This document discusses calcium metabolism and regulation. It covers the distribution of calcium in the body, daily requirements, dietary sources, and functions of calcium. The key roles of calcium are in bone and teeth formation, muscle contraction, nerve conduction, blood coagulation, and enzyme activation. Calcium levels are tightly regulated by parathyroid hormone, calcitriol (vitamin D), and calcitonin which act on bone, kidneys, and intestines. Absorption of calcium depends on factors like vitamin D, acidity, proteins and absorption can be decreased by things like phytic acid, oxalates, and high phosphate levels.

2. CALCIUM METABOLISM
Dr Milind rajan
1ST YEAR
DEPT-PEDIATRICDENTISTRY
COORGINSTITUTEOFDENTALSCIENCES
ROLE OF PROTEINS ANDLIPIDS
TRACE ELEMENTSINCARIOLOGY

3. CONTENTS
 Introduction
 History
 Distribution
 Daily requirements
 Dietary sources
 Functions
 Factors controlling absorption
 Hormonal control
 Other hormones affecting metabolism
 Proteins

4.  Types of protiens
 Structure
 phosphoryalation
 Daily requirements
 Dietary sources
 Protiens and oral health
 Lipids
• Trace elements in cariology
• ESSENTIAL TRACE ELEMENTS
• TRACE ELEMENTS AND NUTRITION
• FUNCTION OF TRACE ELEMENTS
• TRACE ELEMENTS AND CARCINOGENESIS
• CONCLUSION
• REFERENCES

5. INTRODUCTION
• METABOLISM
It is defined as the chemical and physical process in an organism by which protoplasm
is produced , sustained , and then decomposed to make energy available.
It is the biochemical modification of chemical compounds in living organisms and
cells that includes the biosynthesis of complex organic molecules (anabolism) and
their breakdown (catabolism).

6. Classification of minerals according to their essentiality
Major elements Minor elements
Calcium Iron
Magnesium
Phosphorous
Sodium
Potassium
Chloride
Sulfur
Iodine
Copper
Manganese
Zinc
Molybdenum
Selenium
Fluoride

7. CALCIUM
• Soft grey alkaline earth metal
• Symbol ‘Ca’
• Atomic Number 20
• Atomic weight 40 g/mol
• Single oxidation state +2
• Fifth most abundant element in Earth´s
crust
• Essential for living organisms

8. CALCIUM OCCURRENCE
In nature
• Does not exist freely
• Occurs mostly in soil systems as limestone (CaCO3), gypsum (CaSO4*2H2O) &
fluorite (CaF2)
In the body
• The most abundant mineral
• Average adult body contains approx 1 kg

9. DISTRIBUTION

10. DISTRIBUTION
• 2% of body weight
 99% in bones
 1% in body fluids
• Plasma (Extracellular fluid)
– 2.25 – 2.75 mmol/l
• Cell (Intracellular fluid)
– 10mmol/l

11. PLASMA CALCIUM
Diffusible
• 50% Ca2+ ionized
• 10% combined with anions (citrate, phosphate) – non-dissociated
Nondiffusible
• 40% combined with plasma proteins

12. CALCIUM PHOSPHATE RATIO
• Calcium : Phosphate ratio normally is 2:1.
• Increase in plasma calcium levels causes corresponding decrease in absorption of phosphate.
• This ratio is always constant.
The serum level of calcium is closely regulated with normal total calcium of 9-10.5 mg/dL and
normal ionized calcium of 4.5-5.6 mg/dL. Serum Phosphate levels
• Children - 4 to 7 mg/dL
• Adults - 3 to 4.5 mg/dL

13. Calcium metabolism
• Most abundant mineral in the human body
• Total Calcium in the human body is about 1 to 1.5 kg, 99% of which
is seen in bone together with phosphate
• Small amounts in soft tissue & 1% in extracellular fluid
• Dietary Sources of calcium:
• Milk is a good source for calcium
• Egg, fish, cheese, beans, lentils, nuts, cabbage and vegetables are
sources for calcium

14. • Calcium in plasma is of 3 types
• Ionized or free or unbound calcium:
• In blood, 50% of plasma calcium is free & is metabolically active
• It is required for the maintenance of nerve function, membrane
permeability, muscle contraction and hormone secretion
• Bound calcium: 40% of plasma calcium is bound to protein mostly albumin
• These two forms are diffusible from blood to tissues

15. RECOMMENDED CALCIUM INTAKE
Age Amount of calcium
Infants
Birth to six months
6 months to 1 year
400mg
600mg
Children / young adults
1 – 10 years
11 – 24 years
800 – 1200mg
1200 – 1500mg

16. Adult women
Pregnant and lactating Over
65 yrs old
1200 – 1500mg
1500mg
Adult men
25 – 64 yrs old
Over 65 yrs old
1000mg
1500mg
RECOMMENDED CALCIUM INTAKE

17. Daily requirement of calcium
• Adults
• Children’s
• Pregnancy & lactation
= 500 mg/day
= 1200 mg/day
= 1500 mg/day
• After the age of 50, tendency for osteoporosis, prevented by increased
calcium (1500 mg/day) & vitamin D (20 μg/day)
• Body distribution of Calcium:
• About 99% of calcium is found in bones
• It exists as carbonate or phosphate of calcium
• About 0.5% in soft tissue and 0.1% in extracellular fluid

