1. Akash Mahadev Iyer
S₂ M.Sc Biochemistry
University of Kerala
Kariyavattom

2.  Vitamins are organic compounds which are required for the normal
physiological function (i.e., maintenance, growth, development, and/or production.
 They cannot be synthesized in the body, but must be provided in the diet.
 They are required in very small amounts, of the order of mg or μg/day,
 Different chemical compounds that show the same biological activity are collectively
known as vitamers
 There are 13 vitamins required by humans , which can be subdivided into;
I. Fat soluble (vitamins A, D, E and K) and
(The B-Complex vitamins and Vitamin C).

3. Vitamin -A Vitamin-D Vitamin-E Vitamin-K
Vitamin-D₂ Vitamin-D₃ Vitamin-K₁ Vitamin-K₃
B-complex vitamins
Based on Stability
Non B-complex vitamin
Thermo labile Thermostable
Vitamin B₂ Vitamin B₃ Vitamin B₆ Vitamin B₁₂
Folic acidBiotin
Ergocalciferol Cholecalciferol
Thiamine
Niacin
Vitamin B7
Based on solubility in oil Based on solubility in water
Retinol Tocopherol
Phylloquinone Menadione
Vitamin-C
Pantothenic acid
Vitamin B₅
Cyanacobalamine
Vitamin B₉
Based on type of source
Pyridoxine
Vitamin B₁

5. Basic Structural Moiety Of Fat Soluble Vitamins
FAT
SOLUBLE
VITAMINS
BASIC STRUCTURAL MOIETY
Vitamin - A Diterpenoid
Vitamin - D Steroidal moiety
Vitamin - E Chromane ring system with isoprenoid side chain.
Vitamin - K Napthaquinone derivative

6. Vitamin A
 Substituted β-ionone nucleus (4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-buten-2-
one)
 Side chain composed of three isoprenoid units joined head to tail at the 6-
position of the β-ionone nucleus

7. Vitamin A is the generic descriptor for compounds with the qualitative biological
activity of retinol.
Owing to their close structural similarities to retinol, they are called retinoids.
The Vitamin A-active retinoids occur in nature in three forms:
The alcohol … retinol
The aldehyde … retinal (also retinaldehyde)
The acid … retinoic acid

8. Vitamin A
Two forms of vitamin A are available in the human diet:
 Preformed vitamin A: Retinoids ANIMAL
 Provitamin A: Carotenoids PLANT
Most of preformed vitamin A in diet- retinyl esters.
Lumen of SI
RetinolRetinyl ester hydrolase
Retinyl esters
Retinyl esters and carotenoids are
transported to the liver in
chylomicron remnants.
Retinol is released from the liver bound
to an α-globulin, retinol-binding protein.
(RBP); - maintain the vitamin in aqueous
solution, protects it against oxidation and
also delivers the vitamin to target tissues.

9. Provitamin A:
 Some plants contain provitamin A carotenoids, which are converted to
retinoids in your body.
 Carotenoids, including β-carotene, are pigments which give orange
color to carrots, cantaloupe, sweet potatoes. There are carotenoids in,
spinach and broccoli… but they’re green…. What makes them green?

10. Vitamin A: Retinoids (ANIMAL)
 Preformed vitamin A is only found in animal foods:
liver, eggs, fortified milk, cheese

12. RDA
• The daily requirement of vitamin A is expressed as retinol equivalents (RE)
rather than International Units ( lU) .
1 retinol equivalent =1 μg retinol
 =6 μg β-carotene
 =12 μg other carotenoids
 =3.33 lU of vitamin A activity from retinol
 =10 lU of vitamin A activity from β-carotene
 The RDA of vitamin A for adults is around 1000 retinol equivalents (3,500
lU) for man and 800 retinol equivalents (2,500 lU) for woman
One International Unit ( lU) = 0.3 mg of retinol
The requirement increases in growing children, pregnant women and lactating
mothers (additional intake of 350 µg vitamin A per day during lactation)

