Vitamin B12, COBALAMIN

COBALAMIN

1. VITAMIN B12
COBALAMIN
Dr. Muhammad Sarfraz
M.B.B.S., M.Phil.(Pharmacology)
Senior Demonstrator
Quaid-e-Azam Medical College
Bahawalpur, pakistan.


1

2. Vitamin B12
COBALAMIN



2

3. Vitamin B 12
COBALAMIN


•Vitamin B
12, cobalamin

•water-soluble vitamin
3

4. Cobalamine
VitaminB
12

5. Chemistry
It is made up of Tetrapyrrole
ring system called as corrin
ring with a central cobalt (Co)
atom.

7. 7

8. Vitamin B
12 absent in plant food

9. 3-4
μg/day.
Storage in
liver
4-5 mg

10. Vitamin B
12 Absorption Requires Two Binding
Proteins
•Vitamin B12 is absorbed
• Bound to intrinsic factor
•A small glycoprotein
• Secreted by the parietal cells of the
gastric mucosa
10

11. Vitamin B
12 Absorption Requires Two
Binding Proteins
Gastric Acid And Pepsin
Release The Vitamin From
Protein Binding In Food
11

12. Vitamin B
12 Absorption Requires Two
Binding Proteins
Bind To Cobalophilin
A Binding Protein
Secreted In The Saliva
12

13. Vitamin B
12 Absorption Requires Two
Binding Proteins
In The Duodenum
Cobalophilin
Is
Hydrolyzed 13

14. Vitamin B
12 Absorption Requires Two
Binding Proteins
Releasing The Vitamin
Bind To
Intrinsic Factor
14

15. Vitamin B
12 Absorption Requires Two
Binding Proteins
Vitamin B
12 Is Absorbed From The
Distal Third Of The Ileum
Via
Receptors
That Bind The Intrinsic Factor-vitamin
B
12 Complex
15

16. Vitamin B
12 Absorption Requires Two
Binding Proteins
Neither FREE INTRINSIC
FACTOR
NOR
FREE VITAMIN
IS ABSORBED
16

17. Vitamin B
12 Absorption Requires Two
Binding Proteins
•INTO THE GENERAL
CIRCULATION
CARRIED BY
B12-BINDING PROTEINS.

17

18. Vitamin B
l2 combines with intrinsic
factor to form Vitamin B
12- IF
complex.
Vitamin B
12 intrinsic factor
complex is absorbed in the ileum.
In the illeal cells the intrinsic
factor is released and the B
12 is
transferred to a plasma transport
protein transcobalamin II.

20. Unlike other
water soluble
vitamins,
vitamin B
12 is
stored in the
liver and other
tissues
Whole liver
contains about
4-5 mg of B
12,
which is
sufficient for 2-
3 years.
Vitamin B
12 is the only water soluble vitamin stored in liver

21. Methyl cobalamin
Deoxy
adenosylcobalamin

23. Vitamin B
12-Functions
VITAMIN B
12
ACT AS COENZYME .
•METHYL COBALAMIN
COENZYME OF
Methionine Synthase

23

24. 24

25. Vitamin B
12-Functions

DEOXY ADENOSYLCOBALAMIN

COENZYME OF

METHYL MALONYL -COA MUTASE

25

26. Methylmalonyl (COA)
Produced During The
Degradation of
Isoleucine, Valine, Threonine, And
Methionine
• AND
• Fatty Acids With Odd Numbers Of
Carbon Atoms
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27. © 2008 Thomson - Wadsworth

28. 28

29. © 2008 Thomson - Wadsworth

30. FOLATE TRAP

31. FUNCTIONS OF VIT B12
•WHEN THE VITAMIN IS DEFICIENT,
UNUSUAL FATTY ACIDS ACCUMULATE
•AND BECOME INCORPORATED INTO
CELL MEMBRANES , INCLUDING
THOSE OF THE NERVOUS SYSTEM
31

32. Vitamin B 12
COBALAMIN
KEY ROLE
NORMAL FUNCTIONING OF
THE BRAIN AND NERVOUS
SYSTEM
FORMATION OF BLOOD
INVOLVED IN DNA
SYNTHESIS AND
REGULATION
32

33. Vitamin B 12
COBALAMIN
FATTY ACID SYNTHESIS AND
ENERGY PRODUCTION

•ONLY BACTERIA HAVE THE
ENZYMES REQUIRED FOR ITS
SYNTHESIS
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34. Causes
•Nutritional
•Decrease in
absorption
•IF deficiency
•Gastric atrophy
•Pregnancy
•Fish tapeworm

35. Vitamin B 12

•FOUND ONLY IN FOODS OF
ANIMAL ORIGIN


•STRICT VEGETARIANS ARE AT
RISK OF DEVELOPING B
12
DEFICIENCY
35

36. Vitamin B 12

•Largest And Most
Structurally Complicated
Vitamin
•Produced Industrially
Only Through
Bacterial Fermentation
synthesis
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37. EFFECTS OF COBALAMIN
DEFICIENCY
PRONOUNCED
IN
•RAPIDLY DIVIDING CELLS ,
SUCH AS THE
ERYTHROPOIETIC TISSUE
OF BONE MARROW
•MUCOSAL CELLS OF THE
INTESTINE

