VITAMINS

Prof Dr Ashok Joshi

 Introduction
• Vitamins were discovered at the
beginning of the twentieth century.
• Definitnioni: An essential, noncaloric,
organic nutrient needed in tiny amounts
in the diet.
 Introduction
• Doctors like to prescribe vitamins and
millions of people take them but it requires a
good deal of biochemical sophistication to
understand why they are needed and how
the body uses them.

• The only disease a vitamin can cure is the

one caused by a defcnieicy of that vitamin.
Classnifcatnioni:
 The Retinoids
• 3 forms of vitamin A
important for health
– Retinal
– Retinoic acid
– Retinol (key player; can
be converted to other
forms)
• β-carotene (a
carotenoid or pigment)
in yellow/orange foods
is a potent provitamin
A
Absorption
 Vitamin A
• Dnietary Sonurces:
Animal Sources: Liver, Kidney, Egg yolk, milk
and milk products, fsh liver oils
Plant Sources; Yellow and dark green
vegetables ; mango, carrots, spinach,
papaya.

Dnietary Requniremeits:
Adults: 5000IU(Men), 4000IU(Women)
Children: 1500 – 5000 IU
Pregnancy: 6000 IU
 Vitamin A defciency
• Defciency symptoms are not immediate since
hepatic stores can meet the body requirement for
sometime.
• Disease are related to skin,eye & growth.
• Nnight blniidiess(Nyctalonpnia): difculty to see in
dim light.
• Xeronpthalmnia: Dryness in cornea & conjuctiva
keratinization of epithelial cells
in certain area of conjuctiva white triangular
plaques known as Bitot’s spot are seen.
If xeropthalmia persist for long ----- corneal ulceration
and degeneration occur--------destruction of
cornea(keratomalacia) --- cause total blindness.
 Eyesight

• A more serious defciency of vitamin A

occurs when the protein keratnii
accumulates and clouds the eye’s outer
vitamin A-dependent part, the cornea.
• Keratniinizatnioni of the cornea can lead to
xeronsnis (drying) and then progress to
thickening and permanent blindness,
xeronphthalmnia.
• 500,000 of the world’s vitamin A-
deprived children become blind each
year due to xeronphthalmnia.
 Vitamin A defciency
• Growth:
growth retardation--- skeletal growth
• Reproduction:
Degeneration of epithelial germinal cells----- resulting in
sterility, termination of pregnancy.
• Skin and epithelial cells:
Skin becomes rough and dry. Pharyoderma.
Keratinization of epithelial cells of GIT, UT, RT
 Skin And Body Linings

• The skin in vitamin A defciency

 Hypervitaminosis A
• Excess consumption leads to toxicity
• Hypervitaminosis A occur after the liver
storage of retinol and its esters exceeds
10,000 IU
• Acute toxicity: abdominal pain,nausea,
vomitting, severe headaches, dizziness,
slugisness
• Chronic toxicity: bone and joint pain,hair
loss,dryness,fssure of lips,
hepatomegaly,weight loss
 Vitamin E
 Naturally occurring antioxidant.
 Also termed as tocopherol
 Isoprenoid-substituted 6-hydroxychromanes
 Tonconpheronls are dernivatnives onf 6-
hydronxy chronmaie rniig (tonconl) rniig
wnith nisonpreionnid snide chanii.
 Vitamin E
 Dietary source
Vegetables oils are rich sources
corn oil, sunflower oil, wheat germ oil
cabbages, peanuts, apple seeds lettuce
meat, milk, butter & egg
 Recommended dietary allowances
Children:- 10-15 IU/ day
Adults:- 20-25 IU/ day
• free radnicals
• an uncharged molecule (typically
highly reactive and short-lived)
having an unpaired valency electron.
 The Extraordinary Bodyguard

• Vitamin E is an antioxidant.
• Oxidative damage occurs when highly
unstable molecules known as free
radnicals, formed normally during cell
metabolism, run amok and disrupt
cellular structures.
• They steal electrons from DNA,
proteins and membrane etc.
The Extraordinary Bodyguard
 Vitamin E - Functions

