Vitamins and

Minerals
 Introductions
 Food consists of two important components: Fibbers and nutrients.
 None digestible fibbers inflate the digestive track there by creating an adequate space
where digestion occurs.
 On the other hand nutrients break down to smaller units, absorbed to meet cellular need
for energy, construction, catalysis and regulation.
Nutrients are divided into two classes: macronutrients and micronutrients.
Macronutrients include carbohydrates, lipids, proteins and nucleic-acids. Vitamins and
minerals are called micronutrients.

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 5.1. Vitamins
 Vitamin(vital-amine) is an organic compound that can not be
synthesized by man but is essential for normal health and development
 Polish biochemist Casimir Funk discovered vitamin B1 in 1912 in rice
bran. He proposed the complex be named "Vitamin" (vital amines).
 However, vitamins are heterogeneous group of compounds i.e., they
do not have any chemical or structural similarities.
 By the time it was shown that not all vitamins were amines, the word
was already ubiquitous.
 It is worth remembering the following facts when dealing with
vitamins
1. They are needed in microgram quantities
2. Vitamin deficiency leads to disease.

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Classifications of Vitamins

 Based on solubility Vitamins are

classified as either fat-soluble (lipid
soluble) or water-soluble. Vitamins A,
D, E and K are fat-soluble Vitamin C
and B- complex are water soluble.

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 General features of fat soluble
 Vitamins
Adsorbed with dietary fat in micelles
 Excreted much more slowly
 Their transport in the blood is in the lipoproteins or
attached to specific binding proteins
 Stored in adipose tissue & liver so pose a greater risk
of toxicity when consumed in excess
 Chylomicrons containing fat-soluble vitamins are
transported via the lymph to the bloodstream and
eventually to the liver.
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 Vitamin A

 Vitamin A refers to the derivatives of beta-ionone having biological

activity of all-trans retinol.
 Retinol, retinal and retinoic acid are the most commonly used
vitamin A
 Three other terms used frequently with this vitamin are retinoids,
carotenoids and pro-vitamin A.
 Retinoids comprise retinol, retinaldehyde, and retinoic acid
(preformed vitamin A, found only in foods of animal origin)
 Carotenoids, found in plants, may be divided into two main
categories: carotenes and xanthophylls. The latter include a wide
range of compounds, for example lutein, cryptoxanthin and
zeaxanthin, most of which cannot be converted into vitaminA.
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 Con’t…
 The α, ᵝ -, and γ -carotenes and cryptoxanthin are quantitatively
the most important provitamin A carotenoids.
 Although it would appear that one molecule of , ᵝ -carotene should
yield two of retinol, this is not so in practice; 6 g of ᵝ -carotene is
equivalent to 1 g of preformed retinol.
 The total amount of vitamin A in foods is therefore expressed as
micrograms of retinol equivalents.
 ᵝ -Carotene and other provitamin A carotenoids are cleaved in the
intestinal mucosa by carotene dioxygenase, yielding
retinaldehyde, which is reduced to retinol, esterified and secreted
in chylomicrons together with esters formed from dietary retinol.

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The structure of Vitamin A

The structure of Nutritionally important Retinoids & their

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metabolites 20
β-Carotene: Plant foods contain β-carotene, which can
be oxidatively cleaved in the intestine to yield two
molecules of retinal. In humans, the conversion is
inefficient, and the vitamin A activity of β-carotene is only
about one twelfth that of retinol.

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Vitamin A
Retinoids Carotenoids
 Comprise of  Comprise carotenes
 Retinol  Known as provitamin A
 alpha,beta,gamma carotenes
 Retinaldehyde
 cryptoxanthin
 Retinoic acid  Can be cleaved to yield
 Preformed Vit A found in food in  Retinaldehyde
animal origin
 Retinol
 Retinoic acid
 Carotene dioxygenase
 Cleaved carotenes and other
provitamin A
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 Metabolism of Vitamin A
 Transport to the liver: Retinyl esters present in the
diet are hydrolyzed in the intestinal mucosa, releasing
retinol and free fatty acids.
 Retinol derived from esters and from the cleavage and
reduction of carotenes is re-esterified to long-chain fatty
acids in the intestinal mucosa and secreted as a
component of chylomicrons into the lymphatic system.
 Retinyl esters contained in chylomicron remnants are
taken up by, and stored in, the liver.

