterson Publsihers, Burlington, NC
Streyer L (1975) Biochemistry, 3rd edn. Freeman WH, New York
Swaminathan M (1981) Biochemistry for medical students, 1st edn. Geetha Publishers, Mysore
Thorpe WB, Bray HG, James HP (1970) Biochemsitry for medical students, 9th edn. Churchill,

London
Varley H (1969) Practical clinical biochemistry. WH Medical Books, London
Yudkin M, Offord K (1973) Comprehensive biochemistry. Longman, London

Part VI
Dental Biochemistry

Dental Biochemistry 24

24.1 I ntroduction

The teeth are the calcified tissues of the oral cavity which serve to masticate foods,
are helpful in speech, and have aesthetic function. A tooth is made up of calcified
tissues and vascular tissues. Calcified tissues cover crown and root portions of the
tooth. The calcified tissues are labeled as follows:

• Enamel (the hardest tissue of body and surrounds crown of tooth)
• Dentin (forms crown and root of tooth)
• Cementum (hard tissue that surrounds root of tooth)

Chemical composition of three layers is described separately as follows:

• Chemical composition of enamel
• Dentin
• Cementum

24.2 Enamel

Enamel is the outermost, avascular, nonliving, calcified and protective layer over the
crown of teeth.

Characteristics of Enamel
• Enamel is developed from the ectodermal layer.
• Enamel is the protective layer of the crown of teeth.
• Enamel is synthesized by ameloblasts.
• It is the hardest tissue of the body.
• It is minimally porous in nature.

© Springer Nature Singapore Pte Ltd. 2019 595
A. Gupta, Comprehensive Biochemistry for Dentistry,
https://doi.org/10.1007/978-981-13-1035-5_24

596 24  Dental Biochemistry

• Its color is yellowish white.
• Enamel thickness is maximum at cusps of molars and premolars (2–2.5 mm). Its

thickness is minimum at the neck region of the tooth.

24.2.1 C hemical Composition of Enamel

Enamel is composed of water and solids. These constituents of enamel layer are
explained as follows:

Water
• Water constitutes only 3% of weight of enamel.
• Water is present in loosely bound state in organic matrix and in hydroxyapatite

crystals.

Solids
Solids in the enamel are further sub-divided into organic solids and inorganic solids.
Each type of solid component of enamel is described below:

Organic Solids
• Organic solids form only 1% of the weight of tooth enamel.
• Organic solids are deposited by ameloblasts in developmental stage of tooth.
• In mature tooth, organic solids are present around enamel rods. Enamel rods are

the densely packed mass of hydroxyapatite crystals which are supportive units of
enamel of teeth.

Chemical nature of organic solid in enamel:
• Chemical structure of organic solids in the enamel is variable and it depends

on the stage of tooth development. it is described under two headings as
below:
–– Developmental enamel

Histological sectioning of developmental enamel shows that organic matrix
of enamel resembles to keratin. Nevertheless, analysis of amino acid com-
position of mature enamel does not prove keratin nature of organic matrix.
–– Mature enamel
Analysis of proteins in mature enamel shows high proportion of amino
acids like serine, glycine, and glutamic acid in organic matrix of enamel.

X-ray diffraction studies of mature enamel show the presence of beta-­pleated
structure of proteins in enamel matrix. Organic solids in enamel contains predomi-
nantly proteins like amelogenin, and enamelin. The important characteristics of
these proteins are described below:

24.2 Enamel 597

Enamel Proteins
Amelogenin

• It is the chief structural protein of enamel.

• Amelogenin is secreted by ameloblasts in developmental stage. It is the chief

protein of extracellular matrix of enamel. It constitutes around 90–95% of all

enamel proteins.
• Amelogenin is rich in serine, proline, leucine, and histidine amino acid

residues.
• Amelogenin residues aggregate to form nanoaggregates. They provide nucleus

to initiate crystallization. It regulates growth and alignment of apatite crystals.

Enamelin
• Enamelin is another structural protein of enamel.
• It represents only 1–2% of total enamel proteins.
• Enamelin is necessary for normal synthesis of enamel. Enamel synthesis is regu-

lated by ENAM gene. Any mutation in ENAM gene results in a disorder called
as enamel hypoplasia (amelogenesis imperfecta).
• Enamelin controls the formation of amelogenin nanoaggregates.