15.  Vision
 Cell differentiation, growth, reproduction
 Bone development
 Immune system
Functions: Vitamin A

17. Vitamin A
Too little: Avitaminosis A
 Chronic vitamin A deficiency can cause night blindness- reversible -dark adaptation time
is increased
 Prolonged vitamin A deficiency leads to - permanent damage to the
cornea
 Number-one cause of preventable blindness in children, mostly in developing countries
 Vitamin A deficiency also associated with stunting of bones.
CONJUNCTIVAL XEROSIS
Conjunctiva becomes dry and non-wettable
Bitot’s Spot
It is triangular ,pearly-white or yellowish foamy spot on the bulbar conjunctiva on either side of
cornea.
CORNEAL XEROSIS
1. Cornea appears dry,dull and non-wettable and eventually opaque.
2. Severe cases may lead to corneal ulceration.
3. Ulcer heals leaving scar which may affect vision.
1. Liquefication of cornea.
2. Cornea may become soft and burst open
3. If eye collapse- vision is lost.

18. Hypervitaminosis A
 Because vitamin A is fat soluble, the body stores excess amounts, primarily in the
liver, and these levels can accumulate.
 Chronic intakes of excess Vitamin A lead to dizziness, nausea, headaches, skin
irritation, coma, and even death
 Although Hypervitaminosis A can be due to excessive dietary intakes, the condition is
usually a result of consumingeformed Vitamin A from supplements
The symptoms include ;
Dermatitis (drying and redness of skin), enlargement of liver, skeletal decalcification
(pain in joints and bones), tenderness of long bones, loss of weight, irritability, loss of
hair, joint pains etc.
Carotenoids in food are not toxic but can turn your skin colour orange!

19. Side-chain-substituted, open-ring steroid
cis-Triene structure
Open positions on carbon atoms at
positions 1 (ring) and 25 (side chain)
1,25-dihydroxy vitamin
D (calcitriol)
Animal version: vitamin D3
or cholecalciferol
Plant version: vitamin D2
or ergocalciferol

20. Fully active form of
the vitamin
Calcidiol , is the main circulating form of the vitamin
Major route of vitamin D excretion -bile,
Calcitroic acid is the major product of calcitriol metabolism

22. The daily requirement of vitamin D is 400 IU or 10
mg of cholecalciferol.
In countries with good sunlight (like India) the RDA
for vitamin D is 200 lU (or 5 mg cholecalciferol).
RDA

24. Functions of Vitamin D

25.  Active form in the body acts as a hormone
 Vitamin D promotes calcium absorption
in the gut and maintains adequate calcium and
phosphate concentrations to enable normal
mineralization of bone.
 It is also needed for bone growth and bone
remodeling by osteoblasts and osteoclasts.
 Vitamin D has other roles in the body,
including modulation of cell growth,
neuromuscular and immune function, and
reduction of inflammation.
 Adequate intake may prevent type 2 diabetes
and some cancers
Functions

26. Vitamin D deficiency
 Too little: Without sufficient vitamin D, bones can become thin, brittle, or misshapen.
 Rickets: vitamin D deficiency disease in children
 On the rise in United States –decreed milk consumption
 The bones of children with rickets aren’t adequately mineralized with calcium and
phosphorus, causing them to weaken and leading to bowed legs
 Osteomalacia: adult equivalent of rickets

27. Hypervitaminosis
 Intoxication with vitamin D causes weakness, nausea, loss of appetite, headache, abdominal
pains, cramps, and diarrhea.
 Also causes hypercalcemia, with plasma concentrations of calcium between 2.75-4.5 mmol /L
 At plasma concentrations of calcium above 3.75 mmol per L, vascular smooth
muscle may contract abnormally, leading to hypertension and hypertensive
encephalopathy.
 Hypercalciuria may also result in the precipitation of calcium phosphate in the renal tubules
and hence the development of urinary calculi.
 Hypercalcemia can also result in calcinosis – the calcification of soft tissues, including
kidneys, heart, lungs, and blood vessels.