18. • Complexed calcium:
• 10% of plasma calcium is complexed with anions including bicarbonate,
phosphate, lactate & citrate
• All the three forms of calcium in plasma remain in equilibrium with each
other
• Normal Range:
• The normal level of plasma calcium is 9-11mg/dl

19. Absorption
• Mechanism of absorption of calcium:
• Calcium is taken in the diet as calcium phosphate, carbonate & tartarate
• About 40% of dietary calcium is absorbed from the gut
• Absorption occurs form the first & second part of duodenum
• Absorbed against a concentration gradient & requires energy

20. • Requires a carrier protein, helped by calcium-dependent ATPase
• 400 mg is excreted in stool & 100 mg is excreted through urine
• Two mechanisms for absorption of calcium:
• Simple diffusion
• An active transport - Process involving energy & Ca2+ pump
• Both processes require 1, 25 DHCC (Calcitriol) which regulates the synthesis
of Ca-binding proteins & transport

21. Factors causing increased absorption
• Vitamin D:
• Calcitriol induces the synthesis of carrier protein (Calbindin) in the
intestinal epithelial cells & facilitates the absorption of calcium
• Parathyroid hormone:
• It increases calcium transport from the intestinal cells by enhancing
1α-hydroxylase activity

22. • Acidity:
• Favors calcium absorption because the Ca-salts, particularly PO4 &
carbonates are quite soluble in acidic solutions
• In alkaline medium, the absorption of calcium is lowered due to the
formation of insoluble tricalcium PO4
• High protein diet:
• A high protein diet favors calcium absorption
• If the protein content is low, only 5% may be absorbed

23. • Amino acids:
• Lysine & arginine increases calcium absorption
• Amino acids increase the solubility of Ca-salts & thus its absorption
• Sugars and organic acids:
• Organic acids produced by microbial fermentation of sugars in the gut,
increases the solubility of Ca-salts & increases their absorption
• Citric acid may also increase the absorption of calcium

24. Factors causing decreased absorption
• Phytic acid: Cereals contain phytic acid (Inositol hexaphosphate) forms
insoluble Ca-salts & decreases the absorption
• Oxalates: Present in some leafy vegetables, causes formation of insoluble
calcium oxalates
• Fibres: Excess of fibres in the diet interferes with the absorption

25. • Malabsorption syndromes:
• Causing formation of insoluble calcium salt of fatty acid
• Glucocorticoids:
• Diminishes intestinal transport of calcium
• Phosphate:
• High phosphate content will cause precipitation as calcium phosphate
• Magnesium: High content of Mg decreases the absorption
• Ca: P Ratio: 2:1

26. Biochemical functions
• Development of bones and teeth:
• Bone is regarded as a mineralized connective tissue
• Bones also act as reservoir for calcium
• The bulk quantity of calcium is used for bone and teeth formation
• Osteoblasts induce bone deposition and osteoclasts produce
demineralization

27. • Muscles:
• Calcium mediates excitation & contraction of muscles
• C2+ interacts with troponin C to trigger muscle contraction
• Calcium activates ATPase, increases action of actin and myosin and
facilitates excitation-contraction coupling.
• Calcium decreases neuromuscular irritability.
• Calcium deficiency causes tetany

28. • Nerve conduction:
• It is necessary for transmission of nerve impulses
• Blood coagulation:
• Calcium is known as factor IV in blood coagulation process
• Prothrombin contains γ-carboxyglutamate residues which are chelated by
Ca2+ during the thrombin formation
• Calcium is required for release of certain hormones from cells include
insulin, parathyroid hormone, calcitonin, vasopressin

29. • Activation of enzymes:
• Calmodulin is a calcium binding regulatory protein, with a molecular
weight of 17,000 Daltons
• Calmodulin can bind with 4 calcium ions
• Calcium binding leads to activation of enzymes
• Calmodulin is part of various regulatory kinases
• Enzymes activated by Ca2+ include pancreatic lipase, enzymes of
coagulation pathway, and rennin

30. • Second messenger:
• Calcium and cAMP are second messengers for hormones e.g.
epinephrine in liver glycogenolysis
• Calcium serves as a third messenger for some hormones e.g, ADH
acts through cAMP and then Ca2+
• Myocardium:
• Ca2+ prolongs systole
• In hypercalcemia, cardiac arrest is seen in systole

31. Regulation of plasma calcium level
• Dependent on the function of 3 main organs
• Bone
• Kidney
• Intestine
• 3 main hormones
• Calcitriol
• Parathyroid hormone
• Calcitonin
• Also by GH, glucocorticoids, estrogens, testosterone & thyroid

32. Regulation of plasma calcium level by Calcitriol
• Role of calcitriol on bone:
• In osteoblasts of bone, calcitriol stimulates calcium uptake for
deposition as calcium phosphate
• Calcitriol is essential for bone formation
• Calcitriol along with parathyroid hormone increases the mobilization
of calcium and phosphate from the bone
• Causes elevation in the plasma calcium and phosphate