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 Metabolism of Vitamin A…
 Release from the liver: When needed, retinol is released from the liver and
transported to extrahepatic tissues by the plasma retinol binding protein (RBP).
 The retinol–RBP complex attaches to specific receptors on the surface of the cells of
peripheral tissues, permitting retinol to enter.
 Many tissues contain a cellular retinol binding protein that carries retinol to sites in the
nucleus where the vitamin acts in a manner analogous to that of steroid hormones.

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Functions of Vitamin A
 Involved in visual cycle: Rhodopsin, the visual
pigment of the rods in the retina, consists of 11 cis-
retinal specifically bound to the protein opsin.
 On account of its established role in the visual
process, it is often called as antixerophthalmic
factor or the “bright eyes” vitamin.
 For growth and development.
 All-transretinoic acid and 9-cis-retinoic acid regulate growth, development, and tissue
differentiation

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Functions of Vitamin A…

 For reproduction: Retinol and retinal

support spermatogenesis in the male and
prevents fetal resorption in the female.
 Maintenance of epithelial cell: Essential for
normal differentiation of epithelial tissues
and mucus secretion.
 Maintains the antioxidant potential of
different tissues
 Anticancer effect
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 Cellular Differentiation

 Been used dermatologically

in treatment of acne, psoriasis
 Components of anti aging
cream

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The role of vitamin A (retinol) in the visual cycle.

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Summary of actions of retinoids

1. Retinols and its precursors are used as dietary supplements.

2. The various forms of retinoic acid are useful in dermatology.
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Sources of Vitamin A

 Vitamin A comes from animal sources such as meat, egg , fish

& diary products
 Beta- carotene, a precursor of Vitamin A comes from green,
leafy vegetables & intensely colored fruits & vegetables.
 Daily requirement: 2-3 mg

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 Deficiency manifestations of
vitamin A
 Xerophthalmia from severe vitamin
deficiency is clinically manifested as
pathological dryness of the
conjunctiva and cornea which may
lead to corneal ulceration and
blindness.
 Night blindness is one of the earliest
signs of vitamin A deficiency. The
visual threshold is increased, making
it difficult to see in dim light.

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Hypervitaminosis A/Toxicity of retinoids

 Results from excessive intake of

Vitamin A (intake of > 7.5 mg/day)
 Manifestations:
a. Skin – dry and pruritic
b. Liver - enlarged and chirrotic
c. Nervous system – ↑ ICP (intracranial pressure)
mimicking symptoms of brain tumor
 Pregnant women particularly should not ingest excessive
quantities of vitamin A because of its potential for causing
congenital malformations in the developing fetus.

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 Vitamins D
 The generic term vitamin D designates a group of
chemically related compounds that possess antirachitic
activity.
 The two most prominent members of this group are
vitamin D2 (ergocalciferol) and vitamin D3
(cholecalciferol).
 Vitamin D2(C28H44O) is derived from a common plant
steroid, ergosterol, and is the form that was employed for
nutritional vitamin D fortification of foods .
 Vitamin D3(C27H44O) is the form of vitamin D obtained
when radiant energy from the sun strikes the skin and
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converts the precursor 7-dehydrocholesterol.

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 Vitamins D…
 Since the body is capable of producing vitamin D3,
vitamin D does not meet the classical definition of a
vitamin.
 A more accurate description of vitamin D is that it is a
prohormone; thus, vitamin D is metabolized to a
biologically active form that functions as a steroid
hormone.
 However, since vitamin D was first recognized as an
essential nutrient, it has historically been classified
among the lipid-soluble vitamins.
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The structure of Vitamin D

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Metabolism of Vitamin D

 The production of 25(OH)D3 is catalyzed by the cytochrome

P450 enzyme, vitamin D3 25-hydroxylase. The 25-
hydroxylase activity is found in both liver microsomes and
mitochondria
 From the liver, 25(OH)D3 is returned to the circulatory system
where it is transported via DBP to the kidney where a second
hydroxyl group can be added at the C-1 position by the
25(OH)D3-1-α-hydroxylase .
 The 1 α -hydroxylase is a mitochondrial cytochrome P450-
dependent mixed function oxidase.