28. Vitamin D deficiency
symptoms
Rickets

29.  Side-chain derivative of a
methylated 6-chromanol nucleus.
 Side chain consists of three
isoprenoid units joined head to tail
 Free hydroxyl or ester linkage on
C-6 of the chromanol nucleus
 Lipid-soluble antioxidant
 Vitamin E -two families of
compounds, the tocopherols and the
tocotrienols .
 Derivatives that exhibit
qualitatively the biological activity of
α-tocopherol.
Vitamin E

30.  Absorbed from the small intestine
 Essential for normal reproduction in many animals, hence known as anti-sterility
vitamin. .
 Vitamin E acts to protect PUFA in membrane lipids from damage by free radicals.
 Free radicals (X•) are produced in cells under normal conditions either by
homolytic cleavage of a covalent bond. Eg; O2
•− and H2O2
 The first line of defence involves metalloenzymes such as selenium-containing
glutathione peroxidase, zinc-containing catalase, and copper, zinc and manganese-
containing .
 The main function of vitamin E is as a chain-breaking, free radical trapping
antioxidant in cell membranes and plasma lipoproteins.

31.  Reactivity of the phenolic hydrogen on its C-6 hydroxyl group and the ability of
the chromanol ring system to stabilize an unpaired electron, capable of
terminating chain reactions among PUFAs in the membranes wherein it resides.
 This action, termed free-radical scavenging, involves the donation of the
phenolic hydrogen to a fatty acyl free radical (or O2•−) to prevent the attack of that
species on other PUFAs.
Free radical scavenging by Vitamin E

32. Selenocysteine-catalytic site of
glutathione peroxidase.
glutathione peroxidase catalyzes the
reduction of the tocopheroxyl radical
back to tocopherol.
Glutathione peroxidase reduces
hydrogen peroxide and so lowers
the amount of peroxide available for
the generation of radicals, whereas
vitamin E is involved in removing the
products of attack by these radicals
on lipids.

33. Other Functions
 Vitamin E preserves and maintains germinal epithelium of gonads for proper reproductive
function-
 lt increases the synthesis of heme by enhancing the activity of enzymes ALA synthase and
ALA dehydratase.
 Vitamin E prevents the oxidation of Vitamin A and carotenes.
 It is required for proper storage of creatine in skeletal muscle.
 Vitamin E protects liver from being damaged by toxic compounds such as CCl4
 It works in association with vitamins A, C and β-carotene, to delay the onset of cataract.
 In plants, tocotrienols are synthesized from HMG CoA -precursor for cholesterol synthesis.
High levels of tocotrienols reduce the activity of HMG CoA reductase- rate-limiting enzyme
in the pathway for synthesis of both cholesterol and tocotrienols,by repressing synthesis of the
enzyme

34. RDA
 Intake of vitamin E is directly related to the consumption of PUFA.
.
 Requirement increases with increased intake of PUFA.
 A daily consumption of about l0 mg (15 lU) of 8 α-tocopherol for
man and 8 mg
(12 lU) for woman is recommended.
1 mg of α-tocopherol = 1.5 lU
Pregnancy – 15 mg
Breastfeeding – 19 mg

36. Vitamin E deficiency
 Severe fat malabsorption, cystic fibrosis, chronic cholestatic hepatobiliary
disease, patients who lack the hepatic tocopherol transfer protein
 Deficient female animals suffer the death and resorption of the fetuses.
 In male animals, deficiency results in testicular atrophy and degeneration of the
germinal epithelium of the seminiferous tubules.
 Both skeletal and cardiac muscle are affected in deficient animals- called
necrotizing myopathy.
 The nervous system is affected, with the development of central nervous system
necrosis and axonal dystrophy. This is exacerbated by feeding diets rich in PUFA
 Increased fragility of erythrocytes

38. Hypervitaminosis E
 Vitamin E is one of the least toxic of the vitamins.
 At very high doses, however, vitamin E can antagonize the functions of other
fat-soluble vitamins.
 Impairs bone mineralization, reduces hepatic storage of vitamin A, and
coagulopathies. – can be corrected with an increased dietary supplemention of the
appropriate vitamin (i.e., vitamins D, A, and K, respectively)
 Negative effects in human subjects consuming up to 1000 IU of vitamin E/day
included headache, fatigue, nausea, double vision, muscular weakness, mild
creatinuria, and gastrointestinal distress.
 Potentially deleterious metabolic effects of high level vitamin E status include
inhibitions of retinyl ester hydrolase and Vitamin K-dependent carboxylations.