33. Role of calcitriol on kidneys
• Calcitriol minimizing the excretion of Ca2+ & phosphate by decreasing their
excretion & enhancing reabsorption
• Role of calcitriol on intestine:
• Calcitriol increases the intestinal absorption of Ca2+ & phosphate
• Calcitriol binds with a cytosolic receptor to form a calcitriol-receptor complex
• Complex interacts with DNA leading to the synthesis of a specific calcium
binding protein
• This protein increases calcium uptake by intestine

34. Regulation by parathyroid hormone (PTH)
• Parathyroid hormone (PTH) is secreted by two pairs of parathyroid glands
• Parathyroid hormone (mol. wt. 95,000) is a single chain polypeptide,
containing 84 amino acids
• It is originally synthesized as prepro PTH, whch is degraded to proPTH and,
finally, to active PTH
• The rate of formation & secretion of PTH are promoted by low Ca2+
concentration

36. Mechanism of action of PTH
• Action on the bone:
• PTH causes decalcification or demineralization of bone, a process carried
out by osteoclasts.
• This is brought out by pyrophosphatase & collagenase
• These enzymes result in bone resorption
• Demineralization ultimately leads to an increase in the blood Ca2+ level

37. Action on the kidney
• PTH increases the Ca2+ reabsorption by kidney tubules
• It most rapid action of PTH to elevate blood Ca2+ levels
• PTH promotes the production of calcitriol (1,25 DHCC) in the kidney by
stimulating 1- hydroxyaltion of 25-hydroxycholecalciferol
• Action on the intestine:
• It increases the intestinal absorption of Ca2+ by promoting the synthesis
of calcitriol

38. Calcitonin
• Calcitonin is a peptide containing 32 amino acids
• lt is secreted by parafollicular cells of thyroid gland
• The action of CT on calcium is antagonistic to that of PTH
• Calcitonin promotes calcification by increasing the activity of osteoblasts
• Calcitonin decreases bone resorption & increases the excretion of Ca2+
into urine
• Calcitonin has a decreasing influence on blood calcium

39. Calcitonin, calcitriol &PTHact together

40. • Serum Proteins:
• In hypoalbuminemia, total calcium is decreased
• In such cases, the metabolically active ionized Ca2+ is normal & so there will
be no deficiency manifestations
• Alkalosis and Acidosis: Alkalosis favors binding of Ca2+ with proteins, with
consequent lowering of ionized Ca2+
• Total calcium is normal, but Ca2+ deficiency may be manifested
• Acidosis favors ionization of Ca2+
• The renal threshold for calcium in blood is 10 mg/dl

41. Hypercalcemia
• The serum Ca2+ level >11 mg/dl is called as Hypercalcemia
• Causes:
• Hyperparathyroidism:
• Decrease in serum phosphate (due to increased renal losses) and increase
in ALP activity are found in hyperparathyroidism
• Urinary excretion of Ca2+ & P resulting in formation of urinary calculi
• The determination of ionized Ca2+ (elevated to 6-9mg/dl) is useful for the
diagnosis of hyperparathyroidism

42. Clinical features of hypercalcemia
• Neurological symptoms such as depression, confusion, inability to
concentrate
• Generalized muscle weakness
• Gastrointestinal problems such as anorexia, abdominal pain, nausea,
vomiting & constipation
• Renal feature such as polyuria & polydipsia
• Cardiac arrhythemias

43. Hypocalcemia
• Decreased serum Ca2+ < 8.8 mg/dl is called as hypocalcemia
• Causes:
• Hypoproteinaemia:
• If albumin concentration in serum falls, total calcium is low because the
bound fraction is decreased
• Hypoparathyroidism:
• The commonest cause is neck surgery, idiopathic or due to magnesium
deficiency

44. • Vitamin D deficiency:
• May be due to malabsorption or an inadequate diet with little exposure
to sunlight
• Leads to bone disorders, osteomalacia & rickets
• Renal disease:
• In kidney diseases, the 1, 25 DHCC (calcitriol) is not synthesized due to
impaired hydroxylation

45. • Pseudohypoparathyroidism:
• PTH is secreted but there is failure of target tissue receptors to respond to
the hormone
• Clinical features of hypocalcemia:
• Enhanced neuromuscular irritability
• Neurologic features such as tingling, tetany, numbness (fingers and toes),
muscle cramps
• Cardiovascular signs such as an abnormal ECG
• Cataracts

46. Rickets
• Rickets is a disorder of defective calcification of bones
• This may be due to a low levels of vitamin D in the body or due to a
dietary deficiency of Ca2+ & P or both
• The concentration of serum Ca2+ & P may be low or normal
• An increase in the activity of alkaline phosphatase is a characteristic
feature of rickets

49. Osteoporosis
• Osteoporosis is characterized by demineraIization of bone resulting in the progressive
loss of bone mass
• After the age of 40-45, Ca2+ absorption is reduced & Ca2+ excretion is increased; there
is a net negative balance for Ca2+
• This is reflected in demineralization
• After the age of 60, osteoporosis is seen
• There is reduced bone strength and an increased risk of fractures
• Decreased absorption of vitamin D and reduced levels of androgens/estrogens in old
age are the causative factors

53. Proteins
Make up about 15% of the cell
Have many functions in the cell
Enzymes
Structural
Transport
Motor
Storage
Signaling
Receptors
Gene regulation
Special functions

