Biochemistry Second Year

1. Vitamins.
Dr. Arafat Ahmad
Asst. Prof. Biochemistry
College of medicine, UOD

2. Definition & Classification.
• Vitamins are organic compound required by
the body in trace amount to perform specific
cellular functions.
• Vitamins classified according to their
solubility and there function in metabolism.
• Vitamins cannot be synthesized by humans
and therefore must be supplied by the diet.

3. FAT SOLUBLE VITAMINS
• GROUP CHARACTERISTICS
• Vitamin A,D, E, K are 4 fat soluble vitamins.
As a group have the following characteristics.
• They are absorbed in the lymphatic system
with fat. Fat soluble vitamin deficiency can
occurs secondary to any condition that
interfere with fat absorption such as mal-
nutrition, pancreatic and biliary disease.

4. Deficiency and Toxicity
• Must be attached to protein carriers in order to
be transported through the blood in the liver
and adipose tissue.
• Fat soluble vitamin deficiency are slow to
develop.
• STORES :
• Do not have to consume every day because
they have body storage reserve. They can be
toxic when consumed in large doses over a
prolonged period of time, particularly Vit. A ,
and Vit D.

5. RDA
• RDA = RECOMMENDED DAILY ALLOWANCE
• It is the amount needed / day to maintain
optimal health and prevent chronic disease

6. Vitamin A
• Active forms :
• Retinol.
• Retinal.
• Retinoic acid.
• Beta carotene ( Plant ).

7. Retinol
• Retinol ( Vitamin A alcohol )
• It is primary alcohol containing beta ionone
ring.
• The side chain has two isoprenoid units,4
double bonds and one hydroxyl group.
• Retinol is present in animal tissue as retinol
esters with long chain fatty acids.

8. Retinal and Retinoic acid
• Retinal ( Vitamin A aldehyde) : This is an
aldehyde form obtain by oxidation of retinol.
• Retinol and Retinal are inter convertible.
• Retinoic acid ( Vitamin A acid ).This is
produced by oxidation of retinal.
• Retinoic acid cannot form retinal or retinol.

9. Beta carotene
• Beta carotene ( pro-vitamin A ) This is found
in plants.
• It is cleaved in the intestine to produced 2
molecule of retinal.
• In human this conversion is inefficient.
• Beta carotene in human possesses only one
sixth vitamin activity compared to retinal.

10. RDA
• Children = 400 – 600 mcg/day.
• Men = 750 – 1000 mcg/day.
• Women = 750 mcg / day.
• Pregnancy = 1000 mcg / day.

11. Absorption ,Transport and
Mobilization
• Dietary retinyl esters are hydrolyzed by
pancreatic or intestinal brush border
hydrolases in the intestine releasing retinol
and free fatty acid.
• Carotene are hydrolyzed by beta carotene 15
-15’-di oxygenase of intestinal cell producing
two molecule of retinal which is reduced to
retinol.

12. In the intestinal mucosal cells
• Retinol is re- esterified to long chain fatty
acids, incorporated to chylomicrons and
transferred to lymph.
• The retinol esters are taken up by liver and
stored.
• Vitamin A is released from the liver as free
retinol.
• Zink plays and important role in retinol
mobilization.

13. • Retinol is transported in the circulation by the
plasma retinol binding protein ( RBP). In
association with pre albumin.
• The Retinol –RBP complex bind to specific
receptor on the cell membrane of peripheral
tissue and inters the cells
• Many cells of target tissue contain a cellular
retinol binding protein that carries retinol to
nucleus and bind to DNA like a steroid hormone.

