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

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.

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

 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 5 th or 10 th or 5 th & 10 th of ‘N’ atom of THFA

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

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 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

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

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

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 reductase 3) Pyrimethamine: ◦ Anti malarial drug 4) Aminopterin and Amethopterin: Powerful inhibitors of Folate reductase

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

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”

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

Cyanocobalamin Hydroxycobalamin Ado – B Storage form Methyl cobalamin --- Major form seen in blood circulation

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

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 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 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

 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 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

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