PURINE & PYRIMIDINE PURINE & PYRIMIDINE METABOLISMMETABOLISM

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Nucleotide consists purine / pyrimidine Nucleotide consists purine / pyrimidine base, ribose/deoxyribose and phosphates.base, ribose/deoxyribose and phosphates.

Nucleoside consists purine/pyrimidine Nucleoside consists purine/pyrimidine base and ribose/deoxyribose.base and ribose/deoxyribose.

Purine base contains adenine, guanine Purine base contains adenine, guanine and hypoxanthine.and hypoxanthine.

Pyrimidine base contains cytosine, uracil Pyrimidine base contains cytosine, uracil and thymine.and thymine.

Biosynthesis of purine Biosynthesis of purine

It begins with PRPP(phosphoribosIt begins with PRPP(phosphoribosyyl phosphate) l phosphate) synthesis and PRPP synthase. Afterwards synthesis and PRPP synthase. Afterwards PRPP glutamyl amidotransferase . Those 2 PRPP glutamyl amidotransferase . Those 2 enzymes are the key regulatory enzymes for the enzymes are the key regulatory enzymes for the purine synthesis. IMP is synthesized and could purine synthesis. IMP is synthesized and could make AMP or GMP.make AMP or GMP.

It happens in almost most cells’ cytosol except It happens in almost most cells’ cytosol except human brain,polymorphonuclear leukocytes and human brain,polymorphonuclear leukocytes and erythrocytes.erythrocytes.

Purine salvage pathwayPurine salvage pathway

Liver is the major site of synthesis.Liver is the major site of synthesis. It contains phosphoribosylation by PRPP of free It contains phosphoribosylation by PRPP of free

purine to form purine mononucleotide such as purine to form purine mononucleotide such as adenine to AMP( with APRT) and hypoxanthine / adenine to AMP( with APRT) and hypoxanthine / guanine to IMP/ GMP( with HGPRT). guanine to IMP/ GMP( with HGPRT).

It contains too phosphoryl transfer from ATP to It contains too phosphoryl transfer from ATP to purine ribonucleoside such as adenosine kinase purine ribonucleoside such as adenosine kinase catalyzes adenosine to AMP.catalyzes adenosine to AMP.

Reduction of ribonucleoside Reduction of ribonucleoside diphosphate to diphosphate to

deoxyribonucleoside diphosphate.deoxyribonucleoside diphosphate.

The enzyme is ribonucleotide reductase The enzyme is ribonucleotide reductase complex and active only when cells are complex and active only when cells are activelyly synthesizing DNA. It requires activelyly synthesizing DNA. It requires thioredoxin, thioredoxin reductase and thioredoxin, thioredoxin reductase and NADPH.NADPH.

Pyrimidine synthesisPyrimidine synthesis

It starts with carbamoyl phosphate with It starts with carbamoyl phosphate with carbamoyl phosphate synthasecarbamoyl phosphate synthase IIII ( in ( in cytosol).cytosol).

PRPP will involve later in synthesis.PRPP will involve later in synthesis.Salvage pathway is not that important Salvage pathway is not that important

such as OPRT.such as OPRT.

Purine and pyrimidine biosynthesis are Purine and pyrimidine biosynthesis are coordinately regulated through PRPP.coordinately regulated through PRPP.

In purine synthesis is regulated through In purine synthesis is regulated through the first and second enzymes.the first and second enzymes.

In pyrimidine synthesis, carbamoyl In pyrimidine synthesis, carbamoyl phosphate synthase II is inhibited by UTP phosphate synthase II is inhibited by UTP and purine nucleotides, but activated by and purine nucleotides, but activated by PRPP. Aspartate transcarbamoylase PRPP. Aspartate transcarbamoylase inhibited by CTP but activated by ATP.inhibited by CTP but activated by ATP.

Purine CatabolismPurine Catabolism

Purines are catabolized to xanthine and Purines are catabolized to xanthine and uric acid in human.Uric acid then is uric acid in human.Uric acid then is secreted in urine.secreted in urine.

Gout is an arthritis that has hyperuricemia.Gout is an arthritis that has hyperuricemia.Lesch-Nyhan syndrome and Von Gierke Lesch-Nyhan syndrome and Von Gierke

disease are disorder of this purine disease are disorder of this purine catabolism.catabolism.

Pyrimidine catabolismPyrimidine catabolism

Pyrimidines are catabolized to Pyrimidines are catabolized to ββ-alanine -alanine and and ββ-aminoisobutyrate then secreted in -aminoisobutyrate then secreted in urine.urine.