14. Wald’ visual cycle
(George Wald- Nobel Prize -1968)
• Rhodopsin is a conjugated protein in rods cells
of retina.
• It contains 11-cis retinal and the protein opsin.
• The aldehyde of retinal is linked to epsilon
amino group of lysine of opsin.
• On exposure to light ----isomerization of 11-cis
retinal to All trans retinal occurs.
• This leads to a conformational changes in opsin

15. Retinal epithelium
• This conformational change in opsin is
responsible to generation of nerve impulse.
• The All trans –retinal is immediately
isomerizes to 11-cis retinal by enzyme retinal
isomerase.
• This combine with opsin to regenerate
Rhodopsin and complete the visual cycle.

16. In liver
• Conversion of all trans retinal to 11 cis retinal
is incomplete in retinal epithelium.
• Most of All trans retinal is transported to
liver.
• Converted to all trans retinol by enzyme
alcohol dehydrogenase.
• The All trans retinol is isomerizes to 11 -cis
retinol which is again oxidized to 11 cis-
retinal to participate in visual cycle.

17. Colour Vision
• Retinal –opsin complex---for colour vision
• Porphyropsin----Red.
• Idopsin-----------Green.
• Cynopsin--------Blue.
• These pigments are bleached on exposure to
light, and nerve impulse is generated.

18. Vitamin A-(Functions-cont.)
• Growth
• Reproduction ( Retinol and Retinal )
• Maintenance of epithelial cells
• ( retinoic acid )
• SOURCES :
Liver, kidney, cream, butter, cream, yellow of
eggs, green vegetables, and fruits.

19. Deficiency
• Night blindness : difficult to see in dim light.
• Xeropthalmia : The conjunctiva become
dry, thick and wrinkled. The conjunctiva get
keratinized.
• Bitot’s spots : grayish-white triangular
plaques firmly adherent to conjunctiva.
• Keratomalacia : softening of cornea due to
persistent xeropthalmia.
• Blindness.

20. Clinical use of Vitamin A
• Acne and psoriasis :
• Dermatological problem such as acne and
psoriasis and skin aging are treated with
retinoic acid.
• Prevention of chronic disease :
• Beta carotene decreased the incidence of
heart disease and lung and skin cancer.( anti
oxidant action ).

21. Toxicity of Vitamin A
• Excessive intake of vitamin A produces toxic
syndrome called hyper vitaminosis A.
• Dermatitis-(Dry-red pruritic skin),
Hepatomegaly. Long bone tenderness( pain
on touch)
• Rise in intracranial pressure.
• Congenital malformation of developing
foetus.

22. Vitamin D
• Sources :
Sun light, Fish liver oil, fish , egg yolk.
• Requirement :
1. Children : 10 microgram ( 400 IU ) / Day.
2. Adults : 05 micro gram( 200 IU ) / Day.
3. pregnancy, Lactation : 10mcg (400)/ Day.
4. Above the age of 60 : 15mcg ( 600 ) / Day.

23. Vitamin D
• Pro vitamin :
• 1. Ergosterol ( Plants ).
• 2. 7-dehydrocholesterol( Animal ).
• Endogenous Vitamin Precursor.
• 7- dehydrocholesterol ( skin ).
• Active form : Pro vitamin converted to cholecalciferol
by ultraviolet light.( In skin )
• Vitamin is hydroxylated in liver to –
• 25- hydroxy cholecalciferol.
• Kidney forms-1,25 dihydrocholecalciferol ( Active)

24. Functions
• 1. Regulation of Ca and phosphates levels.
• A) Increase uptake of calcium by the
intestine.
• B) decrease loss of calcium from kidney.
• C) Increase bone resorption.
• DEFICIENCY : Nutritional rickets ( children).
• Osteomalacia : (adult) and renal rickets.
• Most toxic of all vitamins.

25. Body can make Vitamin D
Sun Light-----→Skin ( 7- Dehydrocholesterol)
↓
In skin Cholecalciferol is formed
↓
In liver,25-hydroxycholecalciferol is formed
↓
In kidney,1,25-dihydrocholecalciferol is
formed.

