Folic acid

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FOLIC ACID

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

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FOLIC ACID

• 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.

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• 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

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• 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

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

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• 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

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• 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

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• 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

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• RDA
• 200 ug/day
• 400 ug/day for pregnancy Lactation
• Deficiency Manifestations
• dUMP not converted to TMP
• TMP not available for DNA synthease
• Cell division arrested
• cells rapidly dividing are affected
• Bone Marrow
• Intestinal cells

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• 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

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• Folate Antagonists
• Sulfonamides
• Analogs of PABA
• Bactericidal
• 2) Trimethoprim Folate reductase
• 3) Pyrimethamine
• Anti malarial drug
• 4) Aminopterin and Amethopterin
• Powerful inhibitors of Folate reductase

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VIT B12 COBALAMINorANTIPERNICIOUS ANEMIA FACTOR
orEXTRINSIC FACTOR OF CASTLE (EF)
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• Addison described Pernicions anemia.
• William Murphy George mint showed liver
  therapys effective.

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CHEMISTRY

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• 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

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• 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

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• Cyanocobalamin
• Hydroxycobalamin
• Ado B12 ------ Storage form
• Methyl cobalamin --- Major form seen in
  blood circulation

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SOURCES

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

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VITAMIN B12

• 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

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• 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

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• 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

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• 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

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• 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

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• Assay of B12
• Serum B12 is quantitated either by
  radioimmunoassay
• Schilling Test
• Methyl Malonic acid is excreted in urine
• FIGLU excretion test
• Peripheral blood and bone marrow morphology
• Achylia gastrica absence of acid in gastric
  juice
• Cystathionuria may be seen in vitamin B12
  deficiency

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