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 VITAMIN D: SYNTHESIS

7-dehydrocholesterol UV
Previt D3
(Provit D3, skin) photolysis
Isomerization
PTH Vit D3
Cyt. P450
(cholecalciferol)
O2, NADPH
ring opening
Cyt. P450
25-hydroxycholecalciferol 25-hydroxylase
(liver) O2, NADPH
1, 25-dihydroxy- 1-hydroxylase
cholecalciferol 25-hydroxycholecalciferol
(Calcitriol) (kidney) (25-hydroxy Vit D3)

BONE / INTESTINE / KIDNEY

Minera- Absorption of Reabsorption of

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lization Ca, Pi Ca, Pi 20
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 Vitamin D Deficiency Syndromes

1. Rickets
There is under mineralization in
children due to less absorption
of Calcium.

There is continued formation

of the collagen matrix of bone,
but incomplete mineralization,
resulting in soft, pliable and
bowing of bones.
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Vitamin D Deficiency Syndromes…

2. Osteomalacia – clinical
manifestation of Vit D
deficiency in adults.
 Results from demineralization
of bone

 Picture shows bowed

legs
of a man with Vitamin
D deficiency which
results in malformation
of the skeleton.

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Vitamin D Toxicity/Hypervitaminosis

 Vitamin D is the most toxic of all vitamins.

 Some infants are sensitive to intakes of vitamin D as low as
50 μg/day, resulting in an elevated plasma concentration of
calcium.
 This
can lead to contraction of blood vessel, high BP and
calcinosis
Manifestations:
a. Loss of appetite, nausea, thirst and
stupor
b. Deposition of Ca+2 in many organs,
particularly the arteries and kidneys due to hypercalcemia.

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 Vitamin E
 Consists of eight naturally
occurring tocopherols, of which α-
tocopherol is the most active.
 No unequivocal unique function for
vitamin E has been defined.

 However, it does act as a lipid-

soluble antioxidant in cell
membranes, where many of its
functions can be provided by
synthetic antioxidants
 Vitamin E is the generic descriptor
for two families of compounds, the
tocopherols and the tocotrienols 10/24/20 36
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 Vitamin E…

 Major lipid soluble

antioxidant in cell membranes
and plasma proteins
 The tocopheroxyl radical is
reduced back to tocopherol by
reaction with Vit C from
plasma
 The resultant monodehydro
ascorbate free radical then
undergoes enzymic or
nonenzymic reaction to yield
ascorbate &dehydroascorbate,
neither of which is a free 10/24/20 37

radical 20
 Vitamin K
 Exists in several forms:
a. Phylloquinone (Vit.k1) – present
in plants
b. Menaquinone (Vit. K2) – present
in intestinal bacterial flora
c. Menadione, menadiol and
menadiol acetate
– a synthetic derivative
 Functions:
a. Formation of mature clotting
factors.
b. Promotes blood clotting on
surface of platelets.

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 Vitamin K is a Coenzyme for
carboxylation of Glutamate

It is a cofactor for carboxylation

of glutamate to form unusual AA
carboxyglutamate which chelates
calcium ion

Initially, vitamin K hydroquinone

is oxidized to the epoxide which
activates a glutamate residue in
the protein substrate to a
carbanion, that reacts with
carbon dioxide to form γ-
carboxyglutamate.

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Role Of Vit. K in Blood Coagulation

 Vitamin K promotes the

carboxylation of the glutamic acid
residues of the precursors of clotting
factors II, VII, IX and X.
 Carboxylation produces mature forms
of the clotting factors and hence
capable of subsequent activation.
 The process is inhibited by dicumarol
and wafarin, a synthetic analog of Vit
K.