39. Vitamin K koagulations-vitamine
 Derivative of 2-methyl-1,4-naphthoquinone
 Ring structure has a hydrophobic constituent at the 3-position and can be
alkylated with an isoprenoid side chain
Vitamers of vitamin K
Three compounds have the biological activity of vitamin K:
 Phylloquinone, the normal dietary source, found in green leafy vegetables;
 Menaquinones, a family of related compounds synthesized by intestinal bacteria,
with differing lengths of side-chain;
 Menadione and menadiol diacetate, synthetic compounds that can be
metabolized to phylloquinone.

40.  Discovery- bleeding disorder (haemorrhagic disease) of cattle fed on silage made
from sweet clover and of chickens fed on a fat-free diet.
 The missing factor in the diet of the chickens was identified as vitamin K, while the
problem in the cattle was that the feed contained dicoumarol, an antagonist of the vitamin.

41. It is the cofactor for the carboxylation of glutamate residues in the post-synthetic modification of
proteins to form the unusual amino acid
The function of γ -carboxyglutamate in these proteins is to chelate calcium and induce a
conformational change that permits binding of the proteins to membrane phospholipids
In addition to blood clotting, γ -carboxyglutamate–containing proteins are found in
Bone (osteocalcin and bone matrix gla protein)
Kidney cortex (nephrocalcin); hydroxyapatite and calcium oxalate containing urinary stones;
Atherosclerotic plaque – this protein is sometimes called atherocalcin,
Gas6
Vitamin K is known to be required for the biosynthesis of sphingolipids by bacteria, by
supporting the activity of serine palmitoyltransferase.
Functions

43. RDA
Vitamin K needs are met with the vitamin K produced by bacteria in our gut.
 Adult females:90 mcg
 Adult males: 120 mcg

44. Sources of Vitamin K

45. The following are some signs of Vitamin-K deficiency
 Easy or excessive bleeding
 Bruising
 Nosebleeds
 Bleeding gums
 Blood in the urine and stool
 Extremely heavy menstrual bleeding
 Liver damage or disease
 Low bone density
 Arterial calcification
 Malabsorption in the digestive tract

46. The most frequent causes of vitamin K deficiency are factors that interfere with the
microfloral production or absorption of the vitamin:
 Lipid malabsorption - biliary stasis, liver disease, cystic fibrosis, celiac disease, and
Ascaris infection can interfere with the enteric absorption of vitamin K.
 Anticoagulant therapy ; certain types of drugs can impair vitamin K function. These include
warfarin and other 4-hydroxycoumarin anticoagulants, and large doses of salicylates.
In each case, high doses of vitamin K are generally effective in normalizing clotting
mechanisms.
 In medical management of thrombotic disorders, over-anticoagulation with warfarin is
common; this is reversed by warfarin dose reduction coupled with treatment with
Phylloquinone.
 Antibiotic therapy; Sulfonamides and broad spectrum antibiotic drugs can virtually sterilize
the lumen of the intestine, thus removing an important source of vitamin K for most animals.

47. Hypervitaminosis K
 Phylloquinone exhibits no adverse effects when administered to animals in
massive doses by any route.
 The menaquinones are similarly thought to have negligible toxicity.
 Menadione, however, can be toxic. At high doses, it can produce hemolytic
anemia, hyperbilirubinemia, and severe jaundice.
Vitamin K shots are routinely administered to newborn babies in U.S. hospitals,
birth centers and by some home birth midwives because out of every 100,000
babies who do not receive vitamin K injections suffer permanent injury or death due
to uncontrolled bleeding in the brain (hemorrhagic disease of the newborn)

48. Vitamin K antagonists

50. References
 Harper’s Illustrated Biochemistry, 26th Edition, McGraw-Hill Companies
 The vitamins: Fundamental aspects in nutrition and health, Gerald F.Combs. 3rd
Edition Elsevier Inc
 Nutritional Biochemistry of the Vitamins, David A. Bender -2nd Edition, Cambridge
University Press
 Introduction to nutrition and metabolism- David A. Bender.–3rd Edition, Taylor &
Francis
 Biochemistry ,U.Satyanarayana, 3rd Edition.
 Slideshare, Google, Pearson Inc.