• Antioxidant
– Free radical scavenger
• Protects cell membranes
• Protects LDL from oxidation
• Protection of double bonds in
polyunsaturated fatty acids
• Prevention of rancidity
• Works in conjunction with
selenium
– Protects lungs from
pollutants
– Protects DNA
– Protects heart
– Others?
 Vitamin E
 Function of vitamin E
 Antioxidant property:
• Removal of free radicals
prevent non enzymatic oxidations(peroxidation) of various
cell components
e.g PUFA( polyunsaturated fatty acids) by O2and free radicals
superoxide O2- and H2O2
• Membrane structure & integrity of cell.
• Protect RBC from hemolysis.
 Vnitamnii K

• Polyisoprenoid substitued napthoquinones

• Required for the production of blood clotting
factors.
• Mainly found in plants and is synthesized by
bacteria
• Vitamin K exists in diferent forms -
 Forms of Vitamin K

• K1, phylloquinone
– Chloroplasts in plants
• K2, menaquinone
– Bacterial synthesis
• K3, menadione
– Synthetic, water soluble
form
– Complexed to improve
stability
 Vitamin K
Types of vitamins
• Vitamin K1(Phylloquinone) :isolated from plant
leaves
• Vitamin K2(Menaquinone) : isolated from putrid
fish meal
• Vitamin K3(Menadione) : synthetic analogue and is
water soluble
 Vitamin K
• Dnietary sonurce:
Vitamin K1 is present chiefy in green leafy
vegetables ; alpha alpha leaves,caulifower,
cabbages, soyabeans, tomatoes.
Vitamin K2 are synthesized by the
bacteria( intestinal bacteria of gut),egg
yolk,meat, liver, cheese & dairy products
• R D A:
70-140 g/day.
 Vitamin K
Functions of vitamin K
• Blood coagulation :
Promotion of blood coagulation by post transcriptional
modifications of blood clotting factors II, VII, IX & X.
• BCF synthesized in inactive form in liver.
Vit K – coenzyme for carboxylation of glutamic acid by
carboxylase.
Precursor of clotting carboxylase Active clotting factors(II,
factors (II, VII, IX, X) vit K VII, IX, X)
(-)
Dicumarol(warfarin)

• Calcium binding proteins of Bones:

Required for carboxylation of glutamic acid residue of
osteocalcin.
 Vitamin K
Defciency of vitamin K
• Defciency of vitamin K is very rare since most
of the common food contain the vitamin.
• In addition the normal fora of intestine also
synthesize vitamin K.
• However defciency may occur due to:
• Prolonged use of antibiotics and sulfa drugs
• Malabsorption and biliary tract obstruction.
Water sonluble Vnitamniis
 Vitamin C

• More than 200 years

ago, any man who joined
the crew of a seagoing
ship knew he might
contract scurvy, which
would end up killing as
many as 2/3 of the crew.

Long voyages without fresh fruits and

veggies spelled death by scurvy for
the crew
 Vitamin C
• Water soluble vitamin
• Also termed as “Ascorbic acid”
• Majority of animals can synthesize ascorbic acid
from glucose via uronic acid pathway.
• Humans and other primates cannot synthesize due to
lack of enzyme L-gulonolactone oxidase.
 Vitamin C
• Dietary Sources:
• Chiefly vegetable sources:
• Citrus foods, Indian goose berry(amla), cabbage,
spinach, tomatoes
• Considerable amount of vitamin C activity is lost
during cooking, processing and storage because of its
water solubility and irreversible degradation to inactive
compound.
RDA:
Adult – 60-70 mg/day
80-90 mg/day – Women during pregnancy and lactation.
 Vitamin C
• Ascorbic acid (reduced form),
dehydroascorbic acid (oxidized form)
• Synthesized by most animals (not by
human)
 Functions of Vitamin C
• Reducing agent (antioxidant)
• Iron absorption
• Synthesis of carnitine, tryptophan to
serotonin, thyroxine, cortiscosteroids,
aldosterone, cholesterol to bile acids
• Immune functions
• Cancer prevention?
• Conllagei syithesnis
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Collagen Synthesis (Fig. 10-12)