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 ROLE OF VITAMIN K IN BLOOD COAGULATION

1. The Gla residues of prothrombin are good chelators of positively

charged Ca+2 ions, because of the two adjacent, negatively charged
carboxylate group.
2. The prothrombin-calcium complex is then able to bind to phospho-
lipids essential for blood clotting on the surface of the platelets.
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Vitamin K Is Also Important in the Synthesis of
Bone Calcium-Binding Proteins

 Two proteins are present in bone that contain γ-

carboxyglutamate,
 Osteocalcin
 Bone matrix Gla protein.
 Osteocalcin also contains hydroxyproline, so its
synthesis is dependent on both vitamins K and C
 Treatment of pregnant women with warfarin can
lead to fetal bone abnormalities (fetal warfarin
syndrome).

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General features of water soluble Vitamins

 Dissolve in water
 Readily excreted by kidney
 Function as a coenzyme & in energy metabolism
 Vitamin C, thiamin and riboflavin are especially susceptible to heat and alkalinity
 Hydrophilic compounds and water leach them from vegetables
 Marginal deficiency more common

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
Ascorbic acid (vitamin C)
The active form of vitamin C is ascorbic acid.
 Vitamin C is designated as ascorbic acid because of its ability to cure and prevent
scurvy
 The main function of ascorbate is as a reducing agent in several different reactions &
O2 radical quencher (antioxidant).
 Vitamin C has a well-documented role as a coenzyme in hydroxylation reactions, for
example, hydroxylation of prolyl and lysyl residues of collagen.

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 Ascorbic acid (vitamin C)…
 Vitamin C is, therefore, required for the maintenance of normal connective tissue, as
well as for wound healing.
 Vitamin C also facilitates the absorption of dietary iron from the intestine.
1. In the synthesis of collagen (found in the skin, skeletal muscles, including granulating
wounds), the peptide-bound proline and lysine in the precursor procollagen are
hydroxylated by prolyl and lysl hydroxylase respectively to form collagen.
2. This hydroxylation reaction requires the presence of ascorbic acid.

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Deficiency of ascorbic acid
A deficiency of ascorbic acid
results in scurvy, a disease
characterized by sore and spongy
gums, loose teeth, fragile blood
vessels, swollen joints, and
anemia .
Many of the deficiency symptoms
can be explained by a deficiency
in the hydroxylation of collagen,
resulting in defective connective
tissue.

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 Thiamine (Vitamin B1)
 Thiamine pyrophosphate (TPP), the active form of the vitamin, is
formed by the transfer of a pyrophosphate group from ATP to
thiamine.
 TPP has a key role in energy-yielding metabolism, especially in
carbohydrate metabolism.
 Thiamine diphosphate is the coenzyme in the 3 multi enzyme
complex that catalyze oxidative decarboxylation
 PDH-complex– carbohydrate metabolism
 KGDH-complex– TCA cycle
 Branched chain keto acid dehaydrogenase – branch chain AA
 It is also a coenzyme for transketolase in PPP (pentose phosphate
pathway).
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The structure of thiamine & its active a. Role of thiamine in PPP
form TPP
b. In PDH-complex reaction & TCA cycle

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 Clinical indications for thiamine
The oxidative decarboxylation of pyruvate and α-ketoglutarate, which plays a key role
in energy metabolism of most cells, is particularly important in tissues of the nervous
system. In thiamine deficiency, the activity of these two dehydrogenase-catalyzed
reactions is decreased, resulting in a decreased production of ATP and, thus, impaired
cellular function.
 Note: Thiamine deficiency is diagnosed by an increase in erythrocyte transketolase
activity observed on addition of thiamine pyrophosphate.

