ADENOSINE DEAMINASE

'''Adenosine deaminase''' (also known as 'ADA') is an enzyme ()involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues.

Contents

Reactions

Pathology

Isoforms

Clinical significance

See also

References

Reactions

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

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). ^[1]
Mutations causing it to be overexpressed are one cause of hemolytic anemia. ^[2]
There is some evidence that a different allelle (ADA2) may lead to autism.^[3]

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 dipeptidyl peptidase-4 (aka, CD26).

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

★ is an RNA-specific ADA.^[4]

★ ADAT (, , ) is a tRNA-specific ADA, changing the tRNA to allow for a wobble base pairing.

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 added prior to incubation so as to inhibit the enzymatic acivity of ADA1. It is the absence of ADA1 that causes SCID.

See also

★ Adenosine deaminase deficiency

References

1. Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry, Sanchez JJ, Monaghan G, Børsting C, Norbury G, Morling N, Gaspar HB, , , Ann. Hum. Genet., 2007
2. Elevated adenosine deaminase activity and hereditary hemolytic anemia. Evidence for abnormal translational control of protein synthesis, Chottiner EG, Cloft HJ, Tartaglia AP, Mitchell BS, , , J. Clin. Invest., 1987
3. Adenosine deaminase alleles and autistic disorder: case-control and family-based association studies, Persico AM, Militerni R, Bravaccio C, ''et al'', , , Am. J. Med. Genet., 2000
4. Genome Biology