 Vitamin C
• Collagen formation: Act as coenzyme in hydroxylation of
proline and lysine.
Hydroxyproline and hydroxylysine are chief constituent of
collagen fiber
• Vitamin C is required for the functional Activity of
fibroblast/Osteoblast
• Iron metabolism :
Vitamin C helps in iron absorption by converting ferric ion into
ferrous form
Helps in the formation of ferritin and also help in the mobilization
of iron from ferritin.
conversion of methemoglobin to hemoglobin
Degradation of hemoglobin to bile pigments require ascorbic acid.
 Vitamin C
• Immunological functions: it enhances the formation of
immunoglobulins also increases the phagocytic action of
leucocytes.
• Essential for tryptophan, tyrosine, folic acid metabolism.
• Hydroxylation of tryptophan to form serotonin
• Formation of epinephrine from tyrosine
• Active form of folic acid is tetrahydrofolate(TH4) – vit C is
required
• TH4 + Vit C – maturation of erythrocytes.
• Bile acid formation the first reaction 7 apha hydroxylase step
needs vit C
 Vitamin C
• Deficiency
• Scurvy characterized by spongy and sore gums, loose
teeth, swollen joints,fragile blood vessels,decreased
immunocompetence,wound healing is delayed,
haemorrhages occur, anemia may be seen
• Due to deficient formation of collagen.
Defciency Symptoms
 Thiamine (Vitamin B1)
• Also termed as antiberi- beri or antineuritic vitamin
• Active form of thiamine is Thiamine pyrophosphate
(thiamin diphosphate)

Chemically it is substituted pyrimidine linked by

methylene bridge with substituted thiazole

• C/F thymine
• Pyrnimnidniie & thniazonle rniig lniiked
wnith methyleie brnidge
 The B Vitamins in UNISON

• B vitamins function as
part of coneizymes
– coenzymes help enzymes
do their jobs
• Coenzyme in enzymatic reactions in which
activated aldehyde unit is transferred

• Oxidative decarboxylation of alpha keto acids

e.g. pyruvate and α-ketoglutarate to acetyl Co
A and succinlyl Co A
• Transketolase in the pentose phosphate
pathway
 Thiamine (Vitamin B1)
 Dietary Sources:
Plants: Cereals,Pulses, Oil seeds, Nuts and yeasts,
Thiamine is present in outer layer (bran) of cereals.
Polishing removes 80% thiamine in cereals.
Animals: Pork, liver and heart, milk

 Recommended Dietary Allowances:

Adults: 1-1.5mg/day
Children; 0.7-1.2mg/day
 Thiamine (Vitamin B1)
 Biochemical Functions:
• Coenzyme Thiamine pyrophosphate is associated with
energy releasing reaction in the carbohydrate
metabolism.
Pyruvate PDH/TPP Acetyl CoA
α- Ketoglutarate α KDH/TPP Succinyl CoA
• Require for the normal functioning of the nervous
system( nerve impulse transmission)
TPP is required for the synthesis of acetylcholine.
• Reactions involving
TPP
 Thiamine (Vitamin B1)
 Deficiency
• Results a condition beri- beri
• Symptoms:
Cardiovascular manifestation:
Palpitation, dysponea,cardiac hypertrophy which may lead to
congestive heart failure.
Neurological manifestation:
Polyneuritis, mental depression, forget fullness, loss of
memory, confusion and fear, irritability ( may lead to
impairment in nerve impulse transmission)
GI tract manifestation:
Loss of appetite, weakness, constipation, nausea, vomiting
 Thiamine (Vitamin B1)
 Types of beri –beri:
• Wet beri- beri:
Characterized by edema of legs,face,trunk
• Dry beri- beri:
Edema not commonly seen.
• Infantile beri-beri:
Seen in infants born to mother suffering form thiamine
deficiency;
Symptoms: sleeplessness, restlessness, vomiting,
convulsions
Death may occur due to cardiac failure.
Thiamin Defciency
 Thiamine (Vitamin B1)
• Wernicke’s encephalopathy and Korsakoff psychosis
Seen in chronic alcoholics
Body demands more thiamine
Insufficient intake or absorption impairment
Characterized by:
loss of memory,
rhythmatical to and fro motion of eye balls.