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Thiamine Deficiencies
1. Beriberi is a severe thiamine deficiency syndrome found among
Asians where rice is a staple food, especially if eating well-polished
rice where thiamine has been removed.
 Infantile form manifests as tachycardia, vomiting, convulsions
and death if untreated.
 Adult forms – dry skin, irritability, wasting, disorderly thinking
and progressive paralysis.
2. Wernicke-Korsakoffs syndrome – thiamine deficiency in
association with chronic alcoholism. It is due to dietary insufficiency
or impaired intestinal absorption of the vitamin. Some alcoholics
develop Wernicke Korsakoff syndrome—a thiamine deficiency state
characterized by apathy, loss of memory, ataxia, and a rhythmic to-and-
fro motion of the eyeballs (nystagmus). The neurologic consequences
of Wernicke's syndrome are treatable with thiamine supplementation.
3. Lactic acidosis. Why? 10/24/20
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Riboflavin (Vitamin B2)

1. There are 2 biologically active forms of riboflavin: Flavin Mononucleotide

(FMN) and Flavin Adenine Dinucleotide (FAD).
2. FMN is formed by the transfer of AMP from ATP to riboflavin.
3. FAD is formed by the transfer of AMP from ATP to FMN.
4. FMN and FAD are each capable of reversibly accepting two H+ atoms,
forming FMNH2 and FADH2.
5. FMN and FAD are tightly bound to flavoenzymes that catalyze oxidation-
reduction reactions. 52
Role of FMN and FAD in redox reactions
1. Both FMN and FAD are components of NADH dehydrogenase
and succinate dehydrogenase/glycerol 3-P dehydrogenase
respectively, that are capable of accepting electrons and
donating electrons to the other components of the ETC system.
2. With severe deficiency of riboflavin, there is decreased ATP
synthesis by the mitochondria via oxidative phosphorylation.
ROLE OF FAD IN THE CITRIC ACID CYCLE
2. In the succinate dehydrogenase reaction of the TCA cycle
FAD is an acceptor of two hydrogen from succinate to form
fumarate.
2. FAD is reduced to FADH2 (FADH+ + H+) in the process.

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ROLE OF FAD AND FMN IN NITRIC OXIDE (NO)
SYNTHESIS

NADPH NADP+

Arginine NO + Citrulline
NO synthase
FAD, FMN, Heme
Tetrahydrobiopterin

1. NO is a mediator in a broad array of biologic systems.

2. It is synthesized from arginine, catalyzed by NO synthase which needs

FAD, FMN, heme and tetrahydrobiopterin as coenzymes.
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Riboflavin deficiency
 Riboflavin deficiency is not
associated with a major human
disease although it frequently
accompanies other vitamin
deficiencies.
 Deficiency symptoms include
 Dermatitis
 cheilosis (fissuring at the corners of
the mouth)
 lingual desquamation
 Glossitis

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NIACIN (NICOTINIC ACID, VITAMIN B3)

The term niacin is accepted as a broad descriptor of vitamers that

have the biological activity associated with nicotinamide,
including nicotinamide, nicotinic acid, and a variety of pyridine
nucleotide structures.

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 Functions of niacin
1. The biologically active forms of niacin are Nicotinamide Adenine
Dinucleotide (NAD+) and its phosphorylated derivative,
Nicotinamide Adenine Dinucleotide Phosphate (NADP)+).
2. Nicotinamide, a derivative of nicotinic acid that contains an
amide rather than carboxyl group, also occurs in the diet.
3. NAD+ and NADP+ serve as coenzymes in many oxidation-
reductions reactions.
4. Also a source of ADP-ribose in nuclear proteins. Poly(ADP-
ribose) synthesis makes use of NADP as substrate, rather than as
an electron-transporting intermediate. Poly(ADP-ribose)
formation has been shown to be important in DNA repair and
genomic stability and provides an explanation for sensitivity to
ultraviolet radiation observed in pellagra.
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Role of NAD+ and NADH+ in redox reactions

 In the TCA cycle , NAD+ is a

hydrogen acceptor in the pyruvate
dehydrogenase, isocitrate
dehydroge-nase, α-ketoglutarate
dehydrogenase and malate
dehydrogenase reactions.
 In the process, NAD+ gets
reduced to NADH+ + H+
(NADH2), which then donates its
electrons to the ETC in the
mitochondrion.

