Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.1.1.205

Official Name

IMP dehydrogenase

Name from literature

Inosine monophosphate dehydrogenase

Pathway from literature

the de novo synthesis of guanine nucleotides from IMP

Pathway from KEGG

Nucleotide Metabolism; Purine metabolism; map00230

Xenobiotics Biodegradation and Metabolism; Drug metabolism - other enzymes; map00983

Organisms

Human (9606)

Genome localization

3p21.2[3615 ], 7q31.3-q32[3614 ],

Comments

The enzyme acts on the hydroxy group of the hydrated derivative of the substrate.

Rate-limiting Description

"Mycophenolic acid (MPA) is a highly selective, non-competitive and reversible inhibitor of the inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in the de novo biosynthesis of guanosine nucleotides." (17100698)

"Inosine-5'-monophosphate dehydrogenase (IMPDH) catalyzes the K+-dependent reaction IMP + NAD + H2O --> XMP + NADH + H+ which is the rate-limiting step in guanine nucleotide biosynthesis." (10194364)

"Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme required for the de novo synthesis of guanine nucleotides from IMP." (15940263)

"These properties reflect the fact that IMPDH is a rate-limiting enzyme in the new synthesis of the purine guanosine triphosphate (GTP), which modulates both exocytotic insulin secretion and DNA synthesis, as well as a number of other critical cellular functions within the beta-cell." (10417742)

"Inosine monophosphate dehydrogenase (IMPDH), a rate-limiting enzyme in the de novo synthesis of guanine nucleotides, is a major therapeutic target." (16243838)

"Studies have demonstrated that IMPDH is a rate-limiting step in the de novo synthesis of guanylates, including GTP and dGTP." (10390601)

"Recently, we demonstrated that downregulation of inosine-5'-monophosphate dehydrogenase (IMPD; IMP:NAD oxidoreductase, EC 1.2.1.14), the rate-limiting enzyme for guanine nucleotide biosynthesis, is required for p53-dependent growth suppression." (9766533)

"We evaluated a selection scheme based on the expression of a variant of inosine monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme in the de novo purine biosynthesis pathway." (16647299)

Regulatory Information

Upstream transcription factor

7157;7428

Regulatory type

Detail

transcriptional factor;p53 tumor suppressor(7157)

"IMPDH expression is downregulated by the p53 tumor suppressor gene." (10953293)

key enzyme;

"Inosine 5-monophosphate dehydrogenase II, a key enzyme in the de novo synthesis of purine nucleotides, is expressed in prostate tumors and prostate cancer cells." (18712736)

others;

"Mycophenolate mofetil up-regulates IMPDH-I and IMPDH-II mRNA in peripheral blood mononuclear cells. May predict acute rejection." (17713475)

others;

"C-terminal extension unique to the retinal isoforms blocks the nucleic acid binding site of IMPDH1, and thus uniquely regulates protein function within photoreceptors." (18295591)

phosphorylation;

P12268

phosphorylation;

P12268:from_uniprot:400_Phosphotyrosine

interact with TF;VHL(7428)

"Large-scale mapping of human protein-protein interactions by mass spectrometry." (17353931)

Gene ontology

Gene ontology

GO:0006177 (P) GMP biosynthetic process [P12268, P20839 ];
GO:0007601 (P) visual perception [P20839 ];
GO:0050896 (P) response to stimulus [P20839 ];
GO:0005829 (C) cytosol [P12268, P20839 ];
GO:0003938 (F) IMP dehydrogenase activity [P12268, P20839 ];
GO:0030955 (F) potassium ion binding [P12268, P20839 ];
GO:0005515 (F) protein binding [P12268 ];
GO:0055114 (P) oxidation reduction [P12268, P20839 ];

Tissue expression

Tissue From HPRD

Thymus [00895 ];
Colon [00895 ];
Fetus [00895 ];
Leukocyte [08853, 00895 ];
Testis [00895 ];
Skeletal muscle [00895 ];
Liver [00895 ];
Brain [08853, 00895 ];
Spleen [08853, 00895 ];
Prostate [00895 ];
Small intestine [00895 ];
Kidney [00895 ];
T Cell [00895 ];
Lung [00895 ];
Heart [00895 ];
Ovary [00895 ];
Pancreas [00895 ];
Placenta [00895 ];
Lymphocyte [08853 ];

Tissue specificity

IMP type I is the main species in normal leukocytes and type II predominates over type I in the tumor [P12268, P20839 ];

Disease relevance

Disease

Defects in IMPDH1 are the cause of retinitis pigmentosa type 10 (RP10) [MIM:180105]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP10 inheritance is autosomal dominant [P20839 ];

Links

SwissProt

P12268; P20839

Entrez Gene

3614; 3615

HPRD

08853; 00895



  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min