Inorganic Solids

• Inorganic solids constitute chief structural and supportive components of tooth

enamel. They constitute around 96% of the weight of enamel.
• Calcium and phosphorous are the chief minerals in inorganic components of

enamel. These minerals exist in crystalline form which are called as apatite
crystals. Apatite crystals are associated with hydroxyl ions and are named as
hydroxyapatite crystals.

• These crystals are highly organized and tightly packed to form enamel rods.
• Hydroxyapatite crystals

–– Hydroxyapatite crystals are hexagonal shaped.

–– Hydroxyapatite crystals are made up of calcium phosphate (apatite crystals)
with hydroxyl ions. Their formula is Ca10(PO4)6 X2.

–– Width of crystals is 60 nm and thickness is 30 nm.

–– Calcium ions are arranged to form a hexagon. Inside a hexagon, three calcium

ions are arranged to form a triangle. Two such triangles are placed parallel to

each other inside a hexagon.

–– Phosphate ions are arranged in two tetrahedrons in between two calcium ions.

One tetrahedron is made up of one phosphorous and four oxygen atoms.

–– Two hydroxyl ions are located inside calcium triangles within hexagon.
Fluoride ions can replace hydroxyl ions to form “fluoroapatite crystals.”
These crystals are less soluble in acids and more stable than hydroxyapatite
crystals. Fluoroapatite crystals render enamel resistant to dental caries.

598 24  Dental Biochemistry

Trace Minerals in Inorganic Solids of Enamel
• Minerals like fluoride, zinc, chloride, and selenium are present in higher concen-

tration on the surface enamel than deeper layers of enamel.
• Minerals like sodium, magnesium, and carbonates are present in higher concen-

tration in deeper layer of enamel than its surface layer.

24.3 Dentine

Dentine is the inner, calcified, avascular, and sensitive layer of teeth that forms
crown and root of teeth.

Characteristics of Dentine
• Dentine is developed from mesodermal layer.
• It is yellow in color.
• Dentine is synthesized by odontoblasts. They are large sized columnar cells and

are packed between dentine and pulp in the tooth. These cells form dentine
through the process of dentinogenesis.
• Hardness property of dentine is higher than the bone, lesser than enamel, and
almost equal to cementum.
• Inner to Dentine, pulp cavity is present in the tooth. This cavity contains highly
vascular soft tissues. It is richly innervated.

24.3.1 Chemical Composition of Dentine

Dentine is made up of water and solids. Solids are further grouped into inorganic
solids and organic solids as follows:

Water
• Water represents nearly 10% of weight of dentine.
• Water is present in bound state in organic matrix and in hydroxyapatite crystals

in dentine.

Organic solids
• Organic solids constitute around 20% of weight of dentine.
• Organic solids are further grouped into two categories as dentine proteins

and ground substance which are explained below as:
–– Dentine proteins are the chief organic elements of dentine. The collagen

and sialophosphoprotein are the predominant dentine proteins. Their
characteristics are described below:
Collagen
Collagen represents about 90% of the total organic solids of dentine. It is an
important structural protein of dentine.

24.4 Cementum 599

Dentine contains type-I collagen protein. It is made up of two alpha-1
chains and one alpha-2 chain. These three chains are right-handed helically
coiled to form a triple helix protein structure.

Each chain contains 1000 amino acids residues. Glycine residues consti-
tute 30% of total amino acid residues in each chain. Proline and lysine together
represent another 30% proportion of amino acid residues in each chain.
Other dentine proteins
Dentin sialophosphoprotein
It is secreted by odontoblasts in pulp of teeth and osteoblasts in bone tissues.
This protein is essential for calcification of organic matrix of dentine.

Dentine sialophosphoprotein is a precursor molecule that produces three
dentine proteins as dentin sialoprotein, dentin glycoprotein, and dentin
phosphoprotein.

Three proteins constitute chief non-collagen proteins of dentine. They con-
trol calcification of dentine.
–– Ground substance
Ground substance constitutes about 10% of the total organic solids of dentine.
It is an amorphous gel-like substance in extracellular matrix in dentine.