54. Shape = Amino Acid
Sequence
Proteins are made of 20 amino acids linked by peptide
bonds
Polypeptide backbone is the repeating sequence of the N-
C-C-N-C-C… in the peptide bond
The side chain or R group is not part of the backbone or
the peptide bond

55. Levels of Organization
Primary structure
Amino acid sequence of the protein
Secondary structure
H bonds in the peptide chain backbone
-helix and -sheets
Tertiary structure
Non-covalent interactions between the R groups within
the protein
Quanternary structure
Interaction between 2 polypeptide chains

56. Protein Structure

57. Useful Proteins
There are thousands and thousands of different
combinations of amino acids that can make up proteins
and that would increase if each one had multiple
shapes
Proteins usually have only one useful conformation
because otherwise it would not be efficient use of the
energy available to the system
Natural selection has eliminated proteins that do not
perform a specific function in the cell

58. Types of Proteins
Globular Proteins – most of what we have dealt with so far
Compact shape like a ball with irregular surfaces
Enzymes are globular
Fibrous Proteins – usually span a long distance in the cell
3-D structure is usually long and rod shaped

59. Important Fibrous Proteins
Intermediate filaments of the cytoskeleton
Structural scaffold inside the cell
Keratin in hair, horns and nails
Extracellular matrix
Bind cells together to make tissues
Secreted from cells and assemble in long fibers
Collagen – fiber with a glycine every third amino acid in the
protein
Elastin – unstructured fibers that gives tissue an elastic
characteristic

60. Collagen and Elastin

61. Proteins at Work
The conformation of a protein gives it a unique function
To work proteins must interact with other molecules, usually 1
or a few molecules from the thousands to 1 protein
Ligand – the molecule that a protein can bind
Binding site – part of the protein that interacts with the ligand
Consists of a cavity formed by a specific arrangement of
amino acids

62. Ligand Binding

63. Formation of Binding Site
The binding site forms when amino acids from within the protein come
together in the folding
The remaining sequences may play a role in regulating the protein’s activity

64. Antibody Family
A family of proteins that can be created to bind to almost any molecule
Antibodies (immunoglobulins) are made in response to a foreign
molecule ie. bacteria, virus, pollen… called the antigen
Bind together tightly and therefore inactivates the antigen or marks it
for destruction

65. Antibodies
Y-shaped molecules with 2 binding sites at the upper ends of the Y
The loops of polypeptides on the end of the binding site are what imparts
the recognition of the antigen
Changes in the sequence of the loops make the antibody recognize
different antigens - specificity

66. Antibodies

67. Enzymes as Catalysts
Enzymes are proteins that bind to their ligand as the 1st step in a process
An enzyme’s ligand is called a substrate
May be 1 or more molecules
Output of the reaction is called the product
Enzymes can repeat these steps many times and rapidly, called catalysts
Many different kinds

68. Enzymes at Work
Lysozyme is an important enzyme that protects us from bacteria by
making holes in the bacterial cell wall and causing it to break
Lysozyme adds H2O to the glycosidic bond in the cell wall
Lysozyme holds the polysaccharide in a position that allows the H2O to
break the bond – this is the transition state – state between substrate
and product
Active site is a special binding site in enzymes where the chemical
reaction takes place

69. Phosphorylation
Some proteins are regulated by the addition of a PO4 group that allows
for the attraction of + charged side chains causing a conformation
change
Reversible protein phosphorylations regulate many eukaryotic cell
functions turning things on and off
Protein kinases add the PO4 and protein phosphatase remove them

70. Phosphorylation/Dephosphorylation
Kinases capable of putting the PO4 on
3 different amino acid residues
Have a –OH group on R group
Serine
Threonine
Tyrosine
Phosphatases that remove the PO4
may be specific for 1 or 2 reactions or
many be non-specific

71. GTP-Binding Proteins (GTPases)
GTP does not release its PO4 group but rather
the guanine part binds tightly to the protein and
the protein is active
Hydrolysis of the GTP to GDP (by the protein
itself) and now the protein is inactive
Also a family of proteins usually involved in cell
signaling switching proteins on and off

78. Biological Importance
• Fat-soluble vitamins
• Essential fatty acids contained in the fat of natural foods
• Stored in adipose tissue,
– thermal insulator in the subcutaneous tissues and around certain organs
• Myelinization : electrical insulators, allowing rapid propagation of
depolarization waves along myelinated nerves.
• Lipoproteins : Combinations of lipid and protein - important cellular
constituents, occurring both in the cell membrane and mitochondria.
• Means of transporting lipids in the blood.
• Obesity, diabetes mellitus, atherosclerosis
• Role of various polyunsaturated fatty acids in nutrition and health.

80. Lipids Bilayer Plasma Membrane

81. Classification
• The lipids are classified as
– Simple lipid
– Complex lipid
– Precursor and derived lipid

82. Simple lipids
• Esters of fatty acids with various alcohols.
– Fats: Esters of fatty acids with glycerol. Oils are fats in the liquid state.
– Waxes: Esters of fatty acids with higher molecular weight
monohydric alcohols.

