Vitamins are nutrients which are required in micro grams.They are essential for normal function of the body.They act as cofactors and prosthetic groups for enzymes

1. ALL ABOUT VITAMINS
VITAMIN B6, B7, B12 AND
FOLIC ACID
FEBA SHAJI
I MSc Biochemistry
SBS
.

2. INTRODUCTION
Vitamins are nutrients which are required
in micro grams
They are essential for normal function of
the body
They act as cofactors and prosthetic
groups for enzymes

3. VITAMIN B6
Includes pyridoxal and pyridoxamine.
Pyridoxal phosphate is coenzyme to more
than 100 reaction involving amino acid,
especially transamination and
decarboxylation.
RDA : 1.4 - 2.0 mg/day

4. DISCOVERY OF VITAMIN B6
• It was discovered by Hungarian born scientist
Paul Gyorgy in 1934 who was conducting
research on skin diseases in rats.
• Rat fed on semi synthetic diet (with thiamine
and riboflavin) developed rat acrodynia and it
was cured by Vitamin B6.
• Samuel Lepkovsky isolated and crystallized
Vitamin B6 in 1938.
• In 1939 Leslie Harris, Karl Folker and Richard
Kuhn gave structure.
• Esdmond Snell in 1942 discovered pyridoxamine.

5. PAUL
GYORGY

6. PHYSICAL PROPERTIES
• Molecular formula : C8H12NO3
• Molecular weight : 169.17784 g/mol
• 4,5-bis(hydroxymethyl)-2-methyl pyridin-3-ol
• Color : white to crystalline powder
• Taste : bitter taste
• Boiling point : sublime
• Melting point : 159 - 162ᵒ C
• Solubility : 220000 mg/l
• It is photosensitive should be kept between 15 -
30ᵒ C.

7. STRUCTURE OF VITAMIN B6

8. SOURCES OF VITAMIN B6
• Wheat germ
• Meat
• Potatoes
• Nuts and seeds
• Egg yolks etc.

9. BIOSYNTHESIS
• Made in green plants and microorganisms
from 3 - carbon intermediates of glycolysis
e.g., glyceraldehyde-3-phosphate.
• In E.coli glycerol can furnish all the carbon
atoms.

10. METABOLISM
• In liver ingested pyridoxine is phosphorylated
by specific kinases.
• Then oxidized to pyridoxal phosphate by a
specific flavin enzyme.
• Approximately 90% of B6 administered to
humans is oxidized to 4- pyridoxic acid and is
excreted in this form.

11. FUNCTIONS OF VITAMIN B6
• The conversion of homocysteine to cysteine.
• For energy production from amino acids so
they are also known as energy releasing
vitamins.
• Synthesis of neurotransmitters like serotonin
and norepinephrine.
• Synthesis of sphingolipids required for the
formation of myelin sheath.

12. • Synthesis of delta amino levulinic acid a
precursor of heme.
• Pyridoxal phosphate is also an important
component of glycogen phosphorylase.(It is
covalentaly linked to lysine residue and
stabilise the enzyme)
• To convert tryptophan to nicotinic acid(NAD).

13. • Tryptophan serotonin
• Histidine histamine
• Tryptophan NAD
• Glycine
ALA heme
SuccinylCoA

14. DEFICIENCY SYMPTOMS OF VITAMIN
B6
• Low level of vitamin B6 lead to
hyperhomocysteinanemia which is thought
to be a risk factor for ischemic heart disease.(
conversion of homocysteine to cysteine)
• In mild deficiency, symptoms like irritability,
nervousness and depressions arise.(formation of
myelin sheath)
• In severe deficiency, symptoms like
peripheral neuropathy and convulsions arise.

15. • Deficiency cause sideroblastic anemia which
is characteristically a microcytic anemia seen
in presence of high serum iron.(synthesis of heme
precursor)
• Deficiency leads to decrease glucose
tolerance.(as B6 is needed in glycogen phosphorylase and
they also have some direct effect on glucocorticoids)

16. TOXICITY
Vitamin B6 (pyridoxine) causes
neuropathy at intakes of 1000 mg per day
or more, which is about 800 times the
daily intake from foods. There have also
been occasional reports of toxicity at
intakes of 100-300 mg per day.

17. HOW DOES THIS DEFICIENCY ARISE?
• Poor intake, malabsorption or increased
requirement(old age).
• In some infants, when ingesting baby food.
• Intake of contraceptives.
• There is a increased requirement during
pregnancy and lactation.
• Intake of several drugs like isoniazide (as in
TB).

