THIAMINE (B1)

THIAMINE (B1)

1. Thiamine (B1] Gandham . Rajeev Department of Biochemistry, Akash Institute of Medical Sciences & Research Centre, Devanahalli , Bangalore, Karnataka, India. E-Mail: [email protected]

2. Thiamine B 1 Thiamine ( anti- beri - beri or antineuritic vitamin ) is water soluble vitamin It has a specific coenzyme, thiamine pyrophosphate (TPP) Chemistry: Thiamine contains pyrimidine ring and a thiazole ring held by a methylene bridge

3. The alcohol group of thiamine is esterfied with phosphate (2 moles) to form the coenzyme, thiamine pyrophosphate (TPP or Cocarboxylase ) The phosphate moiety is donated by ATP & reaction is catalyzed by thiamine pyrophosphate transferase Thiamine is a sulphur containing water soluble vitamin

4. N N NH2 H 3 C CH 2 S N -CH 2 - CH 2 – O - P- O – P - O O O O O Pyrimidine ring Methylene bridge Thiazole Pyrophosphate CH 3 Structure of TPP

5. Metabolism: Absorption: Thiamin is carried by the portal blood to the liver, present as free thiamine Storage: stored as thiamin pyrophosphate Mainly stored in skeletal muscle and also present in significant amounts in liver, heart, kidneys, erythrocytes and nervous system Coenzyme form: TPP

6. Bio chemical functions The coenzyme, TPP or Cocarboxylase is connected with energy releasing reactions in the carbohydrate metabolism Pyruvate dehydrogenase complex: It catalyses the irreversible conversion of pyruvate to acetyl CoA It is essential for complete oxidation of glucose It links glycolysis and TCA cycle

7. Transketolase is dependent on TPP It is involved in HMP shunt Pyruvate Acetyl CoA PDH Complex NAD+ NADH + H+ TPP

8. α - Ketoglutarate dehydrogenase complex : It converts α - Ketoglutarate succinyl CoA in TCA cycle α - Ketoglutarate Succinyl CoA α - Ketoglutarate DH Complex NAD+ NADH + H+ TPP

9. The branched chain α - Keto acid dehydrogenase ( decarboxylase ): It catalyses the conversion of α - keto acids to corresponding acyl CoA Essential for transmission of nerve impulse TPP is required for synthesis of Acetylcholine Branched chain α - Keto acid Corresponding Acyl CoA NAD+ NADH + H+ TPP Branched chain α - Keto acid DH Complex

10. Glucose Glucose – 6 P Pyruvate Acetyl CoA TPP PDH TCA TPP Citrate Oxaloacetate α - Ketoglutarate α - Ketoglutarate dehydrogenase Succinyl CoA Ribose - 5P Transketolase TPP Seduheptulose - 7P Xylulose - 5P Glyceraldehyde - 3P

11. Dietary sources Rich sources of thiamine are unrefined cereal grains (rice, wheat), legumes (beans) Animal sources are liver, kidney, milk Thiamine is mostly concentrated in outer layer of cereals Polishing of rice removes 80% of thiamine Thiamine is water soluble, and is excreted into water during cooking process

12. RDA Adults - 1-1.5 mg/day Children - 0.7-1.2 mg/day Pregnancy & lactation - 2 mg/day Deficiency : Causes: B1 deficiency is caused by inadequate intake of thiamine in diet

13. Eating fishes containing microbial thiaminase , it hydrolytically destroys thiamin Impaired absorption is caused by intestinal diaorders Increased requirement of thiamine is seen in hyperthyroidism, fever, pregnancy and lactation Chronic alcoholism is common cause of B1 deficiency

14. Biochemical changes in B1 deficiency Carbohydrate metabolism is impaired Accumulation of pyruvate in tissues Excretion of pyruvate in urine Normally, pyruvate does not cross the blood-brain barrier (BBB) In thiamine deficiency alteration occurs in BBB and permits pyruvate into brain It results in disturbed metabolism, it may be responsible for polyneuritis

15. B1 deficiency leads to impairment in nerve impulse transmission due to lack of TPP Transketolase activity in erythrocytes is decreased Measurement of RBC transketolase activity is reliable diagnostic test to assess B1 deficiency

16. + Clinical features Thiamine deficiency causes a clinical condition called Beri-Beri Commonly seen in populations consuming exclusively polished rice as staple food Clinical features of thiamine deficiency are grouped into Wet beri - beri : It is characterized by edema of legs, face, trunk & serous cavities

17. Systolic BP is elevated & diastolic BP is decreased Tachycardia Fast & bouncing pulse is observed Enlargement of heart Heart becomes weak & death may occur due to heart failure

18. Dry beri-beri : Associated with neurological manifestations Clinical features Peripheral neuritis with numbness Tingling sensations in the lower legs & feet Ataxic gait Loss of weight Muscles become weak & walking becomes difficult Mental confusion

19. Cerebral beri-beri Called as Wernicke-Korsakoff syndrome Mostly seen in chronic alcoholics Insufficient intake or impaired absorption of thiamine Loss of memory, Apathy Rhythmical to & fro motion of eye balls

20. Infantile beri-beri Seen in infants born to mothers suffering from thiamine deficiency The breast milk of these mothers contain low levels of thiamine It usually occurs during 2-4 months Clinical features include Sleeplessness Restlessness Vomiting, convulsions Death may occur due to cardiac failure

21. Biochemical findings Increased plasma levels of pyruvate & lactate due to low activity of PDH complex Accumilation of pentose sugars in erythrocytes is due to decreased activity of transketolase Measurement of Transketolase activity is common test used for the diagnosis of B1 deficiency

22. Antimetabolites Thiaminase It is present in raw fish & seafood Thiaminase destroys thiamine if it is present in the diet

23. References Harper’s Biochemistry 25 th Edition. Fundamentals of Clinical Chemistry by Tietz . Text Book of Medical Biochemistry-A R Aroor . Text Book of Biochemistry-DM Vasudevan Text Book of Biochemistry-MN Chatterjea Text Book of Biochemistry- Dr.U.Satyanarana