PYRIMIDINE DEGRADATION & DISORDERS

PYRIMIDINE DEGRADATION & DISORDERS

• 2.
   The pyrimidinenucleotides undergo similar reactions (dephosphorylation, deamination & cleavage of glycosidic bond) like that of purine nucleotides to liberate the nitrogenous bases cytosine, uracil & thymine.
• 3.
   The basesare then degraded to highly soluble products β-alanine & β- aminoisobutyrate.  These are the amino acids which undergo transamination & other reactions to finally produce acetyl CoA & succinyl CoA.
• 4.
   The pyrimidines(like purines) can also serve as precursors in the salvage pathway to be converted to the respective nucleotides.  This reaction is catalysed by pyrimidine phosphoribosyltransferase which utilizes PRPP as the source of ribose 5-phosphate.
• 5.
   Orotic aciduria: This is a rare metabolic disorder.  Characterized by the excretion of orotic acid in urine, severe anemia & retarded growth.  Enzyme deficiency: Orotate phosphoribosyl transferase & OMP decarhoxylase of pyrimidine synthesis
• 6.
   The conditioncan be treated by feeding cytidine or uridine.  They may be converted to UTP which can act as feedback inhibitor.  Orotic aciduria may also occur in ornithine transcarbamoylase deficiency (urea cycle enzyme) as carbamoyl phosphate accumulates due to defective conversion to citrulline.
• 7.
   This isconsidered as a secondary orotic aciduria.  Due to defect in ornithine transcarbamoylase (of urea cycle) causes the accumulation of carbamoyl phosphate.  This is then diverted for the increased synthesis & excretion of orotic acid.
• 8.
   Textbook ofBiochemistry-U Satyanarayana  Textbook of Biochemistry-DM Vasudevan