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 Niacin deficiency
 Niacin is NOT strictly a vitamin since it can be synthesized in the body from
the essential amino acid tryptophan.

 Deficiency of tryptophan and of niacin causes pellagra - a disease involving

the
 skin, GIT and CNS hence the 3 Ds: dermatitis, diarrhea and dementia.
 Carcinoid syndrome

 In the genetic disorder Hartnup disease, pellagra develops inspite of adequate

intake of both tryptophan and niacin; this is 2 o to a defect of the transport
mechanism for tryptophan → ↓ intestinal absorption and renal reabsorption.

 High doses of niacin inhibits adipose tissue lipolysis, hence may be used in the
treatment of Hyperlipidemia.

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 Pyridoxine (vitamin B6)
 Vitamin B6 is a collective term for
pyridoxine, pyridoxal, and
pyridoxamine, all derivatives of
pyridine.
 Pyridoxine occurs primarily in plants,
whereas pyridoxal and pyridoxamine are
found in foods obtained from animals.

 They differ only in the nature of the

functional group attached to the ring.

 These three compounds can serve as

precursors of the biologically active
coenzyme, pyridoxal phosphate /PLP/

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Pyridoxal phosphate functions as a coenzyme for a large number of
enzymes, particularly those that catalyze reactions involving amino
acids.

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Clinical indications for pyridoxine:
 Isoniazid (isonicotinic acid hydrazide), a drug frequently used to treat tuberculosis, can
induce a vitamin B6 deficiency by forming an inactive derivative with pyridoxal
phosphate.
 Dietary supplementation with B6 is, thus, an adjunct to isoniazid treatment.
Toxicity of pyridoxine
 Pyridoxine is the only water-soluble vitamin with significant toxicity.
 Neurologic symptoms (sensory neuropathy) occur at intakes above 200 mg/day, an
amount more than 100 times the RDA.

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 BIOTIN
 Biotin is a coenzyme in carboxylation reactions, in which it serves as a carrier of
activated carbon dioxide.
 Biotin is covalently bound to the ε-amino groups of lysine residues in biotin-dependent
enzymes.
 Biotin deficiency does not occur naturally because the vitamin is widely distributed in
food.
 Also, a large percentage of the biotin requirement in humans is supplied by intestinal
bacteria.
 However, the addition of raw egg white to the diet as a source of protein induces
symptoms of biotin deficiency, namely, dermatitis, glossitis, loss of appetite, and nausea.
 Raw egg white contains a glyco protein, avidin, which tightly binds biotin and prevents
its absorption from the intestine.

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 Biotin…
 The pyruvate carboxylase reaction is the 1st
and rate-limiting step of gluconeogenesis.
 Biotin (with its attached CO2) is the source
of CO2 in this carboxylation reaction, hence
pyruvate is converted to oxaloacetate.
 Biotin is again a source of CO2 in the
carboxylation of propionyl-CoA to D-
methylmalonyl- CoA which is then
converted to succinyl CoA, a starting
substrate in heme synthesis.

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 Pantothenic acid
Pantothenic acid is a component of
Coenzyme A, which therefore functions in
the transfer of acyl groups because of its thiol
(SH) group.

Examples of compounds with acyl groups are

succinyl CoA, fatty acyl CoA and acetyl CoA.
Pantothenic acid is also a component of the acyl
carrier protein (ACP) domain of fatty acid
synthase
Eggs, liver, and yeast are the most important
sources of pantothenic acid, although the
vitamin is widely distributed.

Coenzyme A takes part in reactions of the

TCA cycle, FA synthesis and oxidation,
acylations and cholesterol synthesis.

