1. Vitamin B6 (Pyridoxine), Protein Burner

2. Introduction Vitamin B6 was discovered in the 1930s.
Vitamin B6 occurs in several forms, all of which can be
converted to the most active coenzyme form, Pyridoxal
Phosphate (PLP).
PLP has a vital role in catalyzing dozens of chemical
reactions in the body.
Vitamin B6 is unusual as a B vitamin in that it is so
extensively stored in muscle tissue.

3. Cont. Sources: Whole grains, organ meats, eggs and legumes.
Requirements:
Adults: 2.2mg/day
Children:1.2mg/day
Infants: 3mg/day

4. Cont.

5. B6 Vitamin B6 consists of three substituted pyridines:
Pyridoxal: which carries an aldehyde group (–CHO) at C-4,
Pyridoxol : Is the corresponding alcohol (–CH2OH), and
Pyridoxamine: The amine (–CH2NH2).

7. 4-Pyridoxic acid

8. Metabolism of pyridoxine-related
compounds in mammals

9. Cont. Almost all conversion reactions involving amino acids
require pyridoxal phosphate, including:
Transaminations,
Deamination,
Decarboxylations,
Dehydrogenations,
Transsulfuration and Condensation e.t.c.

10. Cont.
Glutamate
dehydrogenase
Glutamate
dehydrogenase

11. Reaction catalyzed by glutamate dehydrogenase.

12. Decarboxylation Process of removal of carboxilic functional group is
known as decarboxylation e. g:
Methionine Homocysteine
Cystathionine
Cysteine Homoserine
Serine
PLP
Cystathionine synthase
Decarboxylase
PLP
Taurine

13. Cont. Glycogen phosphorylase, the enzyme for glycogen
degradation, also contains pyridoxal phosphate as a
cofactor.
Glucose is stored as glycogen in muscle tissue to
Provide energy on-site and when it is first needed.
PLP is a coenzyme to the enzyme glycogen
phosphorylase, which catalyzes the release of glucose
from glycogen.
In another process, known as gluconeogenesis, PLP
is needed to convert amino acids to glucose.

14. Vitamin B6 assists energy production from protein and carbohydrates.

15. Cont. Many important neurotransmitters are synthesized
using PLP-dependent enzymes are:
Serotonin,
Dopamine,
Gamma-aminobutyric acid (GABA), and
Norepinephrine.
Tryptophan Niacin.
Homocysteine cysteine
PLP
PLP

16. Vitamin B6, folate, and vitamin B12 convert the undesirable homocysteine to the useful amino acids cysteine and methionine.

17. Cont.
PLP can help:
PLP also functions in the synthesis of heme, a part of hemoglobin,
Some forms of vitamin B6 help hemoglobin pick up and release oxygen and
Help in nucleic acid synthesis.

18. Cont.

19. Relation between hypoglycemia and alcohol intoxication
Ethanol has been a part of the human diet for
centuries.
Excess consumption leads to toxication.
Cytoplasmic Metabolism:
Ethanol cannot be excreted and must be metabolised
by liver (mainly).
Alcohol
CH3CH2OH +NAD CH3CHO (Acetaldehyde)
(Ethanol) Dehydrogenase

20. Cont.

21. Cont. Deficiency symptoms:
Hypochromic microcytic anaemia, glossitis, pigmented
Scaly dermatitis similar to pellagra, numbness and
tingling sensations in the extremities, Irritability,
depression and convulsive seizures.
Tuberculosis patients who are on long term therapy
With anti-tuberculosis drug INH (isonicotinic acid
hydrazine) suffer from B6 deficiency.

22. Cont. This drug has a structure similar to B6 and
antagonises the action of B6.
Hence, along with INH, they have to be given large
doses of B6.
INH is a drug used to treat tuberculosis and
supplemental vitamin B6 must be given during
treatment.
B6 deficiency occurs in women taking oral
contraceptives.

23. Cont. The drug penicillamine used in: Rheumatoid arthritis,
Wilson’s disease and
Cystinuria e.t.c.
Deficiency occur so, supplementation is required.

24. Thank you

25. Vitamin B12

26. Introduction B12, vitamin (cobalamin, cyanocobalamin,
hydroxocobalamin).
A component of the vitamin B complex essential to the
growth and repair of all body cells.
Vitamin B12 is a generic term for several cobalt-
containing compounds, of which cyanocobalamin is
the most stable form.
Synthetic vitamin B12 contains a cyanide group not
found naturally.

27. C63H90N14O14PCo

29. CN, CH3 or Adenosine

31. Cont. Structure of the cobalamin family of compounds. A
through D are the four rings in the corrinoid ring
system.
The B ring is important for cobalamin binding to
intrinsic factor.
If R = -CN, the molecule is cyanocobalamin
(vitamin B12); if R = 5'-deoxyadenosine, the molecule is
adenosylcobalamin; if R = -CH3, the molecule is
methylcobalamin.

32. Cont. Sources: Liver, meat, fish, eggs and milk. Requirements:
Children :2µgm/day
Adults :3µgm/day
Pregnancy and Lactation:4µgm/day

35. Cont. Absorption, transport, and cellular uptake of vitamin B
12 in humans.
IF, Intrinsic factor; TCII, transcobalamin II; circles in the
membranes of the ileal mucosal cell and peripheral
tissues represent transport molecules for IF/B12 and
TCII/B12,respectively.