Toxicity :
Non – Toxic
Intravenous injection may lead to anaphylactic shock
 Riboflavin(Vitamin B2)
• Essential component of FAD and FMN, both are
coenzymes involved in many oxidation and reduction
reactions.
• Riboflavin is yellow fluoresent compound
• It is a heat stable but light sensitive compound
 Ribofavin
• Coenzymes:
– Flavin mononucleotide (FMN)
– Flavin adenine dinucleotide (FAD)
• Oxidation-reduction reactions
• Electron transport chain
• Citric Acid Cycle
• Catabolism of fatty acids
 Functions of Ribofavin
• Accepts electrons
• Electron Transport Chain
• FAD FADH2

• Succinate Fumarate
• Citric Acid Cycle

• Participates in beta oxidation

• FMN shuttles hydrogen ions and electrons
to into the electron transport chain
• Metabolism of oxidized glutathione
 Riboflavin(Vitamin B2)
 Heterocyclic isoalloxazine ring attached to sugar
alcohol, ribitol

 Active riboflavin is FMN( Flavin Mononucleotide) or

FAD( Flavin Adenine Dinucleotide)
 FMN and FAD serve as prosthetic groups of
oxidoreductase enzymes
 Apoproteins + FMN / FAD = flavoproteins

 Flavoproteins + metals( molybdenum/ iron) =

metalloflavoprotein
 Dietary Sources:
Milk and milk products: lactoflavin
Egg- ovoflavin
Liver- hepatoflavin
cereals, fruits, germinating seeds
 RDA:
1.2 – 1.7mg/day ( 0.2-0.5mg in pregnancy)
 Riboflavin(Vitamin B2)
 Biochemical functions
• Coenzymes of riboflavin participates in oxidation
reduction reactions in various metabolic pathway for
energy production.
e.g. Succinate Succinate dehydrogenase Fumarate
FAD FADH2

 Deficiency :
Disturbances of eye is one of the initial symptoms. Eyes
lid becomes rough and the eye becomes sensitive to
bright light , the condition known as photophobia.
 Riboflavin(Vitamin B2)

Skin changes are most obvious in the area of mouth

Chelosis- lips become inflammed and cracks at the corner
of the mouth
Tongue becomes sore and swollen( i.e odema of
pharyngeal and oral mucous membrane) – glossitis
 Niacin
• Also known Pellagra Preventing factor
• Nicotinic Acid
• Niacinamide
• Nicotinamide
• Most essential components of NAD and NADP both are
coenzymes involved in many energy releasing reactions
• NAD + and NADP+ are the most active form of Niacin.
 Niacin(vitamin B3)
 Biosynthesis
• Tryptophan is a precursor of Niacin
• 60mg of tryptophan can give rise to 1mg of Niacin
(pyridoxal phosphate is required as a coenzyme)
• Liver converts tryptophan to niacin when needed
 Dietary Sources
• Liver, yeast, cereals , pulses, peanuts, milk, eggs,
vegetables
 RDA
• 15-20mg(adult) 10-15mg(children)
 Niacin(vitamin B3)
 Biochemical Functions
• NAD and NADP acts as Coenzymes catalyze redox
reactions related to energy metabolism
Pyruvate LDH lactate ; Malate MDH oxaloacetate
• Synthesizes fatty acids, cholesterol, steroid hormones, &
DNA

• Lower LDL & increase HDL(treat Hyperlipidemia)

