This document discusses folic acid and vitamin B12. It describes: 1) Folic acid is present in vegetables and consists of three parts. It is involved in DNA synthesis and preventing cancer and heart disease. 2) Deficiencies can result from pregnancy, malabsorption, drugs that inhibit enzyme activity, and lack of vegetables in the diet. This leads to megaloblastic anemia. 3) Vitamin B12 contains cobalt and is only found in animal products. Deficiencies can result from gastric issues or lack of intrinsic factor leading to neurological problems like subacute combined degeneration of the spinal cord.

1. M.Prasad Naidu
MSc Medical Biochemistry,
Ph.D.Research Scholar

2. Folium – leaf of vegetables
Abundant in Vegetables
Chemistry:-
Consist of three parts
–Pteridine ring
–GABA
–Glutamic acid
Photosensitivity
In nature present as polyglutamate. 5-7 glutamates are
attached to Pteroyl group.

3. Folacin – name given to compounds containing folic
acid
Ab – Ab in monoglutamate form. Ab in Jejunum
Transported to liver and co – enzyme is formed
tetrahydrofalate
THFA formation:
I step:- 7,8 – dihydrofolic acid is formed
II step:- 5,6,7,8 tetrahydrofolic acid id formed
catalysed by NADPH dependent folate Reductase

4.  THFA is the carrier of one carbon groups
 One carbon compounds are organic molecules that
contain only single carbon atom
 One ‘C’ is attached to 5th
or 10th
or 5th
& 10th
of ‘N’ atom
of THFA

5. General Function of Folic Acid:
 Benificial in preventing Cancer
1. HPV:-
cancer cervix – 1/5 reduced if folic acid is given
2. Reduced Homocysteine levels and prevents CAD
3. Folic acid deficiency leads to Renal tubular defects

6. Cause for folate deficiency:
 Pregnancy – requirement more
 Defective absorption
◦ Sprue
◦ Celiac
◦ Gluten induced enteropathy
◦ Resection of Jejunum
◦ Gastroileostomy
 Poly glutamates in diet
Ab only mono glutamate
Enzymes cleave poly glutamates to mono
glutamates

7. But drugs like inhibit these enzymes
Hydantoin
Dilantin
Phenytoin
Phenobarbitone
No Ab in these patients
4. Haemolytic anemias
5. Absence veg., in diet
For prolonged periods – deficiency
 G.I.T:- Vomitings
Pain Abdomen
Diarrhoea

8. Assay:
Normal serum FA levels: 20 nanogram/ml
200 ug/packed cell ml
RIA measurement:
Histidine load test:-
15gr Histidine
Urine collected 24hrs-
Normal 35 mg/FIGLUE is excreted
But in FA deficiency more is excreted
Peripheral Blood Pressure
Macrocytic Anemia

9. RDA:
200 ug/day
400 ug/day for pregnancy & Lactation
Deficiency Manifestations:
1) dUMP not converted to TMP
TMP not available for DNA synthease
Cell division arrested
cells rapidly dividing are affected
 Bone Marrow
 Intestinal cells

10. 2) Macrocytic Anemia:
 Most characteristic feature of Folic acid deficiency
 Mature Oesinophylic cytoplasm
 Immature nucleus
 Reduced production
 Increased Haemolysis
 Leads to anemia in FA deficiency
 Leukopenia
 thrombocytopaenia

11. Folate Antagonists:
1) Sulfonamides
◦ Analogs of PABA
◦ Bactericidal
2) Trimethoprim – Folate reductase
3) Pyrimethamine:
◦ Anti malarial drug
4) Aminopterin and Amethopterin:
Powerful inhibitors of Folate reductase

16. Addison described Pernicions anemia.
William Murphy & George mint showed liver therapy’s
effective.

19. Water soluble
Heat stable
Red in color
Contains 4.35% cobalt by weigh
It contains C63 14 N one cobalt four pyrole rings co-
ordinated with a cobalt atom is called “Corrin ring”

20. There is similarity between corrin ring and prophyrin ring
and 5th
valency of cobalt is covalently linked to a
substituted benzimidazole ring.
Then the ring is called cobalamin
The 6th
valency of the cobalt is by cyanide, Hydroxyl,
Adenosyl & Methyl

21. Cyanocobalamin
Hydroxycobalamin
Ado – B12 ------ Storage form
Methyl cobalamin --- Major form seen in
blood circulation

23. Animal origin only
Liver
Egg
Curds – Vegetarian
Meat
Fish
Lactobacillus can synthesize

24. RDA 1-2micro gm/day
Those who take Folic acid should take B12
Elderly -------supplementation B12
Absorption requires IF,ileum
Gastric Parietal cells
glycoprotein
Mol wt 50,000
IF---------- 2 molecules B12

26.  B12& IF complex is formed
 IF is digested in the mucosal cells
 B12 carried through Transcobalamin II
 Stored in LIVER as Ado-B12 form in combination with
Transcobalamin I or Transcorrin
 Methyl cobalamin

28. Abnormal Homocysteine level if
Methyl cobalamin
 Demylination – Neurological deficiency
 Sub – acute combined degeneration of the cord.A
unique manifestation of B12
 Mistaken for Diabetic Neuropathy or Neuropsychiatric
disorders
 Lateral and posterior colums of the cord are affected
 There is sensory and motor neuron disturbances
seen

29.  Cortico – spinal tracts – Hyperactive tendon reflexes
 Posterior column affected - Loss of position and
vibratory sensations seen
 Both motor and sensory systems are affected – Sub
acute combined degeneration of cord
 Defect may be due to defective formation of SAM

33. Causes Of B12 Defficiency:
 Common in India especially in vegetarian
 Decreased absorption
1. Gastrectomy
2. Resection of Ileum
3. Blind loop syndrome
4. Malabsorption syndrome
5. Elderly people
6. Addisonian Pernicious Anemia -
antibodies against intrinsic factor
7. Iron deficiency Anemia - Gastric Atropy -
decreased production of intrinsic factor

34. Assay of B12:
1) Serum B12 is quantitated either by
radioimmunoassay
2) Schilling Test
3) Methyl Malonic acid is excreted in urine
4) FIGLU excretion test
5) Peripheral blood and bone marrow morphology
6) Achylia gastrica – absence of acid in gastric juice
7) Cystathionuria may be seen in vitamin B12
deficiency