It is made up of glycosaminoglycans (GAG) and peptides. The prominent
GAGs are chondroitin sulfate moieties. They are linked with short peptides to
form glycoproteins.

Inorganic Solids
• Inorganic solids represent around 70% of the weight of dentine.
• They are mainly calcium and phosphate ions which are crystalized in form of

hydroxyapatite crystals as in enamel.
• Size of hydroxyapatite crystals in dentine is smaller than enamel. It is 1/10 of the

size in enamel.

24.4 C ementum

It is a calcified and protective layer on root of the teeth.

Characteristics of Cementum
• It is yellowish in color and mildly softer in comparison to dentine.
• Primary cementum is present on coronal 1/3 of root. It is acellular. Secondary

cementum is present on middle 1/3 and apical 1/3 of root. It is cellular in nature.

24.4.1 C hemical Composition of Cementum

Water
• Water represents 10% of weight of cementum.

600 24  Dental Biochemistry

Organic Solids
• It forms about 25% of weight of cementum.
• It is mainly composed of type-I collagen fibers.

Inorganic Solids
• It forms about 65% of the weight of cementum.
• It is in the form of hydroxyapatite crystals.

24.5 Biochemical Basis of Dental Caries

24.5.1 Dental Caries

Definition
Dental caries is defined as a microbial, invasive, and progressive disorder char-
acterized by demineralization of inorganic components and proteolysis of
organic components of teeth.

24.5.2 R ole of Biochemical Compounds Involved in Dental Caries

Role of Sucrose and Lactic Acid
• Streptococcus mutans is a gram-positive bacterium. It is the predominant bacte-

ria of the oral cavity. It is present in dental plaque.
• S. mutans is the acidogenic bacteria. It has glucansucrase enzyme. This enzyme

can split dietary sucrose into glucose and fructose. Glucose is converted into
lactic acid through glycolysis pathway.
• Lactic acid decreases pH at the interface dental plaque and enamel surface. This
activity favors demineralization of hydroxyapatite crystals and initiation of
dental caries.

Role of Extracellular Polysaccharides
• S. mutans have remarkable ability to synthesize extracellular polysaccharides

(EPS) from sucrose.
• Bacteria can decompose sucrose into glucose and fructose by glucansucrase

enzyme. S. mutans has enzyme glucosyltransferase which catalyzes polymeriza-
tion of glucose into glucans. Another enzyme fructosyltransferase catalyzes con-
version of fructose into long chain polysaccharides called as fructans.
• Glucans and fructans are extracellular polysaccharides (mucilaginous carbohy-
drates) which are clearly and significantly implicated in initiation and progres-
sion of dental caries.
• EPS has the following impacts as follows:
–– EPS promotes adherence of bacteria to enamel pellicle and dental plaque.
–– EPS is insoluble in water. It serves as barrier between enamel and oral envi-

ronment. It retains acids in close contact with enamel.
–– EPS helps to raise thickness of plaque.

24.5  Biochemical Basis of Dental Caries 601

The role of sucrose, lactic acid, and EPS has been postulated in acidogenic
theory of dental caries. It was proposed by W. D. Miller in 1890.

Theory states that dental caries involves decalcification of hard tissues of teeth
owing to acids produced by fermentation of dietary sucrose by bacteria.

24.5.3 Fluoride as Anticaries Agent

Fluorine is electronegative element and exists in nature as fluoride in bound form.
Fluoride is present in water, tea, and fish. It is absorbed from intestinal mucosa and
enters circulation. Fluoride is concentrated into calcified tissues of body during
mineralization of bones and teeth.

Fluoride is incorporated into hydroxyapatite crystals during development stage.
It replaces hydroxyl ions, and resultant crystals are termed as fluoroapatite
crystals.

In enamel, fluoride concentration is higher in superficial layer of enamel than
deeper layer.

In dentine and cementum, its concentration is higher in deeper layers. Dentine
and cementum store greater amount of fluoride than enamel.

