Biotin its role and deficiency disorder called burning feet syndrome folate trap and megaloblastic anemia

1. VITAMIN B7
BIOTIN

2. STRUCTURE
Heterocyclic
monocarboxylic acid.
Site of CO2 attachment

4. SOURCES
• Widely distributed.
Liver, kidney, milk and egg yolk.
Vegetables, legumes and grains.
Intestinal flora (A large percentage of biotin
requirement is supplied by intestinal bacteria).

5. • Coenzyme in carboxylation reactions.
Acetyl CoA carboxylase.
Propionyl CoA carboxylase.
Pyruvate carboxylase.
Methylcrotonyl CoA carboxylase.
• Role in regulation of cell cycle (biotinylate
nuclear proteins).
METABOLIC ROLE

6. DEFICIENCY
• Deficiency rare
Symptoms include dermatitis, glossitis, loss
of appetite and nausea.
Raw egg white contains a glycoprotein,
AVIDIN, which tightly binds biotin and
prevents its absorption from intestine.
(20eggs/day to induce deficiency)

7. VITAMIN B-9
FOLIC ACID

8. STRUCTURE
PTEROYL MONOGLUTAMIC ACID
Pteridine ring - PABA - glutamate
Chemically called pteroyl glutamic acid.

9. CHEMISTRY
In nature 3 forms are present.
1.Monoglutamate.
2.Triglutamate.
3. Heptaglutamate.

10. SOURCES
Widely distributed in animal and plant kingdom.
Liver
Beef
Kidney
Fish
Green leafy vegetables(foliage of plants)
Wheat
Beets, corn, broccoli.
Stored in liver, absorbed from duodenum(active n
passive transport)

11. RDA
ADULTS: 200 μg/d.
Children: 100-300 μg /d.
Pregnancy: + 100 μg/d.

12. ABSORPTION
Absorption occur in small intestine.
Diet polyglutamate monoglutamate(abs)
Tetrahydrofolate methyl-tetrahydrofolate
portal blood liver
Transported in blood as methyl tetrahydrofolate bound to specific protein.
BLOOD FOLATE LEVEL- 3-21 ng/ml
RBC FOLATE IS A RELIABLE INDICATOR OF FOLATE STATUS OF BODY.
(folate is incorporated in RBC during erythropoisis and retained during entire life.)
REDUCTASE
VIT C, NADPH+H

13. ACTIVE FORM
FH4 is active coenzyme form of folic acid.
It is obtained by addition of 4-H to pteridine moiety at
5,6,7 and 8 position.
They occur naturally in small amount.
1st
STEP
Folate H2-Folate(DHFA)
2nd
STEP
H2-Folate H4-Folate(THFA)
FA-REDUCTASE+ VIT
C
NADPH+H------NADP
DIHYDRO REDUCTASE+ VIT
C
NADPH+H--------- NADP
5,7 dihydrofolate
5,6,7,8 tetrahydrofolate

14. STRUCTURE OF
TETRAHYDROFOLATE
N N H
H2N H
N CH2 NH R
OH N H
H
Obtained by addition of 4 hydrogen to
pteridine moiety at 5,6,7,8 position.
8
7
6
5
10

16. ACTIVE FORM
5,6,7,8 THFA is inactive as such.
It give rise to several folic acid coenzyme which
act as carrier of various 1-C gp.
These 1-C gp can be attached to its molecules
in 3 ways:
 Attached to N no 5
 Attached to N no 10
 Attached to N no 5 & 10

17. 1-C- gp ATTACHED TO THFA
1-C-gp Attached to THFA Resulting compound
-CHO(FORMYL) N no 5 5-Formyl THFA
-CHO(FORMYL) N no 10 10-Formyl THFA
CH=NH(formimino) N no 5 5-Formimino THFA
-CH3(methyl) N no 5 5-Methyl THFA
CH2OH (hydroxy
-methyl)
N no 10 10-Hydroxymethyl THFA
-CH2-Methylene b/w N 5&10 5,10- Methylene THFA
=CH-Methenyl b/w N 5&10 5,10- Methenyl THFA

20. METABOLIC ROLE
DONOR GP
• Methyl gp of Methionine.
• Methyl gp of Betaine.
• Methyl gp of Thymine.
• β- C of Serine.
• Glycine, tryptophan,
acetone.
• -CH=NH gp of glutamate.
ACCEPTOR GP
• N- formyl methionine of T-
RNA.
• Glycine to form Serine.
• Homocysteine to form
Methionine.
• Uracil to form Thymine.
• Ethanolamine to form
Choline.
• Histidine synthesis.
• 2, 8C of purine ring.

21. Sources and utilization of 1-C
substituted folates
Sources of 1- C units Acceptor using 1-C unit
serine METHYLENE-THF serine
Glycine methyl-THF
Choline DNA methionine
Formimino - THF METHENYL-THF
Histidine
formyl-methionine
Formate FORMYL-THF purines
CO2

22. Metabolic Role
• The roles of folic acid
– 1) nucleic acid metabolism
– 2) amino acid metabolism

23. CAUSES OF DEFICIENCY
 Inadequate intake, unbalanced diet.
 Malabsorption- Celiac disease, Sprue, jejunum
resection
 Impaired Metabolism.
 Increased Requirement- Pregnancy ,Infancy
,Chronic Hemolytic Anemia ,Malignant Disease ,
Renal Dialysis.
 Folic acid Antagonist.
 Broad spectrum Antibiotics, Sulphonamides, anti
convulsant drugs( INHIBIT ENZYMES)

24. FOLIC ACID DEFICIENCY

26. DEFICIENCY MANIFESTATION
Deficiency seen in tissue cell with high mitosis
rate i.e. Hematopoietic System and Digestive
Tract.
Deficency Manifestations
1.Blood abnormalities 2. Growth retardations 3. Weakness
4. Lethargy 5. Inadequate lactation 6. Infertility.

27. FOLIC ACID ANTAGONIST

28. FA ANTAGONIST

29. FOLIC ACID ANTAGONISTS
Antagonists block conversion of DHFA to THFA.
On account of their inability to inhibit cell division and
multiplication they are used in treatment of condition
of unrestricted cell division.e.g
I. In Leukaemias.
II. In Erythraemias.
III. In malignant growths.

30. What are Neural Tube Defects?
Anencephaly Encephalocele

31. CLINICAL USES OF FOLIC ACID
1. Useful in treatment of certain macrocytic
anemias (Pregnancy, Infancy, Pellagra,
Gastric resection and alcoholism).
2. Used to lower plasma Homocysteine.

32. PERIPHERAL BLOOD PICTURE

33. LAB TEST FOR FOLIC ACID
DEFICIENCY
1. FIGLU TEST -HISTIDINE LOAD TEST.
N-Formimino-glutamate excreted in urine
FH4
N5 formyl FH4 TCA cycle
Glutamate
formimino
transferase
Folic acid deficiency

35. LAB TEST FOR FOLIC ACID
DEFICIENCY
2. Histidine loading Test.
3. Serum Folic Acid.
4. Erythrocyte Folic Acid.
R.B CELL FOLATE
• Folate is incorporated in RBC during erythropoiesis
and is retained there during their entire life span.
• RBC folate is reliable indicator of folate status of body.

36. RISK OF EXCESS FOLIC ACID
Irreversible nerve damage.
Renal Damage.

37. THANK YOU.