Adenosine deaminase

adenosine deaminase
Ribbon diagram of bovine adenosine deaminase. Zinc ion visible at center. From PDB: 1VFL​
Identifiers
Symbol	ADA
NCBI gene	100
HGNC	186
OMIM	608958
RefSeq	NM_000022
UniProt	P00813
Other data
EC number	3.5.4.4
Locus	Chr. 20 q13.12
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Adenosine deaminase (also known as ADA) is an enzyme (EC 3.5.4.4)involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues.

Reactions

ADA irreversibly deaminates adenosine, converting it to the related nucleoside inosine by the removal of an amino group.

• Adenosine
  Adenosine
• 
  Inosine (observe missing nitrogen in upper left)

Inosine can then be deribosylated (removed from ribose) by another enzyme called purine nucleoside phosphorylase (PNP), converting it to hypoxanthine.

Pathology

Mutations in the gene for adenosine deaminase causing it to not be expressed are one cause of severe combined immunodeficiency (SCID).

Mutations causing it to be overexpressed are one cause of hemolytic anemia.

There is some evidence that a different allelle (ADA2) may lead to autism.

Isoforms

There are 2 isoforms of ADA: ADA1 and ADA2.

• ADA1 is found in most body cells, particularly lymphocytes and macrophages, where it is present not only in the cytosol and nucleus but also as the ecto- form on the cell membrane attached to a protein called CD26.

• ADA2 was first identifed in human thymus. It was subsequently found in other tissues including macrophage where it co-exists with ADA1 where the two isoforms regulate the ratio of adenosine to deoxyadenosine to potentiate the killing of parasites.

• An RNA-specific ADA also exists.

Clinical significance

ADA2 is the predominant form present in human blood plasma and is increased in many diseases, particularly those associated with the immune system: for example rheumatoid arthritis, psoriasis and sarcoidosis. The plasma AD2 isoform is also increased in most cancers.

Total plasma ADA can be measured using high performance liquid chromatography, enzymatic or colorimetric techniques. Perhaps the simplest system is the measurement of the ammonia released from adenosine when broken down to inosine. After incubation of plasma with a buffered solution of adenosine the ammonia is reacted with a Berthelot reagent to form a blue colour which is proportionate to the amount of enzyme activity. To measure ADA2, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) is then added to the reaction mixture so as to inhibit the ADA1. It is the absence of ADA1 that causes SCID.

See also

• Adenosine deaminase deficiency