 Niacin
• Nicotinic acid (niacin) & nicotinamide
(niacinamide)
• Coenzyme
– Nicotinamide adenine dinucleotide
(NAD)
– Nicotinamide adenine dinucleotide
phosphate (NADP)
• Oxidation-reduction reaction
• Metabolic reactions
 Niacin(vitamin B3)
 Deficiency
• Deficiency produce a disease known as Pellagra
(Pelle = skin, agra = rough)

• Niacin is present in maize but is a bound unavailable

form, niacytin.
 Niacin(vitamin B3)
• The disease involves skin, GI tract and CNS.
• Symptoms are common referred to as 3Ds
• Dermatitis
• Diarrhea
• Dementia

if not treated it may lead to Death

 Niacin
• Pellagra symptoms: 4 “D’s”
– Diarrhea
– Dermatitis
– Dementia
– Death
 Pyridoxine(vitamin B6)
• Vitamin B6 (pyridoxine) is water-soluble
• Needed for more than 100 enzymes that play roles in
protein metabolism
• Biological active form is pyridoxal phosphate acts as
coenzymes
• Vitamin B6 are pyridine derivative
• It collectively represent pyridoxine, pyridoxal and
pyridoxamine
 Pyridoxine(vitamin B6)
 Biosynthesis
• Can be formed by many microorganisms and plants
• Human cannot synthesize hence provided in diet
 Dietary sources
• Yeast,Rice polishings,Wheat,corn,cabbage,
• germinating seeds
• Egg yolk, fish, meat and liver
 RDA:
• 2mg/day (adults)
• 0.3-0.4 ( infants)
 Pyridoxine(vitamin B6)
 Biochemical Functions
• Pyridoxal phosphate acts as coenzyme ,principally involved
in amino acid metabolism
• E.g transamination
Alanine +ketoglutarate aminotransferase pyruvate+ glutamate

Decarboxylation
Tryptophan PLP 5 hydroxytryptamine ( serotonin—neurotransmitter)

Histidine histamine—vasodilator, lowers blood pressure,

stimultaes gastric secretion, inflammation and allergic
reaction)
Glutamic Acid γamino butyric acid(GABA) + Co2
• Pyridoxal phosphate also functions in
glycogenolysis by taking an integral
part of the mode of action of enzyme
phosphorylase
 Pyridoxine(vitamin B6)
 Deficiency
• Deficiency is rather rare but mostly observed in women
taking oral contraceptives, alcoholics and infants
• Deficiency is associated with neurological symptoms such
as depression, mental confusion, convulsions
• Decrease in hemoglobin level, a hypochromic microcytic
anemia is seen
• The synthesis of Niacin coenzmes are impaired
• The nisoniniaznid-induced peripheral
neuropathy occurring in adult
tuberculous patients results from
a defcnieicy of biologically
active pyrnidonxniie.
• The defcnieicy is caused by the
combination of
isoniniaznid and pyrnidonxniie to form a
hydrazone which is excreted in the urine.
 Biotin
• It acts as a coenzyme for many carboxylation( COOH)
reactions.
 Bniontnii
• Sulphur containing B-complex vitamin
• Heterocyclic sulphur containing mono
carboxylic acid formed by fusion of
imidazole & thiophene rings; valeric
acid side chain
• Biotin is bound covalently to the
enzyme as a pronsthetnic gronup via an
ε-amniion gronup onf a lysniie resnidue
nii the eizyme
• This biotin-lysine conjugated amino
acid is termed as "bnioncytnii" resnidue:
coneizyme (fonrm) onf bniontnii
 Biotin
• Free and bound form
• Bnioncytnii (protein bound form)
• Bniontniinidase in small intestine
• Metabolism of CHO, fat, protein (C
skeleton)
• DNA synthesis
 Biotin
 Dietary Sources
• Cauliflower, legumes, tomatoes, grains, nuts, yeast, bananas
• Liver kidney milk and milk products, egg yolk