36. Cont. Cobalamin Coenzyme forms are: Methylcobalamin and
Deoxyadenosyl cobalamin.

39. Function

40. Cont. In addition to its growth and repair abilities, the
vitamin is essential for the formation of mature red
blood cells and central nervous system function.
It interacts with folic acid coenzymes and is involved
in the synthesis of DNA and methionine, an essential
amino acid.
Experiments with laboratory mice suggest that
vitamin B12, when combined with vitamin C, may
inhibit the formation of cancerous tumors in mice.

41. Cont. B12 along with folic acid is required for the
development of RBCs beyond megaloblastic stage.
It acts as coenzyme for the mutase enzyme which
Converts methyl malonyl coA into succinyl coA.
It is involved in the conversion of ribonucleotides to
deoxyribonucleotides.

42. cont.
Deficiency:
Result from intestinal malabsorption and poor dietary
intake.
Symptoms:
Megaloblastic anemia, Glossitis and inflammation of
mouth, methyl malonic aciduria.

43. Treatment of Cobalamin deficiency
Route of administration
Initial treatment
Maintenance treatment
Intravenous
1000 µg/day for 1 week
1000µg/month for Pernicious anemia throughout life
Oral
1000 µg/day for 1 month
µg/day for Food Cobalamin malabsorption; 1000µg/day for Pernicious anemia
Andres et. al.; Canadian Medical Association Journal; 2004; 171 (3) –

44. Thank you.

45. Folate (folacin)

46. Introduction Folate, the anion of folic acid, is made up of three
different components: a pteridine derivative, 4-
aminobenzoate, and one or more glutamate residues.
After reduction to tetrahydrofolate (THF), folate serves
as a coenzyme.
Folate deficiency is relatively common, and leads to
disturbances in nucleotide biosynthesis and thus cell
proliferation.

47. Cont. As the precursors for blood cells divide particularly
rapidly, disturbances of the blood picture can occur,
with increased amounts of abnormal precursors
for megalocytes (megaloblastic anemia).
Later, general damage ensues as phospholipid
synthesis and the amino acid metabolism are affected.
In contrast to animals, microorganisms are
able to synthesize folate from their own components.

48. Cont. The growth of microorganisms can therefore be
inhibited by sulfonamides, which competitively inhibit
the incorporation of 4-aminobenzoate into folate.
Since folate is not synthesized in the animal organism,
sulfonamides have no effect on animal metabolism.

49. cont. Composed pteridin ring attached to para amino
benzoic acid(PABA) and conjugated with glutamic acid
residues.

50. Cont. Sources: Fresh green vegetables, liver, whole grains, meats
and legums.
Requirements:
Children :300µg/day
Adults :400µg/day
Pregnancy and lactation :800µg/day

51. Absorption, transport and storage
Tetrahydrofolate (THF)
Tetrahydrofolate (THF)

52. Tetrahydrofolate (THF)

55. Tetrahydrofolic acid and the one-carbon substituted folates.

56. Cont. 5-Formyl-tetrahydrofolate is more stable than folate
and is therefore used pharmaceutically in the agent
known as folinic acid and in the synthetic (racemic)
compound leucovorin.

57. Uses of Folic acid Folic acid is required for the synthesis of:
Certain amino acids,
Purines, and
Pyrimidine:Thymine.

58. One carbon metabolites compounds

59. The origins of the atoms in the purine ring are indicated.

60. Glycine, serine, ethanolamine and choline:

61. Cont. The coenzyme form :Tetrahydro Folic acid(FH4)
FH4: Carrier of one carbon and it is involved in one
carbon transfer reactions.
One carbon may be in the form of Formyl (-CHO) group.
Tryptophan FH4
Formate N10 formyl FH C-2 purine ring

62. Cont. Histidine FIGLU N5N10 methylene FH4 C-8 purine ring
Glycine N5N10 methylene FH Thymidine
monophosphaate

64. Cont.
Deficiency:
Results from low dietary intake, malabsorption syndrome
and during pregnancy.

65. Cont. Deficiency leads to megaloblastic anemia and growth failure.
FH4 required for purine ring synthesis which again required
for the synthesis of DNA and RNA.
FIGLU excretion test: In the deficiency of folic acid,there
is no FH4 so formaminoglutamate accumulates in the blood
and excreted in the urine.This is one of the test to detect
the megaloblastic anemia whether it is due to folic acid or
vitamin B12 deficiency.

66. Folic acid Deficiency Promotes Birth Defects Such As Spina Bifida
Spina bifida is one of a class of birth defects
characterizeed by the incomplete or incorrect
formation of the neural tube early in development.
In the united states, the prevalence of neural-tube
defects is approximately 1 case/1000 births.
A variety of studies have demonstrated that the
prevalence of neural-tube defects is reduced by as
much as 70% when women take folic acid as a dietary
supplement before and during the first trimester of
pregnancy.

67. Cont. One hypothesis is that more folate derivatives are
needed for the synthesis of DNA precursors when cell
division is frequent and substantial amounts of DNA
must be synthesized.

68. Treatment of Folate deficiency
Route of administration
Treatment
Intravenous
50 µg/day for 1 week
Oral
10 µg/day for 1 week
Harrison’s Principles of Internal Medicine; 16th Ed.; 2005; Pg. No

70. Anticancer Drug Targets
Thymidylate synthase and dihydrofolate reductase are
choice targets in cancer chemotherapy because the
generation of large quantities of precursors for DNA
synthesis is required for rapidly dividing cancer cells.

71. Thank you.