26. Activation of VIT.D.
• Vitamin D is a pro hormone. The cholecalciferol
is first transported to liver, where hydroxylation
at 25th position occurs to form 25-
hydroxycholecalciferol( 25-HCC).
• 25-HCC is major storage form.
• In plasma, 25-HCC is bound to vitamin D binding
protein.
• In kidney- hydroxylation at position 1st occurs
thus 1,25-dihydroxy cholecalciferol( Calcitriol) is
generated----This is the active form of Vit. D.

27. REGULATION OF CALCITRIOLE
• The level of calcitriole is maintained by feed
back control.
• The rate of production is modulated by
serum levels of-------
• calcium,phosphorus,parathyroid hormone
and calcitriole itself.
• The major site of control is on the 1 alpha-
hydroxylase is through PTH.
• Hypercalcemia decreases calcitriole.

28. • Low dietary calcium and hypocalcemia
increases the rate of production of 1,25-
DHCC.
• The stimulatory effect of hypocalcemia on 1-
alpha hydroxylase is through PTH.
• The half life of calcitriole is 6-8 hrs and is
mainly excreted through bile.

29. Deficiency of Vitamin D
• ADULTS-------- Osteomalacia
• Children------- Rickets

30. Causes of Vitamin D Deficiency
• In people not exposed to sun light properly.
• Nutritional deficiency of calcium and
phosphate may produce similar clinical
picture
• Malabsorption of vitamin ( Obstructive
jaundice and steatorrhea).
• High phytate content in diet reduce the
absorption of vitamin.
• Abnormal Vit.D activation.

31. Osteomalacia
• Greek Words
• Osteo = bone.
• Malakia = soft.
• Insufficient mineralization and increased
osteoporosis, more prone to fractures.
• Serum calcium and phosphate levels are low.
• Serum alkaline phosphatase is markedly
increase.

32. Rickets
• A deficiency of vitamin D or an inability to
utilize vitamin D may lead to a condition
called rickets.
• In this condition there is weakening and
softening of the bones due to extreme loss of
calcium.

33. Different types of rickets
• 1. Classical Vitamin D rickets can be cured by
giving vitamin D.
• 2.The Hypophosphatemic rickets is due to
defective resorption of phosphate from kidney
• 3.Vitamin D and phosphate is used in treatment.
• Vitamin D resistant rickets found with fanconi
syndrome in which renal resorption of
bicarbonate , phosphate , glucose , amino acids
are deficient.

34. Cont…….
• Renal rickets : In kidney diseases even if vitamin
D is present calcitriole is not formed.
• This will respond to calcitriole administration.
End organ refraction to vitamin D( Bone disease)
Respond to mega dose of calcitriole.

35. Hyper Vitaminosis D
• Doses above 1500 IU/day for long period
causes toxicity.
• Symptoms are : weakness, polyurea, Intense
thirst, difficulty in
speaking, hypertension, weight loss.
• Calcification of soft tissue called calcinosis
especially in vascular and renal tissue.
• Excessive sunlight does not causes Hyper
Vitaminosis D.

36. Vitamin K
• RDA------70 mcg ( 50- 100 mcg )
• FAT Soluble
• Sources : Cabbage, cauliflower, spinach, other
green vegetables, and cereals.
• Major role is in blood clotting.

37. Vitamin K
• ACTIVE FORM ----- :
• PHYLLOQUINONE ( PLANTS )----K1
• MENAQUINONE ( ANIMALS )----K2
• MENADIONE ( SYNTHETIC FORM)---K3

38. Absorption and storage
• Absorption of vitamin K occurs in the
intestinal mucosa along with chylomicrons.
• Bile salts are required for the normal
absorption.
• Vitamin K may derived from diet or intestinal
bacterial synthesis.
• It is stored in the liver and transported in the
plasma along with beta lipoprotein.