83. FATTY ACIDS
• Simplest form of lipids
• Carboxylic acids with HC side chain
• Usually contains an even number of carbon atoms (14C- 20C) –
biosynthesis of fatty acid occurs with sequential addition of 2
carbon atom.
• Chain may be saturated (containing no double bonds) or
unsaturated (containing one or more double bonds)
• It occurs mainly in esterified form.
• Fats of animal origin are more simple than that of plant origin.
• Palmitic acid and stearic acid – most common

84. Major Saturated Fatty Acids

85. Major Unsaturated Fatty Acids

86. Unsaturated Fatty Acids
• Fatty acids may be further subdivided as follows
– Monounsaturated (monoethenoid, monoenoic) acids, containing
one double bond.
– Polyunsaturated (polyethenoid, polyenoic) acids, containing two or
more double bonds.
– Eicosanoids: These compounds, derived from eicosa- (20-carbon)
polyenoic fatty acids, comprise
the prostanoids, leukotrienes (LTs) and lipoxins (LXs). Prostanoids include
prostaglandins (PGs), prostacyclins (PGIs), and thromboxanes (TXs).

87. Essential fatty acids
• The fatty acid cant be synthesized by the body and therefore has to
be supplied in the diet.
• Ex: Linoleic Acid, Linolenic Acid
• Archidonic acid becomes essential – precursor linoleic acid is
not provided in the diet
• Functions of EFA
– Membrane structures and functions
– Transport of cholesterol
– Formation of lipoprotein
– Prevention of fatty liver
• Deficiency of EFA : Phrynoderma – toad skin

88. TRIACYLGLYCEROLS
• Also known as triglycerides
• Main storage of fatty acids
• Esters of the trihydric alcohol
glycerol and fatty acids
• Phosphorylated on sn-3 by glycerol
kinase to give glycerol 3-phosphate
and not glycerol 1-phosphate.

89. Complex Lipids

90. Complex lipids
• It contains groups in addition to an alcohol and a fatty acid.
a. Phospholipids: in addition to fatty acids,
phospholipid contains
– an alcohol,
– a phosphoric acid residue.
– May have nitrogen containing bases and other substituent
Ex: glycerophospholipids the alcohol is glycerol and in
sphingophospholipids the alcohol is sphingosine.
b.Glycolipids (glycosphingolipids): Lipids containing a fatty acid,
sphingosine, and carbohydrate.
c.Other complex lipids: Lipids such as sulfolipids and aminolipids. Ex:
Lipoproteins

91. Phospholipids

92. Glycerophospholipids
• also called phosphoglycerides
• membrane lipids in which two fatty acids are attached in ester
linkage to the first and second carbons of glycerol
• a highly polar or charged group is attached through a
phosphodiester linkage to the third carbon

93. Glycerophospholipids
• Glycerol is prochiral
– no asymmetric carbons
– But attachment of phosphate at one end converts it into a chiral compound.
• Various important types of glycerophopholipids
– Phosphatidic acid
– Lecithin
– Cephalin
– Phosphatidylinositol
– Phosphatidylserine
– Plasmalogens
– Cardiolipin

94. Phosphatidylcholines
• Also known as lecithins
• Present in phospholipids of the cell membrane.
• Choline (part of neurotransmittor) – component of lecithin
• Dipalmitoyl lecithin is a very effective surface active agent - major
constituent of the Surfactant
– Absence - premature infants causes respiratory distress syndrome

95. GLYCOLIPIDS
• widely distributed in every tissue of the body,
• particularly in nervous tissue such as brain
• outer leaflet of the plasma membrane, where they contribute
to cell surface carbohydrates.
• Ex: glycosphingolipid :ceramide and one or more sugars.
– Galactosylceramide
– Gangliosides

96. Lipoproteins
• Complexes of lipid with protein
• Transport vehicle for lipids
• Five types
– Chylomicron
– Very low density lipoprotein (VLDL)
– Low density lipoprotein (LDL)
– High Density lipoprotein (HDL)
– Free fatty acid complexes

97. Precursor and derived lipids
• These include fatty acids, glycerol, steroids, other alcohols,
fatty aldehydes, and ketone bodies, hydrocarbons, lipid-
soluble vitamins, and hormones.

98. Cholesterol
• Best known steroid
• Association with
atherosclerosis.
• Precursor of a large number of equally
important steroids
– bile acids,
– adrenocortical hormones,
– sex hormones,
– D vitamins - Ergosterol
– cardiac glycosides

99. FUNCTIONS OF LIPIDS
LIPIDS

100. 1. Energy storage

101. 2. Thermal insulation

102. Mechanical protection

105. Platelet-activating factor
(PAF) is a potent
mediator that
occurs at very low
concentrations in
cells and tissues

108. Sleep Induction

109. : Isoprene unit.

110. Biological functions:
COO-
arachadonic acid

111. Biological Processes Regulated by
Eicosanoids

112. membrane
in cholesterol and
•Lipid rafts
microdomains
sphingolipids.
•important for neuronal cell adhesion, axon guidance
and synaptic transmission.
•crucial for neural development and function.

113. Structural support

114. Function as antibacterial

115. Precursor

116. TRACE
ELEMENTS IN
ORAL HEALTH

117. INTRODUCTION
• The human body contains elements that can be classifiedas
• 1. Abundant elements
• 2. Trace elements
 ABUNDANT ELEMENTS
• are those that are involved in the formation of covalentbonds.
• They are important constituents of tissues and semi-majorelements.
• often exist in the ionic state.
• involved in functions of the living body through maintenance ofosmotic
pressure and membrane potentials.