 RDA
• 100-300 micro gram/day
 Functions of Biotin
• Assists in the addition of CO2 to
substances
• Carboxylation of acetyl-CoA to form
malonyl-CoA for the elongation of a
fatty acid chain
• Addition of CO2 to pyruvate to yield
oxaloacetate
 Biotin(vitamin B7)
 Biochemical Functions
• Biotin involved in many metabolic reactions and acts as a
coenzymes for the carboxylase enzyme that catalyze the
carboxylation reaction . i.e carrier of CO2 in carboxylation
reaction
Pyruvate Pyruvate carboxylase oxaloacetate

Acetyl CoA Malonyl CoA (first step in FA synthesis)

 Biotin(vitamin B7)
 Deficiency
• Very uncommon
• Seen in: Individuals who eat large quantities of raw egg
whites

• Destruction of intestinal flora due to prolonged use of drugs

 Pantothenic Acid
• Biological active form is coenzyme A
• Pantothenic acid consists of β-alanine and pantoic acid

• Dietary Sources:
• Widely distributed in plants, animal tissues and food materials.
• Liver ,egg yolk, kidneys, yeasts, cereals, and legumes, milk
and milk products.

• RDA:
• Adult - 5-10 mg/day
• Children - 4-5mg/day
Paithontheinic Acnid
• Conisnists onf paitonnic acnid & β-
alainiie, peptnide lniikage
• paitonnic acnid + β-alainiie =
Paithontheinic acnid
• Free acnid nis water sonluble,
thermon labnile .
• Coneizymnic fonrm nis ConA &
ceitral ronle nii all metabonlnism.
Coenzyme-A (CoA-SH)
• CoA has SH group ( sulfhydryl group
) which form thioester linkage with
fatty acid.

• CoA .S H + HO OC 3 HC =

• water + CoA S-OC 3HC ( acetyl

CoA)
 Pantothenic Acid
• Biochemical Functions:
• The biochemical functions of pantothenic acid is exerted
through coenzyme A
• Coenzyme A is the central molecule involved in all the
metabolisms (carbohydrate, lipid and protein) also regarded
as coenzyme of metabolic integration.
 Formation of “active acetate”(Acetyl CoA)
Pyruvate CoA /PDH Acetyl CoA
Acetyl CoA participates in a number of important metabolic
reactions
Oxaloacetate + Acetyl CoA citric acid
Acetyl choline formation
Acetyl CoA + Choline Acetyl choline + CoA
 Pantothenic Acid
Synthesis of cholesterol: Acetyl CoA is the starting materials
for cholesterol biosynthesis via HMG-CoA
Formation of ketone bodies

 Formation of succinyl coA

α-Ketoglutarate Succinyl CoA
Succinyl CoA is involved in many important metabolic reactions
e.g. Heme synthesis
Succinyl CoA + glycine δALA( the first step in the
pathway of heme synthesis)
• Ii sonme onf metabonlnic rxi, gronup traisfer
nis nimponrtait whnich onccurs nii a
coneizyme-A bonuid fonrm
– Acetyl ConA + Chonlniie  Acetylchonlniie + ConA
– Acetyl ConA + onxalonacetate  Cnitrate + ConA

• Paithontheinic acnid nitself nis a conmponieit

onf fatty acnid syithase conmplex aid nis
niivonlved nii the fonrmatnioni onf Fatty acnids
 Pantothenic Acid
• Role in lipid metabolism:
Oxidation of fatty acids (β- oxidation)
Fatty Acid Thiokinase/CoA AcylCoA
Pantothenic acid is a component of fatty acid synthase
complex, thus involved in formation of fatty acids.

