Adenosine deaminase (ADA)
Adenosine deaminase is an enzyme that breaks down adenosine and deoxyadenosine; blocking it with pentostatin poisons lymphocytes, which is why the drug works in hairy cell leukaemia and some T-cell cancers.
Overview
Adenosine deaminase (ADA) converts adenosine to inosine and deoxyadenosine to deoxyinosine in the purine salvage pathway. Lymphocytes depend on it: children born without ADA have severe combined immunodeficiency because deoxyadenosine metabolites accumulate and kill developing lymphocytes. Pentostatin (deoxycoformycin) is a tight-binding ADA inhibitor that reproduces this toxicity on purpose in lymphoid cancers, producing durable remissions in hairy cell leukaemia; it is also used in T-cell leukaemias and lymphomas and in graft-versus-host disease.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · Adenosine deaminase is an enzyme that breaks down adenosine and deoxyadenosine; blocking it with pentostatin poisons lymphocytes, which is why the drug works in hairy cell leukaemia and some T-cell cancers.
- 1 · What it is
Adenosine deaminase is an enzyme that breaks down adenosine and deoxyadenosine; blocking it with pentostatin poisons lymphocytes, which is why the drug works in hairy cell leukaemia and some T-cell cancers.
- 2 · What goes wrong in cancer
ADA is a zinc-dependent hydrolase expressed in most tissues and at high levels in lymphoid cells.
- 3 · How drugs use it
1 product aims at Adenosine deaminase (ADA): small molecules. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
External identifiers
Biology
ADA is a zinc-dependent hydrolase expressed in most tissues and at high levels in lymphoid cells. Inhibiting it raises intracellular deoxyadenosine triphosphate, which blocks ribonucleotide reductase and DNA synthesis and triggers apoptosis, an effect most marked in lymphocytes with high deoxynucleoside kinase activity. Pentostatin binds the enzyme almost irreversibly; cladribine, the other purine analogue used in hairy cell leukaemia, is instead a substrate-resistant deoxyadenosine analogue.
- Lymphocytes and lymphoid tissue (high)
- Widely expressed in other tissues at lower levels
- Also present in plasma as extracellular ADA
Latest papers
topQuery for this target: (TITLE:"Adenosine deaminase" OR ABSTRACT:"Adenosine deaminase" OR TITLE:"ADA" OR ABSTRACT:"ADA") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Adenosine deaminase (ADA), not a curated reading list.
Similar pages
not linked directly; found by shared links- TreatmentCladribine
Shares Pentostatin, Hairy cell leukaemia.
- PersonSascha Dietrich
- TechnologyMultiparameter flow cytometry MRD
- PathwayIntrinsic apoptosis (BCL-2 family)
Shares Apoptosis, Chronic lymphocytic leukaemia.
- TreatmentIbrutinib
- TreatmentRituximab