18. HOW IS THE DEFICIENCY DIAGNOSED?
• By activation of red cell amino
transferase by pyridoxine phosphate.
• By measurement of plasma
concentration of pyridoxine phosphate.
• By tryptophan assay.

19. VITAMIN B7 ( BIOTIN )
Co discovered by Dean Burk an American
biochemist.
In 1936 a crystalline growth factor for yeast
was isolated from egg yolk a few years earlier a
factor necessary for the growth and respiration
of Rhizobium had been termed coenzyme R.
Later it was known that both were biotin.
In 1940 biotin was established as anti-egg-
white injury factor.
RDA : 10 micrograms/day

20. DEAN BURK

21. PHYSICAL PROPERTIES
• Molecular formula : C10H16N2O35
• Molecular weight : 244.310 g/mol
• Melting point : 232ᵒ C
• Solubility : 220 mg/l (at 25ᵒ C)
• Colorless thin needle like in water

22. STRUCTURE OF BIOTIN

23. SOURCES OF BIOTIN
• Egg yolk
• Liver
• Yeast
• Nuts
• Berries

24. BIOSYNTHESIS OF BIOTIN
• Oxidative cleavage of oleic acid
• Addition of Co A
• Removal of acetyl Co A and addition of Co A
• Addition of alanine and removal of carbon
atom
• Transfer of amino group
• Addition of CO2 at expense of energy
• Addition of sulphur atom

26. METABOLISM
• Biocytin (biotinyllysine) is liberated from
biotin holoenzymes by proteolysis.
• Biocytinase in liver and blood liberates biotin
and lysine.
• In mammals biotin sidechains undergoes
usual beta oxidation, yielding 2 moles of
acetyl CoA, the fate of the ring structure is
unknown.

27. FUNCTION
• It is a prosthetic group of many carboxylase
enzymes
• Pyruvate CoA carboxylase needed for synthesis
of OAA for gluconeogenesis and replenishment
of citric acid cycle
• Acetyl CoA carboxylase is needed for fatty acid
biosynthesis
• Propionyl CoA carboxylase is needed for amino
acid metabolism(methionine, leucine and
valine)

29. HOW DOES THE DEFICIENCY ARISE ?
• Egg white contains avidin protein, it binds to
biotin and renders it unavailable for binding
to enzymes. So intake of uncooked egg leads
to deficiency symptoms
• Reduction in intestinal bacteria.

30. TOXICITY
Vitamin B7 (biotin) is not known to be toxic.
However, there is one case report of life-
threatening 'eosinophilic pleuropericardial
effusion' in an elderly woman who took a
combination of 10,000 mcg (= 10 mg)/day
vitamin B7 (biotin) and 300 mg/day vitamin B5
(pantothenic acid) for two months (36)

31. FOLIC ACID
Folic acid (conjugate base folate) is a B vitamin.
Folic acid is made and used in fortified
foods and supplements on the theory that it is
converted into folate. However, folic acid is
an oxidized form, not significantly found in
fresh natural foods. To be used it must be
converted to tetrahydrofolate (tetrahydrofolic
acid) by dihydrofolate reductase (DHFR)
RDA : 50 micrograms/day

32. DISCOVERY OF FOLIC ACID
Folic acid and its role in human biochemical
function was first identified by researcher Lucy
Wills in 1931. She found that this vitamin was
needed to prevent anaemia during pregnancy Dr
Wills demonstrated that anaemia could be
reversed by brewers yeast. It was first extracted by
Mitchell and team in 1941. Bobstokstad isolated
pure crystals.
This led to the synthesis of aminopterin in 1943
first ever anti-cancer drug.

34. PHYSICAL PROPERTIES
• Molecular formula : C19H12N7O6
• Molecular weight : 441.397 g/mol
• Solubility : 1.6 mg/l at 25ᵒC
• Melting point : 250ᵒC
• Colour : orange - yellow needle like crystals

35. STRUCTURE OF FOLIC ACID

36. SOURCES OF FOLIC ACID

37. BIOSYNTHESIS OF FOLIC ACID

38. METABOLISM
• Folic acid usually occurs as polyglutamate
derivatives .
• These are taken up by mucosal cell and excess
glutamate is removed by conjugase.
• Free folic acid is then reduced to
tetrahydrofolate by enzyme dihyrofolate
reductase and it is circulated as N5– methyl
derivative of tetrahydrofolate.
• Foic acid is stored as polyglutamate derivative of
tetrahydrofolate in liver.