Mechanism of Action of Fluoride
1. Fluoroapatite Crystals

• Apatite crystals are surrounded by hydration shell (layer of adsorbed water).
Fluoride ions pass through hydration shell and combines with calcium ions to
form a thin layer of calcium fluoride. It protects deeper apatite crystals. Later
on, surface fluoride ions are incorporated into crystal lattice. It replaces
hydroxyl ions to form fluoroapatite crystals.

• Fluoroapatite crystals are resistant to acid attack. Their solubility in acid is
less to that of hydroxyapatite crystals. Fluoroapatite crystals have higher dis-
solution time than hydroxyapatite crystals. Higher dissolution time promotes
remineralization of enamel surface.

2 . Inhibition of Enolase Enzyme
• Enolase enzyme catalyzes conversion of phosphoenolpyruvate into pyruvate.
Fluoride ions inhibit enolase enzyme in bacteria. Fluoride ions intercept
g­ lucose metabolism of bacteria. Overall, fluoride ions prevent formation of
lactic acid.

24.5.4 Salivary Proteins in Dental Caries

Dental caries is a progressive disorder caused by multiple factors. Salivary proteins
have protective and diagnostic roles in dental caries.

Saliva contains lactoferrin, immunoglobulins, lysozymes, albumin, and mucin as
important proteins. Salivary mucin and glycoproteins rich in proline are helpful in
formation of a coat over enamel surface. These proteins protect enamel surfaces of
teeth from attrition and abrasion. Salivary proteins protect from demineralization of

602 24  Dental Biochemistry

enamel surfaces. Proteins retain calcium and phosphate ions in contact with enamel
surfaces and are helpful in remineralization.

Immunoglobulin A is the predominant antibacterial protein of saliva. It is synthe-
sized by plasma cells and secreted in saliva. IgA prevents proliferation of cariogenic
organisms and decreases their colonization in plaque.

Mucin is a glycoprotein and main salivary protein. Mucin plays multiple roles in
oral cavity. Mucin forms a sticking coat on the surfaces of teeth. It protects teeth
from acid attack by minimizing contact with enamel surface. Mucin decreases bac-
terial colonization and adherence on tooth surfaces.

Proline-rich proteins in saliva are basic proteins. They have affinity to hydroxy-
apatite crystals. These proteins help to neutralize acid produced by S. mutans. These
proteins chelate free calcium ions in saliva and help in remineralization of enamel.

C-reactive protein is an acute phase protein. It has a diagnostic role in dental car-
ies and periodontal diseases. It is synthesized in the liver. It is secreted by salivary
glands in the oral cavity. It is an important biomarker in dental diseases.

24.6 Chemical Composition of Saliva

Saliva is a colorless viscous fluid secreted by salivary glands.

Chemical Composition
Saliva contains 99.5% water and 0.5% solids.

Solids
Organic Solids
Organic solids can further be subdivided into following substances as:

• Enzymes
–– Salivary amylase
Salivary amylase is a calcium-dependent metalloenzyme. It is also called as
alpha-amylase or ptyalin. It splits starch into maltose and dextrin.
–– Maltase
Maltase is a disaccharide-splitting enzyme. It cleavages maltose into two mol-
ecules of glucose.
–– Lingual lipase
Lingual lipase is secreted by Ebner’s gland on the dorsum of the tongue. It is
an acidic lipase. It hydrolyzes triglycerides into mono- and diglycerides with
release of free fatty acids.
–– Lysozymes
Lysozyme is an antibacterial enzyme. It hydrolyzes 1,4-glycosidic bond
between N-acetylmuramic acid and N-acetyl-D-glucosamine in peptidoglycans
of bacterial cell wall. Lysozymes destroy bacteria in saliva.
–– Carbonic anhydrase
Carbonic anhydrase helps to maintain pH homeostasis in the oral cavity.
Saliva has buffering activity.
–– Kallikrein

24.6  Chemical Composition of Saliva 603

Kallikrein is a proteolytic enzyme. It is secreted by acinar cells of salivary
glands. Kallikrein splits kininogens into bradykinin (vasodilator).
–– Lactoperoxidase
Lactoperoxidase belongs to peroxide enzyme. It catalyzes oxidation of thio-
cyanates, bromides, and iodides. It is a strong antibacterial enzyme. It pro-
vides innate immunity against pathogens in oral cavity.