118.  TRACE ELEMENTS / MICRO-
NUTRIENTS
• Are chemical micronutrients required
in minute quantity but play a vitalrole
in maintaining integrity of various
physiological and metabolic
processes occurring within living
tissues.
• with excess bioavailability having a
toxic effect on the living organism
• There are 19 trace elementsdivided
into three groups (WHO
classification):
1. Essential elements
2. Probably essential elements
3. Potentially toxic elements

120. They are :
1. zinc (Zn)
2. copper (Cu)
3. selenium (Se)
4. chromium (Cr)
5. cobalt (Co)
6. iodine (I)
7. manganese (Mn)
8. molybdenum (Mo).
ESSENTIAL
TRACE ELEMENTS

121. TRACE
ELEMENTS
AND
NUTRITION
The interactions of micro-nutrients are difficult to study,
since; they occur together in various forms and amounts;
their absorption from the intestinal tract may be exclusively
dependent on their relative concentrations; they can be
synergetic or antagonistic; the amount could depend on the
other essential trace elements in the diet.
Our diet today, comprises of refined food. This is a cause of
concern to a modern man as he may not be receiving
sufficient amount of trace elements in his food sources,
and dietary supplements may be of usage in combating
this shortage.

124. DIETARY
SOURCES AND
FUNCTION

126. • TRACE ELEMENTS:
• they account for only 0.02% of the total body weight.
• As each trace element is related to many enzymes ,deficiency of one trace
element is not associated with any specific clinical presentation, but rather
presents as a combination .
 TRACE ELEMENTS IN ENAMEL
• Because enamel crystals are so small, they have a very large surface area,
allowing great opportunity for the adsorption of foreignions.
• It is likely that all the previously mentioned ions are to some extentalso
• 1. adsorbed at the surface
• 2. or bound water layer, the ‘hydration shell’, including (HPO4)-2 and (Ca)2+
ions.
• These ions are readily exchangeable, unlike ions in thelattice.
• Also adsorbed on the crystal surface are enamel trace elements such as
potassium, zinc, lead and copper.

127. THE EPIDEMIOLOGY OF
DENTAL CARIES IN
RELATION TO
ENVIRONMENTAL TRACE
ELEMENTS
• Incorporation of trace elements into the appetite microcrystals may alter their physical
properties, especially solubility and hence their susceptibility to degradation

128. They are an important part of certain biological
and chemical reactions .
They work in harmony with proteins and often
with certain other co-enzymes.
They attract substrate molecules and enable their
conversion to any specific end product.

129. HEMOSTAT OF
TRACE
ELEMENTS
Homeostatic
regulation is a
process involving
absorption,
storage, and
excretion.
The relative
importance of
these three
processes is
significantly
different among
each of these
trace elements.
Excretions
occurring
through sweat,
urine, bile, and
breathe is a
major
mechanism for
controlling the
quantity of these
elements in any
organisms .
To prevent
adverse
reactions, some
of these
elements are
stored in inactive
forms when
available in
excess
quantities.

130. FACTORS
AFFECTING
TRACE
ELEMENTS
REQUIREMENT
• Though trace elements play a vital role in a variety of processes
needed for life, the occurrence of their deficiencies of any of the
trace elements is relatively uncommon due to the strong
homeostatic mechanisms. However, there are situations that may
make a trace element nutritionally valuable.

131. FUNCTIONS OF
TRACE
ELEMENTS
1. CHROMIUM
• Chromium is an important mineral for obese people, and it is one of
the key minerals in controlling blood sugar and lipid levels.
• As the main ingredient of glucose tolerance factor (GFT), chromium
helps insulin in reducing the blood glucose, by stimulating glucose
uptake from the muscles and other tissues.
• When the chromium levels are less, the circulating level of (GFT) is
less, and as a result, insulin is less effective in reducing blood sugar.
• Hence, blood sugar remains high, stimulating further insulin release,
which is again blocked from being effective.

132. 2. COPPER third most abundant
mineral in the body,.
involved in the release
process of energy inside the
cell and contributes in the
functioning of many
antioxidants.
Controls the formation and
regulation of hormones like
melatonin, via a wide range
of neurotransmitters and
other neuroactive
compounds including the
catecholamine’s.
Helps in collagen
production, formation of red
blood cells and the oxidation
of fats.
Needed for the proper
functioning of vitamin C and
iron absorption.
Required for the production
of the thyroid hormone
thyroxin .
act as both an antioxidant
and a pro-oxidant.
As an antioxidant, Cu
scavenges or neutralizes free
radicals and may reduce
some of the damage they
cause.
As prooxidant :Cu promotes
free radical damage to the
tissues.

133. ROLE IN ORAL
HEALTH AND
DISEASES
osteoporosis and occipital horn formation due to
functional impairment of copper-requiring enzymes
such as ascorbate oxidase and lysyl oxidase
BONE ABNORMALITIES AND PAIN: include a loss of
trabecular formation with thinning of the cortex.
Deficiency of Cu in diet for a prolonged period leads to
anemia and defective keratinization in the oral cavity.
(The anemic effect -decreased ferroxidase activity of
ceruloplasmin and reduced iron oxidation).