Deficiency syndrome:
Rare
But deficiency may lead to burning feet syndrome - pain and
numbness in the toes, sleeplessness, fatigue etc.
 Folic Acid
• It consists of three components pteridine ring,
p- aminobenzoic acid and glutamic acid
• Active form of folic acid is tetrahydrofolate(THF or FH4)

• As polyglutamate, folic acid is stored to some extent in

liver.
• Body can store 10-12 mg of folic acid which lasts for 2-3
months.
• N5-methyltetrahydrofolate- found in circulation.
 Functions of Folate
• DNA synthesis
– Transfer of single carbon units
– Synthesis of adenine and guanine
– Anticancer drug methotrexate
• Homocysteine metabolism
• Neurotransmitter formation
 Folic Acid
• Dietary sources:
Green leafy vegetables, cereals
Liver ,eggs

• RDA:
• 100 µg/day
• Pregnancy- 300 µg/day

• Carrier of activated one-carbon units like

methyl,methylene,methenyl, formyl, forimino.
 Folic Acid
• Biochemical functions:
• Tetrahydrofolate is actively involved in the one carbon
metabolism.
• It serves as an acceptor or donor of one carbon units (formyl,
methyl) that are used in amino acids and nucleotide
metabolism.
• Serine transferase Glycine
FH4 FH4-CH2

• Biosynthesis of purine and pyrimidine nucleotides and

consequently nucleic acids.
• Conversion of uridylate to thymidylate is by methylation
•Methotrexate– an analog of 10-methyl-tetrahydrofolate inhibits
dihydrofolate reductase and has been used as an anti-cancer drug
•DIHYDROFOLATE REDUCTASE of some bacteria and parasites difer from
human enzyme; inhibitors of these enzymes can be used as antibacterial
drugs eg, trimethoprim, and antimalarial drugs, eg pyrimethamine
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Neural Tube Defects

(Fig. 10-8)
•Spina bifda
•Anencephaly
•Importance of folate
before and during
pregnancy
 Folic Acid deficiency
• Deficiency may lead to megaloblastic anemia
• Other symptoms may be : glossitis, cheilosis,
gastrointestinal disturbances
• Similar signs and symptoms of
vitamin B-12 defciency
• Pregnant women
• Alcoholics
– Interferes with the enterohepatic
circulation of bile/folate
 Cobalamin(VitaminB12)
• It is also known as anti pernicious anemia vitamin
• Only synthesized by microorganisms and not by plants and
animals
• It is required for the maturation of erythrocytes

• Dietary Sources:
• Food of animal origin- liver, kidney, pork , chicken, milk
and milk products, curd, egg.
• RDA:
• Adult - 3 µg/day
• Children – 0.5-1.5 µg/day
• Pregnant/Lactating women - 4 µg/day
 Conbalamnii (B12)

• Conrrnii rniig wnith ceitral conbalt

 Vitamin B-12
• Cyanocobalamin. methlcobalamin,
5-deoxyadenosylcobalamin
• Contains cobalt
• Folate metabolism
• Maintenance of the myelin sheaths
• Rearrange 3-carbon chain fatty acids
so can enter the Citric Acid Cycle
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Absorption of Vitamin B-12 (Fig. 10-

10)
 Functions of Vitamin B-12
• Helps convert methylmalonyl CoA to
succinyl CoA (citric acid cycle)
• RBC formation
• Nerve functions
– Maintains myelin sheath
• Megalobalstic anemia
Defciency of Vitamin B-12
• Perinicnionus aiemnia
– Never degeneration, weakness
– Tingling/numbness in the extremities (parasthesia)
– Paralysis and death
– Looks like folate defciency
• Usually due to decreased absorption ability
• Achlonrhydrnia especially in elderly
• Iijectnioni of B-12 needed
• Takes ~20 years on a defcient diet to see
nerve destruction
• B 12 extrinisic factor
• Intrinsic factor (glycoprotein ) produced
by parietal or oxyntic cells of stomach
which also produce HCl
• Absorbed in the ileum
• Antibodies that destroy parietal cells
result in defciency of B12 and also
achlorhydria
• Gastrectomey for early gastric carcinoma
 Cobalamin(VitaminB12)
• Biochemical Functions:
• Synthesis of methionine from homocysteine
Homocysteine cobalamin Methionine
N5 MethylTHF THF
• Isomerization of methylmalonyl CoA to succinyl CoA
• Deficiency:
• leads to pernicious anemia due to DNA synthesis
impairment and absence of cell division
• Vitamin B12 deficiency is also associated with neuronal
degeneration and demyelination of nervous system due to
deficiency of methionine
• There is homocysteinuria
• There is irreversible degeneration of
cord as a result of failure of
methylation of one arginine residue
in the myelin basic protein.
• This is due to methionine defciency
in the CNS
 Who is at Risk For
Defciency?
• Vegans
• Breastfed infants of vegan moms
• Elderly
• Individuals with AIDS or HIV
Vitamin B12
Vitamin D - Sources
• Not found naturally in
many foods
• Synthesized in body
• Plants (ergosterol)
• Fluid milk products are
fortifed with vitamin D
• Oily fsh
• Egg yolk
• Butter
• Liver
• Difcult for vegetarians
 Vitamin D: The Sunshine
Vitamin