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 Folic acid (Pteroyl glutamate)
 Folic acid (or folate), which plays a key role in one-carbon metabolism, is essential for
the biosynthesis of several compounds.
 Tetra hydro folate (reduced folate) receives one-carbon fragments from donors such as
serine, glycine, and histidine and transfers them to intermediates in the synthesis of
amino acids, purines, and thymidine mono phosphate (TMP)—a pyrimidine found in
DNA.
 The active form of folic acid is tetrahydrofolate (THF).
 The major point of entry for 1-carbon fragments into substituted folates is methylene-
THF formed by the reaction of serine, glycine and choline.
 Methylene, methenyl and formyl-THF are interconvertible.
 These different forms of THF are used in the synthesis of amino acids, purines, and
thymine – a pyrimidine found in DNA.

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 Folate and anemia

 Inadequate serum levels of folate can be

caused by increased demand (for example,
pregnancy and lactation), poor absorption
caused by pathology of the small intestine,
alcoholism, or treatment with drugs that are
dihydrofolate reductase inhibitors, for
example, methotrexate
 A folate-free diet can cause a deficiency
within a few weeks.
 A primary result of folic acid deficiency is
megaloblastic anemia , caused by diminished
synthesis of purines and TMP, which leads to
an inability of cells (including red cell
precursors) to make DNA and, therefore,
they cannot divide.
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CLINICAL APPLICATION OF FOLIC ACID INHIBITORS

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 Folate and neural tube defects in the fetus
 Spina bifida and anencephaly, the most common neural tube defects
 Deficiency of this vitamin results to neural tube defects in the fetus.
 Therefore, all women of childbearing age are advised to consume 0.4 mg/day of folic
acid to reduce the risk of having a pregnancy affected by neural tube defects.
 Adequate folate nutrition must occur at the time of conception because critical folate-
dependent development occurs in the first weeks of fetal life — at a time when many
women are not yet aware of their pregnancy.

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 COBALAMIN (VITAMIN B12)
 Vitamin B12 is required in humans for
two essential enzymatic reactions: the
remethylation of homocysteine to
methionine and the isomerization of
methylmalonyl coenzyme A (CoA) that is
produced during the degradation of some
amino acids (isoleucine, valine,
threonine, and methionine), and fatty
acids with odd numbers of carbon

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 With deficiency of Vitamin B12, there is impaired
methionine synthase activity, resulting in the
accumulation of N5-Methyltetrahydrofolate with a
decrease of the other forms of tetrahydrofolate.
 “Folate trap” ensues, resulting to deficiency of the
tetrahydrofolate formsneeded in purine and thymine
synthesis → symptoms of megaloblastic anemia.
 With B12 deficiency → abnormal fatty acids
accumulates and incorporated into cell membranes,
including those of he CNS → neurologic manifestations.
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Cobalamin contains a corrin ring system that differs from the porphyrins in that 2 of
the pyrrole rings are linked directly rather than via a methene bridge.

Cobalt is held in the center of the corrin ring.

5,6-dimethylbenzimidazole and cyanide fill up 2 of the 4 coordination sites of the
corrin ring.

The coenzyme forms of cobalamin are 5’-deoxyadenosylcobalamin (cyanide is

replaced with 5’-deoxy adenosine and methylcobalamin (cyanide is replaced by a
methyl group).

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Pernicious anemia due to vitamin B12 deficiency

 Vit B12 absorption requires an intrinsic

factor (IF) produced by the gastric
parietal cells.
 This cobalamin-intrinsic factor complex
travels through the gut and into the
general circulation.
 In the presence of an autoimmune
destruction of the gastric parietal cells,
the deficiency of intrinsic factor
prevents absorption of Vit. B12, resulting
to a clinical condition called pernicious
anemia.
 Patients later on develop CNS
symptoms.
 Treatment: High-dose Vit B12, oral or
intramuscular.
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End Note

 Most of the water soluble vitamins exert the functions through

their respective coenzymes while only one fat soluble vitamins
(K) has been identified to function as a coenzyme.
 As far as human are concerned, it is believed that the normal
intestinal bacterial synthesis, and absorption of vitamin K and
biotin may be sufficient to meet the body requirements.
 Administration of antibiotics often kills the vitamin
synthesizing bacteria present in the gut, hence additional
consumption of vitamins is recommended.