40. FUNCTIONS OF FOLIC ACID
• Derivatives of tetrahydrofolate are used in the
biosynthesis reactions of
• Choline
• Serine
• Glycine
• Purines
• dTMPs

41. DEFICIENCY SYMPTOMS
• Inhibition of DNA synthesis due to lack of
purines and dTMPs.
• This leads to S stage arrest of cell cycle and
formation of ‘megaloblastic’ change in size
and shape of nuclei of rapidly dividing cells.
• During pregnancy it leads to increased
incidence of neural tube defects in foetus.
• Hyperhomocysteinemia occurs leading to
CVD.

42. HOW DEFICIENCY OCCURS ?
• Poor diet, increased requirement.
• Drugs that interfere with folate metabolism.
Example : Methotrexate(folate antagonist),
Cotrimoxazole(inhibit formation of active
tetrahydrofolate).
• In alcoholics poor intake and antagonistic
effect of alcohol is seen.
• Folates are susceptible to oxidation, more
than 50% of folate is destroyed by cooking

43. HOW IS DEFICIENCY DIAGNOSED?
• Folate deficiency is diagnosed by
measurement of serum or red cell folate
content.
• Serum folate content is affected by short
term fluctuations in dietary intake.
• Red cell folate indicates tissue store more
accurately.

44. TOXICITY
There is no health risk associated
with folate intake from food. However, there is
risk of toxicity from folic acid found in dietary
supplements and fortified foods. Folic acid is
used to treat a folate deficiency. However,
a folate deficiency is virtually indistinguishable
from a vitamin B12 deficiency.

45. VITAMIN B12
Vitamin B12 is also known as cyanocobalamine,
Bedoz, cyanoject, cobione.
It is an important vitamin used as a co enzyme
Like in enzymes involved in the synthesis of
methionine from homocysteine and conversion
of methyl malonic acid to succinic acid.
RDA : 2 – 3 microgram/day

46. DISCOVERY

47. PHYSICAL PROPERTIES
• Molecular weight : 1356.373117g/mol
• Solubility : 12500mg/l
• Boiling point and melting point is greater
than 300ᵒC
• It is tasteless and odorless
• Dark red crystals or amorphous powder

48. STRUCTURE OF VITAMIN B12

49. SOURCES OF VITAMIN B12
Store of B12 is high in body so deficiency occurs 5
years from when the dietary supply is removed.

50. BIOSYNTHESIS

51. ABSORPTION OF VITAMIN B12

52. FUNCTIONS OF VITAMIN B12
• It is an important co enzyme for two enzymes
• It help in synthesis of methionine from
homocysteine as it a coenzyme for methionine
synthase
• Methionine is then converted to S -
adenosylmethionine which is methyl donor for
RNA and DNA methylation
• It help in the conversion of methyl malonyl CoA
to succinyl CoA (as it is present in the enzyme L - methyl
malonyl CoA mutase)

53. • Needed for myelin sheath synthesis [Methionine
choline(methyl transfer) ethanolamine
sphingomyelins].

55. DEFICIENCY DISEASES
• Causes sub acute combined degeneration of
the spinal cord.
• Cause pernicious anaemia.
• Cause hyper segmentation of neutrophils,
macrocytic anaemia, thrombocytopenia and
megaloblastic changes in bone marrow.

56. REASONS FOR DEFICIENCY
• In pernicious anaemia gastric parietal cells are
destructed by autoantibodies leading to lack in
intrinsic factor.
• Abnormal bacterial flora which inhabits
intestine in case of diseases use excess vitamin
B12.
• Rare infestation with Diphyllobothrium
latum(fish tapeworm).
• Drugs which interfere with B12 metabolism.
• HIV patients develop B12 deficiency due to
malabsorbption.

57. TOXICITY
No toxic or adverse effects have been
associated with large intakes of vitamin
B12from food or supplements in healthy people.
Doses as high as 2 mg (2,000 μg) daily by
mouth or 1 mg monthly by intramuscular (IM)
injection have been used to treat pernicious
anemia without significant side effects

58. REFERENCES
Handbook of Clinical Biochemistry, 2nd edition.
R Swaminathan
- World Scientific Publishing Co. Ltd.
Functional Biochemistry in Health and
Diseases.
Eric Newsholme and Tony Leech
- Wiley Blackwell publication.
http://pubchem.ncbi.nlm.nih.gov/

59. Principles of Biochemistry (Mammalian
Biochemistry) 7th edition
Smith, Hill, Lehman, Lefkowitz, Handler and
White
- McGraw-Hill International Edition
Text book of Biochemistry with clinical
correlations
Thomas M Devlin
Biochemistry
David James and Nigel Hooper