M.Prasad NaiduMSc Medical Biochemistry,
Ph.D.Research Scholar
Folium – leaf of vegetablesAbundant in VegetablesChemistry:-Consist of three parts
–Pteridine ring –GABA–Glutamic acidPhotosensitivityIn nature present as polyglutamate. 5-7 glutamates are attached to Pteroyl group.
Folacin – name given to compounds containing folic acid
Ab – Ab in monoglutamate form. Ab in JejunumTransported to liver and co – enzyme is
formed tetrahydrofalateTHFA formation:I step:- 7,8 – dihydrofolic acid is formedII step:- 5,6,7,8 tetrahydrofolic acid id formed
catalysed by NADPH dependent folate Reductase
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
General Function of Folic Acid: Benificial in preventing Cancer1. 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
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
But drugs like inhibit these enzymesHydantoinDilantinPhenytoinPhenobarbitone
No Ab in these patients4. Haemolytic anemias5. Absence veg., in diet
For prolonged periods – deficiency G.I.T:- Vomitings
Pain AbdomenDiarrhoea
Assay:Normal serum FA levels: 20 nanogram/ml 200 ug/packed cell
mlRIA measurement:Histidine load test:-
15gr HistidineUrine collected 24hrs-Normal 35 mg/FIGLUE is excretedBut in FA deficiency more is excretedPeripheral Blood PressureMacrocytic Anemia
RDA:200 ug/day400 ug/day for pregnancy & Lactation
Deficiency Manifestations:1) dUMP not converted to TMP
TMP not available for DNA syntheaseCell division arrestedcells rapidly dividing are affected
Bone Marrow Intestinal cells
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
Folate Antagonists:1) Sulfonamides
◦ Analogs of PABA◦ Bactericidal
2) Trimethoprim – Folate reductase3) Pyrimethamine:
◦ Anti malarial drug4) Aminopterin and Amethopterin:
Powerful inhibitors of Folate reductase
Addison described Pernicions anemia.William Murphy & George mint showed liver
therapy’s effective.
Water solubleHeat stableRed in colorContains 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”
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 cobalaminThe 6th valency of the cobalt is by cyanide, Hydroxyl, Adenosyl & Methyl
Cyanocobalamin Hydroxycobalamin
Ado – B12 ------ Storage form
Methyl cobalamin --- Major form seen in blood circulation
Animal origin onlyLiverEggCurds – VegetarianMeatFishLactobacillus can synthesize
RDA 1-2micro gm/dayThose who take Folic acid should take B12Elderly -------supplementation B12Absorption requires IF,ileum Gastric Parietal cells glycoprotein Mol wt 50,000IF---------- 2 molecules B12
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
Abnormal Homocysteine level ifMethyl 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
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
Causes Of B12 Defficiency: Common in India especially in vegetarian Decreased absorption
1. Gastrectomy 2. Resection of Ileum 3. Blind loop syndrome4. Malabsorption syndrome 5. Elderly people6. Addisonian Pernicious Anemia - antibodies against intrinsic factor 7. Iron deficiency Anemia -
Gastric Atropy - decreased production of intrinsic factor
Assay of B12:1) Serum B12 is quantitated either by
radioimmunoassay2) Schilling Test3) Methyl Malonic acid is excreted in urine4) FIGLU excretion test5) Peripheral blood and bone marrow
morphology6) Achylia gastrica – absence of acid in gastric
juice7) Cystathionuria may be seen in vitamin B12
deficiency
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