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5.2. Minerals

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Functions of cations
Cations their functions
Ca2+ Bone formation, Blood Coagulation, Neuromusclar
activity, enzyme activator (eg. Collagenase)
Cu2+ Cofactor (Cytochrome a3)
Co2+ Active center of Vitamin B12
Fe2+ O2 Transport & storage;cofactor of
enzymes:cytochromes
Mg2+ Kinases, etc.
Mn2+ Cofactor of enzymes:Pyruvate carboxylase, xanthine
oxidase
Zn2+ Structural Component of metaloenzymes

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Functions of anions

Anions Their major functions

Cl- Coenzyme of Amylase, synthesis of
HCl
F- Bone formation
I- T3/T4 biosynthesis
HPO4= Bone formation, synthesis of
organic molecules: (DNA, ADP, ATP,
Phospholipids, RNA).
Phosphates serve as pH buffer systems
Selenium Biosynthesis of Glutathione
Peroxidise 10/24/20
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78
Calcium and Phosphate
 Major parts (90%) of them are found in the form of crystal lattice in the bone. Rest is
found in the soft tissues, teeth and ECF.
Calcium Absorption: It is influenced by
 Acidic pH solubilizes Calcium salts, promote absorption.
 High protein diet favors absorption
 Certain plant products, high fiber diet, oxalates interfere with absorption.
 Vitamin D promotes absorption.
 PTH favors absorption while Glucocorticoids decrease intestinal transport.
Functions of calcium
 Calcification of bones and teeth. Bone formation requires Calcium continuously.
 It is important for blood coagulation
 Neuromuscular transmission.
 Muscle contraction
 Acts as secondary messenger in hormone action.
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 A dietary deficiency of calcium can lead to osteoporosis, a disease
in which bones are insufficiently mineralized and consequently
are fragile and easily fractured. Osteoporosis is a particularly
common problem among elderly women.
 Deficiency of phosphorus results in bone loss along with
weakness, anorexia, malaise, and pain.

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 Sodium & Potassium
Functions
 Sodium maintains osmotic pressure of extra cellular fluid and ECF
balance.
 It has a role , along with others, in the neuro muscular excitability
 Sodium is exchanged with Hydrogen in renal tubules to acidify
urine.
 Sodium pump keeps sodium in far higher concentration outside the
cell .This results high polarization, create resting membrane
potential.
 Sodium and Potassium maintain the degree of hydration of plasma
proteins, and there by viscosity of blood.
 Potassium is critically important for the functioning of cardiac
muscle.
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Sodium & Potassium…
Hypernatremia: It occurs nearly always due to water deficiencies rather than Na+
excess. Increased sodium is found in ECF. It may be due to increased sodium in the
body, decreased body water. It is usually seen in patients with dehydration, on steroid
therapy or excess sodium intake.
Hyponatremia: It is common in patients who are in diuretics or excessive sweating,
kidney disease, diarrhea and congestive heart failure
Hyperkalemia is found in patients who are on excess intake orally or given
intravenous drip. Other causes are decreased excretion by the kidney, diseases like
Anuria, tissue damage or Diabetes Mellitus.
Hypokalemia: Low potassium is not due to dietary deficiency but due to conditions
like vomiting, diarrhea. Habitual users of laxatives are prone to the condition.

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Iron balance

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 Haemachromatosis/Bronze DM
 Excessive binding of iron causes denaturation of ferritin molecule. It undergoes
aggregation, to form hemosiderin. Mobilization of iron from hemosiderin is very
slow. Thus there is accumulation of hemosiderin, the condition is called
haemosiderosis.
 Massive deposits of hemosiderin in tissues lead to hemachromatosis.
 If this takes place in liver, it causes cirrhosis. In pancreas, it damages β cells, result in
Bronze diabetes. The skin of the patient has bronze coloration.
 Oxidative damage to cardiac muscle is a biggest concern.

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Function of Zinc

 300 enzymes require zinc

 DNA, RNA polymerases

 numerous hormones require zinc

 insulin
 EGF

 transcription factors (zinc finger proteins)

 membrane stability
 Myelination
 skeletal development