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Literature summary for 6.3.2.6 extracted from

  • Goswami, M.T.; Chen, G.; Chakravarthi, B.V.; Pathi, S.S.; Anand, S.K.; Carskadon, S.L.; Giordano, T.J.; Chinnaiyan, A.M.; Thomas, D.G.; Palanisamy, N.; Beer, D.G.; Varambally, S.
    Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PPAT and PAICS in lung cancer (2015), Oncotarget, 6, 23445-23461 .
    View publication on PubMedView publication on EuropePMC
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Cloned(Commentary)

Cloned (Comment) Organism
gene PAICS, quantitative real-time RT-PCR enzyme expression analysis Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate Homo sapiens
-
 ADP + phosphate + (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
A-549 cell
-
 Homo sapiens
-
H-661 cell
-
 Homo sapiens
-
H-838 cell
-
 Homo sapiens
-
lung
-
 Homo sapiens
-
lung adenocarcinoma cell quantitative real-time RT-PCR measurement of purine biosynthesis metabolism enzymes PPAT, PAICS, PKM2 and PKM1 transcripts in lung adenocarcinomas, overview Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate
-
 Homo sapiens ADP + phosphate + (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
-
 ?

Synonyms

Synonyms Comment Organism
PAICS
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Homo sapiens

Expression

Organism Comment Expression
Homo sapiens regulation of both phosphoribosyl amidotransferase (PPAT) and phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), and of pyruvate kinase activity, by L-glutamine, a co-substrate for PPAT. A glutamine antagonist, 6-diazo-5-oxo-L-norleucine (DON) blocks glutamine mediated induction of PPAT and PAICS as well as reduced pyruvate kinase activity, which is completely reversible by addition of L-glutamate up

General Information

General Information Comment Organism
metabolism increased expression of the enzymes of de novo purine biosynthetic pathway in lung adenocarcinomas, phosphoribosyl amidotransferase (PPAT), phosphoribosylaminoimidazole carboxylase, and phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS). Modulation of PPAT and PAICS or glutamine treatment alters pyruvate kinase (PK) activity, overview Homo sapiens
physiological function enzyme phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) produces the intermediary metabolite N-succinyl-5-aminoimidazole-4-carboxamide-1-ribose-5'-phosphate (SAICAR), known to activate pyruvate kinase isoform PKM2 under glucose-depleted condi­tion. Increased expression of the enzymes of de novo purine biosynthetic pathway in lung adenocarcinomas, phosphoribosyl amidotransferase (PPAT), phosphoribosylaminoimidazole carboxylase, and PAICS. PAICS shows increased expression with disease progression and is significantly associated with poor prognosis. Altering PPAT and PAICS expression modulates pyruvate kinase activity, cell proliferation and invasion. Regulation of both PPAT and PAICS and pyruvate kinase activity by L-glutamine, a co-substrate for PPAT. PPAT and PAICS genes are necessary for lung tumorigenesis Homo sapiens