vitamin B1, B2, B3 by biochemistry - Online.pptx

All the details including in vitamin B complex

1. Vitamin B complex Dr. Amit D. Sonagra . Associate Professor, Department of Biochemistry. [email protected]

2. Vitamin B - headings Chemistry & different forms Functions of all forms. Sources & RDA. Deficiency: causes, signs & symptoms, diagnosis, tests & treatment. Other aspects: Antivitamins , vitamin as treatment.

3. Vitamin B1- Thiamine Thiamine = Vitamin B1 Thymine = Nitrogen base of DNA

4. Vitmain B1 ( Thiamine ) Also k/a Aneurine (as it can relieve neuritis) or antiberiberi factor . Chemically it is Pyrimidine ring attached to thiazole attached with methelene bridge. Active co-enzyme form  Thiamine pyrophosphate (TPP)

5. Conversion to active form Major biological active form is Thiamine Pyro Phosphate. Thiamine. ATP TPP Transferase . AMP Thiamine Pyro Phosphate.

6. Functions of thiamine Coenzyme in Oxidative decarboxylation of alpha ketoacids .

7. e.g. Pyruvate Dehydrogenase complex

8. Other examples… Alpha ketoglutarate DH complex: Alpha ketoglutarate  Succinyl CoA . Alpha keto acid dehydrogenase of branched chain amino acid metabolism.

9. TPP as coenzyme in transketolase TPP

10. HMP Shunt Pathway

11. Sources of Vitamin B1 Outer ( Aleurone ) layer of cereals is rich in Vit B1. Whole wheat floor & unpolished hand pound rice have better nutritive value. While white floor (Maida) & Polished rice have low Vit B1 content. Yeast, Milk, egg are also good sources of Vit B1. RDA: 0.5mg/1000 Cal or 1-1.5mg/day.

12. Aleurone layer in wheat and rice

13. Thiamine deficiency Causes: Dietary deficiency of vit B1. Alcoholism: Because alcohol increases metabolic demand of Thiamine & also reduces absorption at intestine. Malabsorption syndrome Clinical features: Anorexia, weakness, irritable mood, abdominal discomfort etc. are earlier symptoms. If left untreated  Disease progresses.

14. Beri beri Beri beri  Means Weakness. 3 types: Wet beri beri : Cardiovascular manifestations Dry beri beri : Neurological manifestations Infantile beri beri : seen in infants of mothers suffering from Vit B1 deficiency.

15. Wet beri beri Substantial cardiac involvement in addition to peripheral neuropathy. Characterized by : Tachycardia, Palpitation, Dyspnea . Pre cordial pain. Cardiomegaly . Distended neck veins. Dependent edema. Oliguria , Death.

16. Dry beri beri Usually seen in older adults & affects mainly peripheral nerves with little cardiac involvement. Characterized by : Sensory disturbances. Pain & tenderness of Calf muscle. Difficulty in rising from squatting position. Wrist drop Foot drop Wasting of muscle. Loss of Deep tendon reflexes.

17. Infantile beri beri Usually seen in breast fed infants between second & fifth months of life whose mother is Thiamine deficient. Characterized by : Anorexia, Restlessness, Sleeplessness. Vomiting, Abdominal pain, Loss of reflexes. Convulsion, Coma, Death. Sign & symptoms are mainly because of Acute Cardiac Failure

18. Wernicke Korsakoff syndrome Also k/a Cerebral Beri Beri . Thiamine deficient disease, mainly affects alcoholics as of three reason. Diet intake is usually poor. Alcohol utilization needs large amount of thiamine. Alcohol inhibits intestinal absorption of thiamine. Wernicke – Korsakoff syndrome is actually two disorders in one.

19. Wernicke’s disease Manifestation of Acute Thiamine deficiency occur following a few days of binge drinking. Involves damage to nerves in CNS & PNS. Characterized by : Global confusion: Most common mental symptom. Opthalmoplagia : Ptosis , Diplopia . Ataxia

20. Korsakoff Psychosis Manifestation of chronic Thiamine deficiency. Characterized by: Impairment of recent memory . Retrograde amnesia: Failure to remember events immediately before illness Impaired ability to learn. Confabulation: Production of fictitious details to fill gaps in memory. Psychosis.

