Pyrimidines degradation

After removal of the phosphates by various phosphatases, the nucleosides are cleaved to the base by the same nucleoside phosphorylase that catalyzes the salvage reaction. The equilibrium constant for this reaction is near 1, so that it can go in either direction depending on the relative levels of the substrates and products. 

The nitrogen from the pyrimidine bases is removed by transamination and dumped onto glutamate. The carbon skeleton ends up as CO2. 

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Pyrimidine Synthesis Pyrimidine Salvage Pyrimidine Degradation... 

Kuhara T, Ohdoi C, Ohse M. Simple gas chromatographic-mass spectrometric procedure for diagnosing pyrimidine degradation defects for prevention of severe anticancer side effects. J Chromatogr B Biomed Sci Appl 2001 758 61-74. 

Aminoisobutyric acid Fasting, catabolism Pyrimidine degradation defects... 

Table 7.1.2 MS settings for pyrimidine degradation screening in the positive ESI mode ... 

Van Gennip AH, Abeling NGGM, Vreken P, van Kuilenburg ABP (1997) Inborn errors of pyrimidine degradation clinical, biochemical and molecular aspects. J. Inherit Metab Dis 20 202-213... 

Van Lenthe H, van Kuilenburg ABP, Ito T, Bootsma AH, van Cruchten AG, Wada Y, van Gennip AH (2000) Defects in pyrimidine degradation identified by HPLC-electrospray tandem mass spectrometry of urine specimens or urine-soaked filter paper strips. Clin Chem 46 1916-1922... 

The coexistence of different P2 receptors together with impure solutions caused by purine and pyrimidine degradation and interconversion as well as the lack of selective agonists and antagonists have led to some frustration in this field of research. 

Uric acid and urea are the end products of purine and pyrimidine degradation. 

Correct answer = E. The patient s pain is caused by gout, resulting from the crystallization of excess uric acid in his joints. The cell death caused by radiation therapy leads to the degradation of nucleic acids from those cells. The degradation of purines from these nucleic acids results in excess production of uric acid—a relatively insoluble compound that can cause kidney stones, as well as gout. The end products of pyrimidine degradation do not cause these problems, because they are all soluble compounds that can be more easily excreted in the urine. 

Since D-hydantoinase was identified as dihydropyrimidinase, it is proposed that D-amino acid production from DL-5-monosubstituted hydantoins involves the action of the series of enzymes involved in the pyrimidine degradation pathway. Based on this proposal, D-decarbamoylase was thought to be identical with P-ureidopropionase (EC 3.5.1.6) which functions in pyrimidine metabolism. 

Although both pyrimidines and purines are components in nucleic acids, they are made in different ways. Likewise, the products of pyrimidine degradation are more water-soluble than are the products of purine degradation. 

Know the purine and pyrimidine degradation pathways and the attendant pathologies. 

Rgure 7-22. Purine and pyrimidine degradation. Allopurinol (AP), which inhibits xanthine oxidase, is used to treat gout. 

Pyrimidine degradation produces no complex unique end products, but only common products. 

I.p-Alanine, 3-aminopropionic aid H2N-CH2-CH2-COOH, a nonproteogenic amino acid. It occurs in the free form, e. g. in human brain, and it is a component of the dipeptides, carnosine and anserine, and of coenzyme A. It is not usually formed by decarboxylation of L-aspartate, but rather in the course of reductive pyrimidine degradation. It can be further metabolized to acetate by deamination, decarboxylation and oxidation. 

Carbamoyl phosphate HjN-COO PO3H2, an energy-rich phosphoiylated carbamate and an important metabolic intermediate. Carbamic acid, NHjCOOH, is unstable in fi ee form. Carbamate removed hydrolytically fi om carbamyl compounds, e.g. ureidopropionic acid (see Pyrimidine degradation), decomposes immediately into COj and NHj. Cp. is a specific precursor of arginine and urea (see Urea cycle), and of pyrimidines via orotic acid (see Pyrimidine biosynthesis). 

Dihydrouracil an intermediate in Pyrimidine degradation (see). M, 114.10, m.p. 274°C. 5,6-Dihy-drouracil occurs as a rare base in some nueleie aeids. 

In addition to the relatively unspecific P, some P show a high specificity, e.g. 5 -nucleotidase from snake venom and 3 -nucleotidase from rye, which catalyse the hydrolysis of 5 -nucleotides or 3 -nucleotides to their respective nucleosides (see Purine degradation, Pyrimidine degradation). 

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