RIBOFLAVIN (B2)

RIBOFLAVIN (B2)

1. Riboflavin (B2] Gandham . Rajeev Department of Biochemistry, Akash Institute of Medical Sciences & Research Centre, Devanahalli , Bangalore, Karnataka, India. E-Mail: [email protected]

2. Structure Riboflavin is a yellow pigment Riboflavin contains 6,7 – dimethyl isoalloxazine ring attached to D- ribitol by a nitrogen atom Ribitol is an open chain form of sugar ribose with aldehyde group is reduced to alcohol It emits yellow fluorescence It is stable to heat but sensitive to light

3. When exposed to UV rays of sun light, it is converted to lumiflavin which exhibits yellow fluorescence Lactoflavin from milk Hepatoflavin from liver Ovoflavin from eggs are structurally identical to riboflavin

4. Structure of Riboflavin N NH O O N N H 3 C H 3 C I H - C - OH I H 3 C I H - C - OH I H - C - OH I CH 2 OH RIBITOL Riboflavin ATP ADP Flavokinase Isoalloxine ring

5. N NH O O N N H 3 C H 3 C I H - C - OH I H 3 C I H - C - OH I H - C – OH I CH 2 O - P – O - FMN ATP PPi FAD synthase O O

6. N NH O O N N H 3 C H 3 C I H - C - OH I H 3 C I H - C - OH I H - C – OH I CH 2 O - P – O FAD O O - P – O O O -CH 2 H N N NH 2 I N N H

7. Absorption: Riboflavin is present in the food as FAD, FMN and free riboflavin FMN & FAD are hydrolysed to free form in upper small intestine Free form is absorbed by intestinal mucosal cells by sodium dependent transport system Transport: In the intestinal mucosal cells riboflavin is converted into FMN by the action of flavokinase in the presence of ATP

8. FMN enters the portal circulation In the plasma it is transported as Albumin-FMN complex FMN complex enters the tissues including liver In the tissues it is converted into FAD Storage: Riboflavin is mainly stored in liver It is stored as FMN & FAD Excretion: Mainly excreted in urine

9. Coenzymes of Riboflavin: FMN & FAD The Ribitol is linked to phosphate in FMN FAD is formed from FMN by transfer of an AMP from ATP Biochemical functions: FAD & FMN participate in many redox reactions responsible for energy production The functional unit is isoalloxazine ring, serves as an acceptor of two hydrogen atoms

10. FMN or FAD undergo identical reversible reactions accepting 2H atoms forming FMNH 2 or FADH 2 Flavoproteins: The enzymes that use flavin coenzymes are called as flavoproteins Metalloflavoproteins: Many flavoproteins contain metal atoms (iron, molybdenum etc) which are known as metalloflavoproteins

11. L – Amino acid oxidase : It catalyzes the conversion of L-amino acid to the α - ketoacid Ammonia is released & FMN is reduced to FMNH 2 L-Amino acid + FMN α - Keto acid + NH 3 + FMNH 2 L – amino acid oxidase Reactions requiring FMN

12. Reactions requiring FAD Carbohydrate metabolism: PDH Complex: PDH complex catalyzes the oxidative decarboxylation of pyruvate to acetyl CoA NAD is reduced to NADH + H + FAD is present in Dihydrolipoyl dehydrogenase of PDH Pyruvate Acetyl CoA PDH Complex FAD FAD FADH2

13. α - Ketoglutarate dehydrogenase complex: It catalyzes the oxidative decarboxylation of α - Ketoglutarate to succinyl CoA FAD is present in dihydrolipoyl dehydrogenase of α - Ketoglutarate dehydrogenase complex α - Ketoglutarate Succinyl CoA α - KetoglutarateComplex FAD FAD FADH2 CoA SH CO 2

14. Succinate dehydrogenase: It catalyzes the oxidation of succinate to fumarate FAD is reduced to FADH 2 Succinate FAD Fumarate Succinate Dehydrogenase FADH 2

15. Lipid Metabolism Acyl CoA Dehydrogenase : It catalyses the Oxidation of fatty acyl CoA to 2, 3 unsaturated acyl CoA Fatty acyl CoA 2, 3 unsaturated acyl CoA Acyl CoA dehydrogenase FAD FADH 2

16. Mitochondrial Glycerol 3-P dehydrogenase It catalyzes the conversion of glycerol 3P to DHAP in mitochondria It essential for carrying reducing equivalents from cytosol to mitochondria Glycerol 3-phosphate DHAP Mitochondrial glycerol 3-P dehydrogenase FAD FADH 2

17. Protein metabolism Glycine cleavage system: It catalyzes the conversion of glycine to CO 2 and ammonia FH 4 is converted into N 5,10 methylene FH 4 Glycine + FH4 N 5,10 methylene FH 4 + CO 2 + NH 3 Glycine cleavage system

18. D – Amino acid Oxidase It catalyzes the conversion of D – amino acids or glycine to corresponding ketoacids Ammonia is reduced FAD is reduced to FADH 2 D – Amino acid + FAD α - Keto acid + NH 3 + FADH 2 D – Amino acid Oxidase

19. Purine metabolism Xanthine Oxidase: It catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid Xanthine oxidase contains FAD, molybdenum and iron Hypoxanthine Xanthine Xanthine oxidase FAD FADH 2 Uric acid Xanthine oxidase

20. Dietary sources Rich sources are milk, milk products, meat, eggs, liver and kidney Moderate sources are cereals, fruits, vegetables and fish RDA: Men - 1.5 mg/day Women - 1.2 mg/day Pregnancy & lactation - 1.5 mg/day

21. + Deficiency Causes: Inadequate intake Impaired absorption due to intestinal diseases Chronic alcoholics are susceptible to B 2 deficiency Clinical features: Cheilosis ( fissures at the corners of mouth ) Glossitis ( tongue smooth and purplish ) Dermatitis

22. Corneal vasculalarization : includes dryness, burning & itching and lacrimination Measurement of glutathione reductase in erythrocytes is a reliable diagnostic test to assess riboflavin deficiency Reference interval Serum or plasma level is 4 to 24 µg/ dl

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