Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.5.4.4 (
adenosine deaminase
)
5,136
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The occurrence of a deficiency of
adenosine deaminase
(
ADA
) activity in some patients with severe combined immunodeficiency suggests a possible relationship between the activity of
ADA
and the aberration of the immune system. To help delineate the function of
ADA
in the immune response we have examined its role in monocyte maturation. When incubated in vitro, peripheral blood monocytes transformed, within 3 days, to macrophagea as assessed by phase-contrast microscopy and an increase in the specific activity of the lysosomal enzyme acid phosphatase. The specific activity of
ADA
increased as much as ninefold, reaching a peak after the 1st day in culture, while the activities of other enzymes involved in the purine salvage pathway were not altered.
Sucrose
density ultracentrifugation of extracts prepared immediately after the isolation of monocytes revealed the presence of two forms of
ADA
with molecular weights of approximately 30,000 and 110,000. The increase in
ADA
specific activity during monocyte cultivation correlated with an increase in the activity of the smaller molecular species. A specific inhibitor
ADA
, erythro-9-(2-hydroxy-3-nonyl) adenine, prevented the increase in acid phosphatase activity, as well as the morphological changes associated with the monocyte maturation. These data suggest a role for
ADA
in monocyte to macrophage maturation. In view of the central role of macrophages in immune function, this observation may relate to the association of combined immunodeficiency and a deficiency of this enzyme.
...
PMID:A role for adenosine deaminase in human monocyte maturation. 95 74
Near total inhibition of brain
adenosine deaminase
(
ADA
) activity in rats injected with the potent
ADA
inhibitor 2'-deoxycoformycin (DCF) was previously shown to reduce enzyme activity for up to 50 days during which time the enzyme exhibited reduced sensitivity to in vivo inhibition by DCF. Here, we investigated the biochemical properties of
ADA
and the basis for its reduced activity after DCF treatment. It was found that much higher doses of DCF were required to inhibit
ADA
in DCF-treated compared with drug-naive animals. Fourteen days after DCF administration, reduced
ADA
activity in brain homogenates was due to a decrease in Vmax, rather than to an altered Km of
ADA
for adenosine. DCF treatment had no effect on Ki values for erythro-9-(2-hydroxy-3-nonyl)adenine inhibition of
ADA
. The IC50 value for DCF inhibition of
ADA
in hypothalamus was unchanged. However, the Ki for DCF inhibition of
ADA
in whole brain increased by fivefold.
Sucrose
gradient analysis of brain
ADA
revealed only one corresponding peak of activity and [3H]DCF-labeled
ADA
in DCF-treated and control rats. A radioligand filtration assay with [3H]DCF was developed to assess the effects of DCF on
ADA
protein levels. Over a roughly 200-fold range of
ADA
activities the binding of [3H]DCF was highly correlated with deaminase activity (r = 0.99). In brain tissues taken 8 and 33 days after treatment of rats with DCF, [3H]DCF binding was reduced to 27% and 48% of control levels, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Rat brain adenosine deaminase after 2'-deoxycoformycin administration: biochemical properties and evidence for reduced enzyme levels detected by 2'-[3H]deoxycoformycin ligand binding. 172 90
