Download 6-Catabolism of Pyrimidine Nucleotides

CATABOLISM OF PYRIMIDINE
NUCLEOTIDES
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Dr. Shumaila Asim
Lecture # 6
PYRIMIDINE CATABOLISM

Pyrimidines are catabolized to β-alanine and βaminoisobutyrate then secreted in urine.
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Degradation of pyrimidine nucleotide
 The pyrimidine ring can be completely degraded in
humans.

The products include: NH3, CO2, b-alanine, and baminoisobutyrate.

Both b-alanine, and b-aminoisobutyrate can be further
converted into acetyl-CoA and succinyl-CoA,
respectively, or are excreted in the urine.
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Cytosine deaminase
Catabolism of
Pyrimidines
dihydrouracil dehydrogenase
dihydrouracil dehydrogenase
dihydropyrimidinase
dihydropyrimidinase
-ureidopropionase
-ureidopropionase
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PYRIMIDINE RELATED DISORDERS

Orotic acidurias

Deficiency of enzymes of urea cycle results in excretion of
pyrimidine precursors
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PYRIMIDINE RELATED DISORDERS
Orotic acidurias
Type – I
Deficiency of both orotate phospho-ribosyl transferase and
orotidylate decarboxylase
 Orotate & OMP cannot be converted to UMP ,CMP & TMP 
Orotate & OMP accumulate  inhibition of DNA & RNA synthesis

Type – II
Deficiency of only orotidylate decarboxylase
 OMP cannot be converted into UMP  inhibition of DNA / RNA
synthesis

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Pyrimidine Related Disorders
Deficiency of Urea Cycle enzymes
e.g. Deficiency of Ornithine trans-carbamoylase

Carbamoyl-phosphate cannot enter urea cycle

Exits into cytosol & stimulates pyrimidine synthesis

Leads to increased excretion of precursors of pyrimidines i.e. Orotic
acid, uracil and orotidine
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POINTS

Synthesis of Purine Nucleotides




De novo synthesis: Site, Characteristics, Element sources of purine bases
Salvage pathway: definition, significance, enzyme, Lesch-Nyhan
syndrome
Formation of deoxyribonucleotide: NDP level
Antimetabolites of purine nucleotides:


Degradation of Purine Nucleotides


Uric acid, gout
Synthesis of Pyrimidine Nucleotides

De novo synthesis: Characteristics, Element sources of pyrimidine bases
Salvage pathway
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Antimetabolites of pyrimidine nucleotides


Purine, Amino acid, and Folic acid analogs
Catabolism of Pyrimidine Nucleotides
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1.The key substance in the synthesis of purine, phosphoribosyl pyrophosphate
is formed by
(A) ribose 5-phosphate
(B) 5-phospho -ribosylamine
(C) D-ribose
(D) Deoxyribose
2. In purine biosynthesis ring closure in the molecule formyl glycinamide
ribosyl-5-phosphate requires the cofactors:
(A) ADP
(B) NAD
(C) FAD
(D) ATP and Mg++
3. Ring closure of formimidoimidazole carboxamide ribosyl-5-phosphate
yields the first purine nucleotide:
(A) AMP
(B) IMP
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(C) XMP
(D) GMP
4. The cofactors required for synthesis of adenylosuccinate are
(A)ATP, Mg++
(B) ADP
(C) GTP, Mg++
(D) GDP
5. Conversion of inosine monophosphate to xanthine monophosphate is
catalysed by
(A) IMP dehydrogenase
(B) Formyl transferase
(C) Xanthine-guanine phosphoribosyl transferase
(D) Adenine phosphoribosyl transferase
6. Phosphorylation of adenosine to AMP is catalysed by
(A) Adenosine kinase
(B) Deoxycytidine kinase
(C) Adenylosuccinase
(D) Adenylosuccinate synthetase
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7. Pyrimidine and purine nucleoside biosynthesis share a common
precursor:
(A) PRPP
(B) Glycine
(C) Fumarate
(D) Alanine
8.The first true pyrimidine ribonucleotide synthesized is
(A) UMP
(B) UDP
(C) TMP
(D) CTP
9. Methotrexate blocks the synthesis of thymidine monophosphate
by inhibiting the activity of the enzyme:
(A) Dihydrofolate reductase
(B) Orotate phosphoribosyl transferase
(C) Ribonucleotide reductase
(D) Dihydroorotase
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