21. The mortality of Wernike – Korsakoff syndrome is 90% without therapy. Most common cause of death being sudden heart failure. Early treatment may result complete recovery. However some findings may persists like loss of memory or confabulation.

22. Why these symptoms occur in Vit B1 deficiency..?? Difficulty in cellular breakdown of Carbohydrate to form ATP – a fuel source used for cell growth, function and repair. Pyruvic acid builds up in blood stream, causing a loss of mental alertness , difficulty in breathing & heart damage. Neurological symptoms - due to Degeneration of Nerve fibers & their Demylination .

23. Diagnosis of vit B1 deficiency Based on clinical features. Diagnostic tests: Erythrocyte Transketolase Activity : earliest for diagnosis. Blood Thiamine level. Blood Pyruvate , Lactate, Alpha Keto glutarate level.

24. Treatment Supplementation of Thiamine through diet or drug. Thiamine has also some role in therapy of: Alzheimer's disease. Epilepsy. Fibromyalgia. Alcoholic polyneuropathy . Neuritis of Pregnancy. Neuritis of Old age.

25. Vitamin B2- Riboflavin

26. Vitamin B2  Riboflavin Chemically: Isoalloxazine + Ribitol . Active forms: FMN: Flavin Mononucleotide FAD: Flavin Adenine Dinucleotide .

27. FMN Dependant Enzymes Acts as Hydrogen Acceptor / Donor. L-Amino acid oxidase : L-Amino acid + FMN  L- Keto acid + FMNH 2 + NH 3 Complex I of electron transport chain.

28. FAD Dependant enzymes Complex II of electron transport chain. TCA Cycle: Succinate Dehydrogenase : Succinate  Fumarate . β Oxidation: Acyl CoA DH: Acyl CoA  α , β - Enoyl CoA . Xanthine Oxidase : Xanthine  Uric acid. Pyruvate DH complex: Pyruvate  Acetyl CoA . α ketoglutarate DH complex: α - Ketoglutarate  Succinyl CoA .

29. Sources & RDA Sources: Rich sources: Liver, Egg, Whole milk, Yeast Good sources: Fish, Cereals, Legumes, Green leafy vegetables RDA: 1.5 mg/day

30. Riboflavin deficiency Causes: Nutritional deficiency is relatively uncommon. But seen in patients with Alcoholism, Malabsorption syndrome. Prolonged use of antibiotics  Intestinal flora also synthesize some amount of Riboflavin.

31. Clinical features: Sore throat, Redness and swelling of the lining of the mouth and throat. Angular Stomatitis : Inflammation of angle of mouth Cheilosis : Cracked Lips Glossitis : Inflammation of tongue  Magenta Tongue. Circum Corneal vascularization . Seborrheic dermatitis: Dandruff on scalp.

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33. Diagnosis: Mainly based on signs & symptoms. No specific diagnostic test available. Treatment: Supplementation of Riboflavin through diet or drug.

34. Vitamin B3- Niacin Nicotinic acid = Niacin ( Vit B3) Nicotine = Potent poison of Tobacco

35. Vitamin B3 = Niacin = Nicotinic acid Also k/a Pellagra preventing factor of Goldberger. Chemically: Pyridine-3-Carboxylic acid. Active forms: NAD + /NADH, NADP +/ NADPH

36. In NADP +  phosphoric acid residue is attached to the hydroxyl group marked with asterisk

37. Functions of NAD & NADP: NAD + /NADH & NADP +/ NADPH acts as Acceptor or Donor of Hydrogen molecule in various reactions. 2H  H + e - + H +  H - (Hydride ion) + H + NAD + + Lactate  NADH + H + + Pyruvate NADH  Electron transport chain  2.5 ATP NADPH  Biosynthesis of FA, cholesterol & Free radical scavenging mechanisms.