• Not always
essential
– Body can make it if
exposed to enough
sunlight
– Made from
cholesterol in the
skin
 Vitamin D

• Vitamin D = calciferol
• Vitamin D2 = ergocalciferol
– Completely synthetic form produced by the
irradiation of the plant steroid ergosterol
– Plant source – cannot be used by birds
• Vitamin D3 = cholecalciferol
– Produced photochemically by the action of
sunlight or ultraviolet light from the
precursor sterol 7-dehydrocholesterol
– Animal source – required by birds
 Formation of Vitamin D
• Skin (UV light)
– 7-dehydro cholesterol  vitamin D3
– Ergosterol  vitamin D2
• Liver
– OH-group added
• 25-hydroxy vitamin D3
• Storage form of vitamin (~3 months storage in liver)
• Kidney
– OH-group added by 1-hydroxylase
• 1,25-dihydroxy vitamin D3
• Active form of vitamin D, a “steroid hormone”
– OH-group added by 24-hydroxylase
• 24,25-dihydroxy vitamin D3
• Inactive form of vitamin D, ready for excretion
 Vitamin D - Functions
• Functions
– Bone development
• Calcium absorption (small intestine)
• Calcium resorption (bone and kidney)
• Maintain blood calcium levels
• Phosphorus absorption (small intestine)
– Hormone
• Regulation of gene expression
• Cell growth
Vitamin D Functions
 Vitamin D Afects
Absorption of Dietary Ca

• 1,25-(OH)2 D
binds to vitamin D
receptor (VDR) in
nucleus
• Increase in
calbindin
(Ca-binding
protein)

Groff & Gropper, 2000

 Vitamin D Afects
Absorption of Dietary
• Phosphorus
1,25-(OH)2 D 3 increases activity of
alkaline phosphatase
– Hydrolyses phosphate ester bonds
• Releases phosphorus
• Increase in phosphate carriers
 Bone Metabolism
• Osteoclasts
– Break down bone
• Calcium resorption
– Derived from stem cells
• Diferentiate after stimulation by vitamin D
• Osteoblasts
– Bone-forming cells
– Secrete collagen, which calcifes
• Bone contains 60–66% Ca by weight
– Hydroxyapatite, Ca10(PO4)6(OH)2
 Vitamin D - Defciency
• Young animals
– Rickets
• Failure of bones to grow properly
• Results in “bowed” legs or knock-knees, outward bowed
chest and knobs on ribs
• Older animals
– Osteomalacia: Adult form of rickets
• Softening of bones, bending of spine, and bowing of legs
– Osteoporosis (porous bones):
• Vitamin D plays a major role along with calcium
• Loss of vitamin D activity with advancing age
• Associated with fractures  very serious for geriatrics
Vitamin D Deficiency - Rickets
 Osteomalacia

Normal pelvis
 Vitamin D Toxicity
• Calcifcation of soft tissue
– Lungs, heart, blood vessels
– Hardening of arteries (calcifcation)
• Hypercalcemia
– Normal is ~ 10 mg/dl
– Excess blood calcium leads to stone formation in kidneys
• Lack of appetite
• Excessive thirst and urination