37

38. Vitamin B
12-Deficiency
Hamatopoitic
•Megaloblastic
anemia
•Pernicious anemia

38

39. PERNICIOUS ANEMIA
• AUTOIMMUNE DISEASE
• PARIETAL CELLS OF THE
STOMACH
•DESTROYED
•NO
INTRINSIC FACTOR
PRODUCTION
39

40. Vitamin B
12-Deficiency
Neurological
•Numbness and tingling
of the hands and feet

•Subacute combined
degeneration

40

41. 41

42. Vitamin B
12-Deficiency
Others
•Hyperhomocysteine
mia

•Achlorhydria

42

44. Pernicious Anemia

Disease Is Treated By Giving
High-dose B12
Intramuscular
Injection
Of Cyanocobalamin
44

45. Pernicious Anemia

THERAPY
MUST
CONTINUED
THROUGHOUT THE LIVES
OF PATIENTS WITH
PERNICIOUS ANEMIA

45

46. Folate trap hypothesis
© 2008 Thomson - Wadsworth

47. Function of folic acid
47

48. FOLATE TRAP

49. •Methylated Form
•Cannot Be Converted Directly To
Other Forms Of Tetrahydrofolate
•Folate
Trapped In The
N5-methyl Form
FH4.CH3
49

50. FOLATE TRAP

51. Folate trap hypothesis
The Levels Of The Other Forms
Decrease.
Cobalamin Deficiency Leads To
Deficiency Of The Other
Tetrahydrofolate Forms
Needed In Purine And TMP
Synthesis 51

52. 52

53. VITAMIN B
12 DEFICIENCY CAUSES
PERNICIOUS ANEMIA

•PATIENTS WHO FAIL TO ABSORB
THE VITAMIN FROM THE
INTESTINE.
•MOST OFTEN DUE TO REDUCED
SECRETION OF GASTRIC ACID
AND LESS EFFICIENT
ABSORPTION OF VITAMIN B 12
FROM FOODS.
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54. Pernicious Anemia

•AUTOIMMUNE DESTRUCTION
OF THE GASTRIC PARIETAL
CELLS
•RESPONSIBLE FOR THE
SYNTHESIS OF A
GLYCOPROTEIN CALLED
INTRINSIC FACTOR .
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55. Pernicious Anemia

•LACK OF INTRINSIC
FACTOR PREVENTS THE
ABSORPTION OF VITAMIN
B12
•RESULTING IN
PERNICIOUS ANEMIA.
55

56. Pernicious Anemia
•PATIENTS WITH COBALAMIN
DEFICIENCY ARE USUALLY
ANEMIC, BUT LATER IN THE
DEVELOPMENT OF THE DISEASE
•THEY SHOW
NEUROPSYCHIATRIC SYMPTOMS
•CNS EFFECTS ARE
IRREVERSIBLE
56

57. Schilling test
© 2008 Thomson - Wadsworth

58. Schilling test
•PHYSIOLOGIC BASIS BEHIND THE
SCHILLING TEST
•If you are able to absorb B12
normally,
•you will absorb it through your
intestinal cells
• it will enter bloodstream
•where it will circulate
throughout body
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59. Schilling test

•If you can’t absorb it
correctly
• it will not be absorbed
through gut mucosa
• excreted in feces
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60. Schilling test
•Saturate Any Open B12 Binding
Sites Throughout The Body

•The Patient Gets
Injections Of Regular B12 At The
Same Time

•Then we Use oral Radioactive B12
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61. In a patient who CAN absorb B12
properly, here’s what happens:
Give IM B12 To Saturate Any
Empty B12 Binding Sites
Give Patient A Drink Of
Radioactive B12

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62. In a patient who CAN absorb B12
properly, here’s what happens:
Wait a while and see if the
B12 is absorbed through the
gut mucosal cells and
circulates around the body
in the blood
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63. In a patient who CAN absorb B12
properly, here’s what happens:

It won’t have many places to
drop off B12 (because you’ve
thought ahead to block all those
sites) – so most of the B12 will
just stay in the blood and get
excreted out in the urine

63

64. In a patient who CAN absorb B12
properly, here’s what happens:
You measure the
radioactivity of the urine
 and that tells you how
much B12 made it through
the gut (was absorbed
through the gut) and got
into the blood
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65. But in a patient who CAN’T absorb
B12 properly, here’s what happens:
•Give IM B12 to saturate any
empty B12 binding sites

•Give patient a drink of
radioactive B12.
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66. But in a patient who CAN’T absorb
B12 properly, here’s what happens:
•Wait a while and see if the B12 is
absorbed through the gut mucosal cells
and gets into the blood
• If the patient can’t absorb B12, then
the B12 won’t get through the gut
mucosal cells, and it will just stay in
the gut and excreted in the feces
(instead of in the urine)
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67. Then ?
•Then, you can perform the test again, giving
the patient some intrinsic factor this time to
see if the B12 will be absorbed.
• If there is now radioactive B12 in the urine,
you know that the problem was lack of
intrinsic factor.
•If the urine still doesn’t have radioactive B12,
then you need to figure out some other cause.
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70. Other Tests To Diagnose Pernicious
Anemia
•Megaloblastic Anaemia
•Low levels of B12 in blood
•Antibodies Against
Intrinsic Factor
Parietal Cells
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71. Other Tests To Diagnose Pernicious
Anemia
High Levels Of
Homocysteine
And
Methyl Malonic Acid
In Blood
© 2008 Thomson - Wadsworth