134. 3. ZINC
• Is a mineral with a wide application in human health.
• It is needed for a healthy immune system.
• Also needed for cell division, hair, tissue, nails, skin, and muscle growth, synthesis of protein and collagen- which are
needed for wound healing
4. SELENIUM
• are toxic in excess amounts, but trace amounts of selenium are needed for cellular functioning in many organisms.
• biological role of selenium : Act as an ingredient of the antioxidant enzymes glutathione peroxides and
thioredoxin reductase.

135. 5. MOLYBDENUM:
important role of
molybdenum is sharing a
common cofactor
,molybdoprotein, at the
active site in certain
enzymes.
Molybdoprotein is bound on
molybdenum atom through
adjacent sulphur atoms.
In humans, a process of
purine catabolism is
catalysed by a
molybdenum containing
enzyme.
Molybdenum
concentration also
affects protein synthesis,
the metabolism process,
and growth of the body.
6. IODINE:
plays a role in thyroid
hormones regarding the
growth and development of
humans.
The effects of
iodine-deficiency on growth
and development are
denoted by
iodine-deficiency disorders
that are seen at all stages
of development.

136. • Fluorine is only a minute part of the weight of man and enters
the body by both drinking water and foods.
• Body fluoride status depends on multiple factors.
• A low level of fluorine in drinking water is connected to tooth
decay.
• The dental tissue usually shows signs of toxicity, and mottling of
tooth enamel is a well-known feature of excess fluoride
ingestion.
• Long-term exposure to high levels of fluoride leads to dental
decay.
• Further, in the body ionic fluoride rarely exists in blood, most
ingested fluoride is trapped in the bone tissue.
7.FLUORIDE

137. Fluoride
• Very important in preventing dental caries
• Promotes remineralization of decalcified enamel
•Available as tooth paste, solutions and gels Excess cause
flurosis
•Rx- tooth bleeching, microabrasion,
replacement
137

138. MECHANISMS OF ANTICARIES ACTION OF
FLUORIDE
1. INCREASED ENAMEL RESISTANCE
2. INCREASED REMINERALISATION
3. POST ERUPTIVE MATURATION-1960
4. INTERFERENCE WITH ORAL BACTERIA
5. MODIFICATION IN TOOTH MORPHOLOGY

139. • The hydroxyapatite of tooth enamel -composed of phosphate ions (PO43–) and calcium
ions (Ca2+).
• Normal conditions - there is a stable equilibrium between the Ca and phosphate ions in
saliva and the crystalline hydroxyapatite that comprises 96% of tooth enamel.
• pH drops below a critical level (5.5 for enamel, and 6.2 for dentin)- causesthe
dissolution of hydroxyapatite -DEMINERALIZATION.
• When the natural buffer capacity of saliva elevates pH, minerals are reincorporatedinto
the tooth - REMINERALIZATION.

140. • 1. Increase in the enamel’s resistance to acid solubility
• Fluoride reduces solubility of dental enamel by both systemic and topical action.
• Fluoride ingested prior to tooth eruption - development of florapatite at the enamel surfaces –
which are resistant to demineralizing acids.
• Caries – series of demineralization/remineralization cycles where, over time, demineralization
conditions prevail.
• It can be affected in several ways.
• most effective method is by promoting remineralization and slowing down demineralization. This
can be accomplished with fluoride therapy.

141. • 2. Remineralization −
 Greater concentration of fluoride released from
the dissolved enamel or already present on the
plaque, the more will remineralization be favored
and carious process be slowed.
 Use of topical fluoride raises the fluoride level of
tooth surface and underlying tissues to a level
expected to protect against caries
• .

142. • 3. Antibacterial effects of fluoride
 Inhibition of enzymes essential to cell metabolism and growth.
 Lower the surface energy of the tooth.
Can strip off bacteria from hydroxyapatite.
Fluoride can bind more effectively to positively charged areas on the apatite crystalthan
can the bacteria
• 4. Increased rate of post-eruptive maturation:
• At the time of eruption enamel is not completely calcified and undergoes post eruptive
maturation ( 2 years) –enamel calcification continues.

143. DENTAL BENEFITS
• Fluorosis of the deciduous teeth is rarely seen and is not a problem.
• First 2 to 3 years of life are the most critical period for the development ofmottled
enamel on the permanent anterior teeth and for this reasononly.
• – 0.25 mg/day is prescribed from birth until 2 years of age.
• – 0.5 mg/day from 2 to 3 years of age.
• – 1.0 mg/day from 3 until 13 years of age.
• Use of fluoridated water or fluoride supplements as early as 1 year of ageenhance
the formation of the relatively caries – resistant Fluor apatite in the enamel surface

144. • Supplemental fluoride dosage schedule in mg/day according to fluoride concentrationof
drinking water.

145. 8.LEAD AND MERCURY
• Of the many dietary interactions influencing the uptake of lead
or its retention with calcium are important.
• Defects in hemoglobin synthesis and lessened erythrocyte life
span provide biochemical indication of lead exposure in the
absence of clinically detectable signs.

