Adenosine deaminase
| Adenosine deaminase | ||
|---|---|---|
|
||
| Ribbon model of the ADA of domestic cattle ( Bos taurus ) with central zinc, according to PDB 1VFL | ||
| Properties of human protein | ||
| Mass / length primary structure | 362 amino acids | |
| Secondary to quaternary structure | Homodimer | |
| Cofactor | zinc | |
| Identifier | ||
| Gene name | ADA | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 3.5.4.4 , aminohydrolase | |
| Response type | hydrolysis | |
| Substrate | Adenosine + H 2 O | |
| Products | Inosine + NH 3 | |
| Occurrence | ||
| Parent taxon | Creature | |
| Exceptions | plants | |
| Orthologue | ||
| human | House mouse | |
| Entrez | 100 | 11486 |
| Ensemble | ENSG00000196839 | ENSMUSG00000017697 |
| UniProt | P00813 | P03958 |
| Refseq (mRNA) | NM_000022 | NM_001272052 |
| Refseq (protein) | NP_000013 | NP_001258981 |
| Gene locus | Chr 20: 44.62 - 44.65 Mb | Chr 2: 163.73 - 163.75 Mb |
| PubMed search | 100 |
11486
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The adenosine deaminase (ADA) is the enzyme that catalyzes the conversion of adenosine to inosine catalyzed . This reaction is part of the recycling of purine nucleotides in all living things except plants. In humans, ADA occurs in all tissues, but especially in T lymphocytes , where it is bound to DPP4 in the cell contacts between the lymphocyte and epithelium and therefore plays an important role in the immune response . Mutations in the ADA - gene can ADA deficiency and this to a congenital disorder of the immune system lead (SCID).
Elevated levels can be found in serous body fluids in infections with mycobacteria (e.g. in tuberculosis) as a highly sensitive detection method.
In addition to binding to DPP4, ADA stabilizes the A1 adenosine receptor in the plasma membrane. Inhibiting ADA in a colitis model resulted in a decrease in inflammation levels.
Clinical significance
The Hereditary adenosine deaminase deficiency is a very rare congenital metabolic disorder , in which the synthesis of dADP, DGDP, dUDP and dCDP is inhibited. The reason for this is an indirect inhibition of ribonucleotide reductase . Adenosine deaminase deaminates adenosine to inosine and deoxyadenosine to deoxyinosine. If there is an enzyme deficiency, it may a. to an accumulation of deoxyadenosine, which is increasingly phosphorylated to dATP . Increased concentrations of dATP inhibit ribonucleotide reductase, which inhibits the synthesis of the other deoxyribonucleotides . As a result, there is a disruption of DNA synthesis, which primarily hinders the proliferation of lymphocytes . Those affected develop u. a. a severe immunodeficiency ( Severe Combined Immunodeficiency , SCID).
Catalyzed reaction
+ H 2 O + NH 3 
The deamination of adenosine leads to the formation of inosine.
Individual evidence
- ↑ Search result UniProt EC 3.5.4.4
- ↑ UniProt P00813
- ^ Mathur PC, Tiwari KK, Trikha S and Tiwari D: Diagnostic Value of Adenosine Desaminase (ADA) Activity in Tubercular Serositis . In: Indian J Tuberc . 53, No. 1, 2006, pp. 92-95.
- Jump up ↑ Gracia E, Cortés A, Meana JJ, et al. : Human adenosine deaminase as an allosteric modulator of human A (1) adenosine receptor: abolishment of negative cooperativity for [H] (R) -pia binding to the caudate nucleus . In: J. Neurochem. . 107, No. 1, October 2008, pp. 161-170. doi : 10.1111 / j.1471-4159.2008.05602.x . PMID 18680557 .
- ↑ Antonioli L, Fornai M, Colucci R, et al. : Inhibition of adenosine deaminase attenuates inflammation in experimental colitis . In: J. Pharmacol. Exp. Ther. . 322, No. 2, August 2007, pp. 435-442. doi : 10.1124 / jpet.107.122762 . PMID 17488880 .
Web links
- D'Eustachio / reactome: (2'-deoxy) adenosine + H2O ⇒ (2'-deoxy) inosine + NH3