38. Enzymes using NAD + /NADH: Lactate Dehydrogenase ( Pyruvate  Lactate) Glyceraldehyde 3 Phosphate DH (Gly3P  Gly1,3 BP) Pyruvate DH ( Pyruvate  Acetyl CoA ) Alpha ketoglutarate DH ( α -KG  Succinyl CoA ) Glutamate DH (Glutamate  α -KG)

39. Enzymes generating NADPH: Glucose 6 Phosphate DH of HMP shunt pathway 6 Phosphogluconolactone DH of HMP shunt pathway Malic enzyme ( Malate + NADP +  Pyruvate + CO 2 + NADPH + H + ) Cytoplasmic Isocitrate DH

40. NADPH utilizing reactions: Fatty acid synthesis Keto acyl DH ( β Keto Acyl enzyme  β OH Acyl -E) Enoyl reductase ( α , β unsaturated Acyl -E  Acyl -E) Cholesterol synthesis HMG CoA reductase (HMG CoA  Mevalonate ) Met-Hemoglobin  Hb Folate reductase ( Folate  DHF  THF) Phenyl alanine hydroxylase ( Phe  Tyr) Keep glutathione in reduced state  relieve oxidative stress To generate free radicals in Macrophage for killing.

41. Sources & RDA Sources: Yeast, liver, legumes, fish & meats Limited amount of niacin obtained from tryptophan 60 mg tryptophan ~ 1 mg Niacin generated RDA: 20mg/day.

42. Niacin deficiency - Pellagra Pellagra (Italian word) = Rough skin Pellagra is seen more commonly in women because tryptophan metabolism is inhibited by estrogen metabolite. Clinical features: 3D Dermatitis: Diarrhoea : Dementia:

43. Dermatitis: Initially bright red erythema on feet, ankle, face Later on, Increased pigmentation of sun exposed areas. Casal’s necklace  Pigmentation around neck. Diarrhoea : Nausea, vomiting may also be present. Dementia: Irritability, inability to concentrate, poor memory.

44. Causes: Dietary deficiency of Tryptophan: Seen with typical staple diet. Maize: Niacin is in bound form , so unavailable. Jowar : Contains Leucine in high quantity which inhibits QPRT ( Quinolinate Phosphoribosyl Transferase ) enzyme, so Niacin  NAD conversion do not occur. Deficient synthesis of NAD: Kynureninase , enzyme in pathway of Trp  NAD. PLP - Pyridoxal Phosphate is cofactor required. Vit B6 deficiency  indirect deficiency of Niacin.

45. Drugs (INH- Isoniazide ): Inhibits pyridoxal phosphate-PLP formation. Hartnup disease: Tryptophan absorption at intestine & reabsorption at renal tubule is defective  NAD deficiency. Carcinoid syndrome: These tumors uses major portion of Tryptophan for synthesis of serotonin, so less Trp is available for synthesis of NAD.

46. Diagnosis: Mainly based on signs & symptoms. Treatment: Change of staple diet. Vitamin supplements as diet & drugs.

47. Niacin (Nicotinic acid) as drug: Niacin (Nicotinic acid) reduces lipolysis at adipose tissue β-oxidation & generation of Acetyl CoA is reduced Cholesterol synthesis is reduced Reduction of serum cholesterol.

48. Niacin toxicity Excess of Niacin when given orally or parenterally , produces transient vasodilatation of cutaneous vessels & Histamine release. Burning & itching of skin. Niacin >50mg/day can cause liver damage.

49. Summary Thiamine: Active form: TPP; Coenzyme in α - keto acid DH & Transketolase Deficiency: Beri beri , Wernicke-Korsakoff syndrome. Riboflavin: Active forms: FMN, FAD Coenzyme in ETC & various enzyme reactions. Deficiency: Cheilosis , Glossitis , Angular stomatitis Niacin: Active forms: NAD, NADP Coenzyme in ETC & various enzyme reactions. Deficiency: Pellagra

50. Important questions Vitamin B1/ Thiamine (3 or 5 marks, viva) Vitamin B1 deficiency (2 or 3 marks, viva) Beri beri (2 marks, viva) Wernicke Korsakoff syndrome (2 marks, viva) Why unpolished hand pound rice are beneficial? (2 marks, viva) Riboflavin (2 marks) Riboflavin deficiency (viva, spotting) Niacin (3 or 5 marks) Pellagra (viva, case)