Catabolism of purine and pyrimidine nucleotides and disorders associated with it.

 

Introduction:

• Both DNA and RNA are composed of various nucleotides. 

• Every nucleotide contains a base, sugar ribose/deoxyribose linked to phosphoric acid residues.

• Combination of base and sugar is called a nucleoside 

• A nucleoside linked to phosphoric acid is called a nudietide.

• Base + Sugar-------->Nucleoside 

• Base + Sugar + Phosphoric acid→ Nucleotide.

• 

Catabolism of purine and pyrimidine nucleotides:

• Degradation of purines and pyrimidines produces uric acid and urea,

• During purine nucleotide degradation, 5-nucleotidase removes the phosphate group from the nucleotide.  

• Adenosine is deaminated to inosine by adenosine deaminase, and inosine is hydrolyzed to hypoxanthine (its purine base) and D-ribose. 

• Hypoxanthine is successively oxidized to xanthine and then uric acid with the help of xanthine oxidase. Molecular oxygen is the electron acceptor in this complex reaction. 

• GMP catabolism also yields uric acid as an end product.  

• GMP is first hydrolyzed to guanosine, which is then cleaved to free guanine. 

• Guanine undergoes hydrolytic removal of its amino group to yield xanthine, which is converted to uric acid by xanthine oxidase. 

• Uric acid is the excreted end product of purine catabolism.

• The pathways for degradation of pyrimidines generally lead to ammonia production and thus to urea synthesis. 

Hyperuricemia and Gout:

• Higher levels of uric acid in the blood are termed hyperuricemia.

• The conditions are at their peak before and after the attack in Gout. 

• In gout, salts of uric acid cause typical chalky swellings called tophi. 

• The disorder is found mainly in males and is genetically determined. 

• Gout is controlled by Allopurinol, which inhibits the enzyme xanthine oxidase and prevents the formation of uric acid, few other drugs are also useful in the conditions

• Treatment of acute gout arthritis : 

• Drugs like NSAIDs, corticosteroids, adrenocorticotropic hormones, analgesics are used to treat acute attacks of gout.

• Prevention of acute attacks of gout : 

• Colchicine and NSAIDs are used to prevent gout attacks.

• Lowering serum urate concentration : 

• Drugs like Probenecid, Allopurinol are used to lower serum urate concentrations.

Commonly Asked Questions

1. Write a short note on hyperuricemia and gout.

2. Write a short note on the catabolism of purine and pyrimidine nucleotides and disorders associated with it.