• Proteins
–– Immunoglobulin-A
IgA is an antibody. It is synthesized by plasma cells and secreted into saliva
by acinar cells of salivary glands. IgA provides local immunity in oral cavity.
–– Proline-rich proteins
Proline-rich proteins are intrinsic disordered proteins. These proteins are devoid
of regular three-dimensional structure. These proteins contain multiple short
repeats of proline-rich sequences. Proline-rich proteins in saliva help to bind
calcium to enamel surface and have antimicrobial property, for example, PRB4.
–– Lactoferrin
Lactoferrin is an iron-binding conjugated protein. It belongs to the transferrin
family. Lactoferrin is secreted by salivary glands. It helps to regulate
concentration of free iron in the blood and secretion of the body. It is also a
part of the innate immune system. Lactoferrin sequesters free iron in saliva.
Iron is a growth factor of pathogens. Therefore, lactoferrin helps to kill
pathogens. Its another antibacterial property is that it can attach to receptors
located on microbial cell wall. The ferric iron in lactoferrin catalyzes oxidation
of lipids and polysaccharides in bacterial cell wall.
–– Mucin
Mucin is a glycoprotein. It is the chief organic component of mucus (viscous
secretion that covers oral mucous membranes) of saliva. Mucin helps in the
lubrication of mucosa, prevents from chemical injury, and acts as a barrier
between pathogens and mucosa.
–– Epidermal growth factor
Epidermal growth factor in saliva is a protein. It is made up of 53 amino acid
residues. EGF helps in growth of cells, proliferation, and differentiation.
–– Albumin
Albumin is an important protein in saliva. Salivary albumin functions as pro-
tein buffer in saliva. It also has a diagnostic role in the oral cancerous lesions.
–– Carbohydrates
Saliva does not contain carbohydrates in normal and healthy individuals.
However, in diabetes mellitus, glucose is present in saliva.
–– Nonprotein nitrogenous substances
Saliva excretes nonprotein nitrogenous substances like xanthine, hypoxan-
thine, creatinine, urea, and uric acid.

Inorganic Solids
• Saliva contains cations like Na+, K+, Ca++, Mg++, and anions like Cl−, HCO3−, F−.

Saliva also contains oxygen, carbon dioxide, and nitrogen gases.

604 24  Dental Biochemistry

24.7 Periodontal Diseases and Immunity

Oral cavity harbors hundreds of microbial species. Streptococcus species are impli-
cated in the formation of plaque on teeth surfaces. Poor oral hygiene causes a shift
in the nature of microbes in dental plaque with preponderance of facultative anaer-
obes and gram-negative microbes. These organisms release endotoxins in gingival
sulcus which activates acquired immune system. Antigens are recognized and pre-
sented by antigen-presenting cells to lymphocytes. Antigen-presenting cells release
pro-inflammatory cytokines like interleukin-1, IL-6, and alpha-tumor necrosis fac-
tor to activate cytotoxic T cells. These lymphocytes phagocytose the pathogens.
Endotoxins and pro-inflammatory cytokines induce vascular changes in the blood
circulation of periodontium. There is an increase in capillary permeability in the
vasculature of periodontium. It leads to emigration of neutrophils, macrophages,
and monocytes to the site of junctional epithelium and crevicular fluid in gingival
sulcus.

There is formation of inflammatory exudate in gingival sulcus. These changes
are associated with breakdown of collagen fibers, junctional epithelium, and con-
nective tissues surrounding the root of the teeth. As the inflammation progresses, B
lymphocytes appear at the site of inflammation. The junctional epithelium migrates
apically, and it leads to formation of periodontal pocket.

Poor oral hygiene associated with bacterial invasion of periodontal tissues trig-
gers immunogenic inflammation of host oral tissues which damage periodontium.

Suggested Readings

Bhasker SN (ed) (2005) Orban’s oral histology and embryolog. Elsevier, New Delhi
Van Nieuw Amerongen A, Bolscher JG, Veerman EC (2004) Salivary proteins: protective and

diagnostic value in cariology? Caries Res 38:247–253