39. FUNCTIONS
• POST TRANSLATIONAL MODIFICATION OF
VARIOUS BLOOD CLOTTING FACTORS LIKE
, II,VII, IX, AND X.
• THIS IS DONE BY CARBOXYLATION OF
GLUTAMIC ACID RESIDUE WITH THE
FORMATION OF GAMA-CARBOXYGLUTAMATE
• CARBXYLATION OF BONE AND KIDNEY
PROTEIN

40. Biochemical role of Vitamin K
• Vitamin K is necessary for the coagulation.
• Factors dependent on Vitamin K are
1.Factor II ( prothrombin);
• 2.Factor VII
• 3.Factor IX ( Charismas factor).
• 4. Factor X ( Stuart power factor ).
• All these factors are synthesized in the liver
as inactive zymogen.

41. • Zymogens undergo post translational
modification ( Gama carboxylation of
Glutamic acid residues ).
• Gama carboxy glutamic acid synthesis require
vitamin K as co factor.
• This is also needed for the functional activity
of osteocalcin(osteoblasts of bone) as well as
structural proteins of kidney, lung and spleen

42. Vitamin K dependent Carboxylase
• It is microsomal enzyme.
• It requires reduced vitamin K , oxygen
, NADPH and CO2 .
In this process vitamin passes through a cycle.
This process is inhibited by warferin and
dicomurol.

43. DIETARY DEGICIENCY
• VITAMIN K –Deficiency is unusual unless the
bacterial flora in gut decreased by antibiotics
or other drugs or in new born babies.
• TOXICITY : Vitamin K can produces hemolytic
anemia due to toxic effects on the membrane
of red cells.

44. Clinical manifestations
• 1. Hemorrhagic disease of new born is due to
Vit. K deficiency.
• Premature infants are having great chance to
develop the deficiency state, this is due to
lack of hepatic stores, limited oral intake, and
absence of intestinal bacterial floora.
• Prophylactic dose in new born is 1mg
Menadione.

45. Warferin and Dicomurol.
• Competitively inhibit the gama carboxylation.
• They are structurally similar to vitamin K.
• They are widely used as anti coagulant drugs.
• Treatment with warferin in pregnant women
may lead to foetal bone abnormalities known
as foetal warferin syndrome.

46. Hyper Vitaminosis K
• Hemolysis
• Hyperbilirubinemia
• Kernicterus
• Brain damage.
• Due to administration of large amount of
vitamin K.

47. VITAMIN E
• RDA : 10 mg
• Active form –alpha tocoferol.
• Functions : Antioxidant in prevention of - non
enzymatic oxidation of cell component by
molecular oxygen and free radicals. Helps in RBC
formation and the use of vitamin K, promotes
functions of healthy circulatory system
• Sources : Vegetable oil, liver, egg and wheat
germ oils , nuts and green leafy vegetables.

48. Deficiency
• In premature infants
• With defective lipid metabolism in adults.
• Toxicity :
• Very less toxic .

49. Prevention of chronic disease
• Vitamin C , vitamin E and beta carotene are
known as antioxidant vitamins.
• Supplementation of the diet with these
vitamins, decrease the incidence of chronic
diseases such as coronary heart disease and
cancers.
• The common chemical property though to be
central to their ability to inactivate toxic
oxygen free radicals

50. Reactive oxygen radical arise from
1. By product of normal metabolism.
2.By exposure to sun light.
3.Ozone
4.Tobacco smoking.
5.Environmental pollution.

51. Free radicals……..
• Free radicals are known to damage lipid
membrane, protein and cellular DNA.
• Free radicals are thought to play a role in the
development of heart and lung disease, cancer
and aging.
• GliSODin activates the most powerful anti
oxidant known , the body’s own internal
defense system, including superoxide
dismutase( SOD ), catalase and glutathione
peroxidase(Gpx).

52. Inter-relation of Vitamin E and
Selenium
• Selenium is present in glutathione
peroxidase, an important enzyme that
oxidizes and destroys the free radicals.
• Selenium has found to decrease the
requirement of Vitamin E and vice versa.
• They act synergistically to minimize lipid
peroxidation.