Pantothenic acid(B5)

Metabolism of Panthotenic Acid (B5)

1. Panthothenic acid (B5] Gandham . Rajeev Department of Biochemistry, Akash Institute of Medical Sciences & Research Centre, Devanahalli , Bangalore, Karnataka, India. E-Mail: [email protected]

2. PANTOTHENIC ACID (B5)

3. Pantos means ‘ everywhere ’ It is widely distributed in nature It is formerly known as chick anti-dermatitis factor Its metabolic role as a coenzyme A (Discovered by Lipmann) Chemistry: Pantothenic acid is composed of pantoic acid joined to β – alanine by a peptide bond It is stable to heat & destroyed by acid & alkali

4. Absorption: It is present in food either free form or coenzyme form Coenzyme form is hydrolyzed to free form by intestinal pyrophosphatase Free pantothenic acid is absorbed from upper part of small intestine by sodium dependent transport system Transport it enters portal circulation & transported to various tissues Metabolism

5. Coenzyme A & Form Coenzyme A & 4-phosphopantetheine Pantothenic acid is first phosphorylated to form 4-phospho pantothenic acid 4-phosphopantothenic acid is converted into 4-phosphopantothenylcysteine by the transfer of cysteine molecule to 4-phosphopantothenic acid 4-phosphopantothenylcysteine is decarboxylated to form 4-phosphopantetheine

6. 4-phosphopantetheine is converted to dephospho coenzyme A by transfer of AMP Dephospho coenzyme A phosphorylated to form CoA

7. OH - CH 2 – C – CH – C – NH - CH 2 - CH 2 – COO - CH 3 I O II I CH 3 OH I Pantoic acid β - Alanine Pantothenic acid 4-phospho pantothenate 4-phosphopantothenyl cysteine Cysteine ATP ADP ATP ADP 4-phosphopantotheine Dephospho -coenzyme A Coenzyme A ATP PPi

8. CH 2 – C – CH – C – NH - CH 2 - CH 2 – CO -N-CH 2 - CH 2 - SH CH 3 I O II I CH 3 OH I I OIP I O IP O - O - =O - O - = O – CH2 H N N N N NH 2 I OH H H H - O - =O O I P I O - Ribose - 3 P Adenine H I Coenzyme A

9. Role of 4-phosphopantetheine 4-phosphopantetheine is required for De novo synthesis of FA 4-phosphopantetheine is a carrier of acyl groups 4-phosphopantetheine is attached to ACP of FAS complex 4-phosphopantetheine contributes to peripheral SH group of FAS complex Acyl groups are attached to SH groups of FAS

10. The functions of pantothenic acid are exerted through coenzyme A or CoA (A for acetylation) Co A is involved in all the metabolisms It plays a role in integrating various metabolic pathways Coenzyme A has a terminal thiol or sulfhydryl group (-SH) SH group is the reactive site Hence CoA-SH is used Biochemical functions

11. Acyl groups are linked to coenzyme A by thioester bond, to give acyl CoA CoA serves as a carrier of activated acetyl or acyl groups Enzymes requiring Coenzyme A as cofactor: Pyruvate dehydrogenase complex α - Ketoglutarate dehydrogenase complex FAS complex Thiolase, HMG CoA synthase

12. Acetyl Co A is formed from oxidation of pyruvate to , amino acids, FA, ketone bodies Utilization: Acetyl CoA is utilized for oxidation through TCA cycle to provide energy It essential for formation of Acetylcholine Acetylcholine is neurotransmitter Acetyl CoA is the substrate for synthesis of FA, cholesterol, Amino acids, & ketone bodies Role of acetyl CoA

13. Succinyl Co A is formed from propionyl CoA and α - ketoglutarate Propionyl CoA is formed from oxidation of odd chain FA,valine , isoleucine, methionine Utilization succinyl CoA is oxidized through TCA cycle Succinate is utilized for metabolism ketone bodies It is also used for synthesis of heme Role of succinyl CoA

14. Propionyl CoA is formed from oxidation of odd chain fatty acids, isoleucine, methionine & valine Utilization:- Propionyl CoA is converted to succinyl CoA Propionyl CoA

15. Acetyl CoA Ketone Bodies Pyruvate Fatty Acids Ketogenic amino acids CO 2 + H 2 O Ketone Bodies Fatty Acids Acetyl Choline Cholesterol

16. Rich soueces : Yeast, eggs, liver & meat Good sources:- vegetables & grains RDA: Adults - 10 mg/day Children - 7 mg/day Dietary sources

17. Deficiency of pantothenic acid (CoA) is rare in humans Experimental studies: By giving antagonist of B5 such as ω - methyl pantathenic acid Burning feet syndrome is observed It is characterized by numbness & tingling of toes, burning pain in the feet , sleep disturbances, dermatitis & depression Deficiency

18. 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