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