146. TRACE ELEMENTS AND CARCINOGENESIS
macro-nutrients and
micro-nutrients
promote the process of
carcinogenesis such as,
iron, zinc ,copper,
cadmium, berilium,
boron etc.
These metals act in
various ways in
synchronization
with each other
to bring out regulatory
mechanisms in the
human body.
Dysregulation of this
equilibrium leads to
uncontrolled adverse
reactions in the body

147. TRACE ELEMENTS IN ORAL LESIONS
1. TRACE METALS AND ORAL LICHEN PLANUS AND ORAL
LICHENOID REACTIONS:
• Lichen planus, contact allergy and hypersensitivity OLR’s can be
linked to its exposure with metals that are released from metal
alloys commonly used in dentistry.
• There is a hypothesis on a potential link of (OLR’s) with
exposure to Cr, Co, Ni and amalgam alloys as released into the
oral cavity - the most common metal is nickel.
• These trace metals when come into contact with oral mucosa
induce sensitivity reactions in response to the immune-mediated
damage of the basal epithelial keratinocytes.
• Some studies state that OLR due to amalgamation may have a
risk of malignant transformation

148. 2: Trace elements and oral sub mucous fibrosis:
• Is a well-recognized potentially malignant condition of
the oral cavity, leading to oral cancer.
• In developing countries, controlling the devastating,
widespread effects of oral cancer needs interventions
at-risk persons before the disease becomes invasive,
advanced or metastatic.
• So early detection of these pre-malignancies and
preventing them from malignant transformation seem
to be the best available tool in the fight against oral
carcinoma.

149. 3: Trace elements and oral pre cancer and cancer:
• India has highest incidences of OC in the world.
• Development of cancer is a multistep process ,seen arising from a pre-existing potentially
malignant lesion.
• Leukoplakia -most common precancer (85%).
• Alcohol, viruses, genetic mutations, candida infections, and chronic irritation have modifying
effects in the etiology of oral cancer.

150. Trace elements are considered as versatile
anti-cancer agents that help regulate various
biological mechanisms.
Many researchers observed a potential link
between the trace elements and cancer
mortality.
Reduction in the contents of Cu and Zn were
seen in the blood of patients with HN cancer.
The ratio of Cu to Zn is a reliable biomarker in
the development and progression toward
carcinogenesis.
Trace elements such as Cu and Zn have a role
in anticarcinogenic defense mechanism of the
human body

151. Cu is involved in
cell metabolic
activity, as a part
of various
enzymes, which
are chiefly
concerned with
oxidation
reactions.
In one recent
study, it was seen
that the levels of
serum Cu were
raised in OSMF
patients and
gradually
increased as the
clinical staging
OSMF progressed.
Some studies have
shown lower Zn
levels in the
serum of patients
with potentially
premalignant
disorders like in
oral leukoplakia.
This might be due
to consumption of
Zn in counter
reacting to
oxidants
generated from
tobacco or high
copper of areca
quid metabolism.

152. There is reduced
Fe levels in
OSMF patients
due to utility of
iron in collagen
synthesis.
Decreased Fe
content leads to
decreased
epithelial
vascularity
leading to an
increased
penetration of
arecoline, which
leading to
fibrosis.
Insufficient
nutrition due to
burning
sensation and
erosions in
OSMF patients
and raised
tumor burden in
OSCC patients
are considered
to be key factors
for Fe depletion.
Future studies
investigating
the levels of Cu
and Zn in
precancerous
and cancerous
tissue and
correlating them
with serum
changes would
be useful in
establishing the
role of these
micro-nutrients
in oral
carcinogenesis.
However, it can
be stated that
Cu and Zn could
be effectively
used as
biological
markers in the
process of oral
carcinogenesis.

153. Trace elements have been extensively studied in recent
years to assess if they have any modulating effects in the
predisposition of oral malignant conditions.
Relatively less scientific literature has been documented
in the area of oral premalignant conditions.
Zinc levels in the tissue and serum of pre malignancies
may be used in understanding the pathogenesis, and in
establishing treatment.

154. 01
Cariostatic
elements:
F, P
02
Mildly
cariostatic:
Mo, V, Cu,
Sr, B, Li,
Au
03
Doubtful:
Be, Co,
Mn, Zn,
Br, I
04
Caries
inert: Ba,
Al, Ni, Fe,
Pd, Ti
05
Caries
promoting:
Se, Mg, Cd,
Pt, Pb, Si

155. CONCLUSION
Though trace
elements are
required in
minimal
quantities their
presence in the
optimal amount is
essential for the
normal
physiological
functioning of the
body.
They are one of
the corner stone’s
in maintenance of
biodynamic of the
body.
Both, excess and
the deficiency
states lead to
initiation,
promotion, and
progression to
various disease
processes.
Thus, a
comprehensive
understanding of
these trace
elements is
essential and
significant for
disease control
and maintaining
optimal health.

156. REFERENCES
• Darby, M.L., 2013. Mosby's Comprehensive Review of Dental Hygiene-E-
Book. Elsevier Health Sciences.
• Marya, C.M., 2011. A textbook of public health dentistry. JP Medical Ltd.
• Kulkarni N, Kalele K, Kulkarni M, Kathariya R. Trace elements in oral
health and disease: an updated review. Journal of Dental Research and
Review. 2014 May 1;1(2):100.
• Varghese I, Sugathan CK, Balasubramanian G, Vijayakumar T. Serum
copper and zinc levels in premalignant and malignant lesions of the oral
cavity. Oncology. 1987;44(4):224-7.