Enzyme adenosine deaminase

The molecule 7-aminopyrazolopyrimidine is related to the DNA base adenine. It is the base attached to ribose in formycin A, which is believed to have potential therapeutic value. It is also shown in Figure 5. There is a paradox in this system. This molecule is deactivated by the enzyme adenosine deaminase (ADA). In solution the N7H tautomer predominates. This structure however inhibits ADA, and this tautomer of formycin A would not be deactivated by the enzyme. 

A good example to illustrate these points is the antibiotic coformycin which inhibits the enzyme adenosine deaminase (Scheme 11.2) ... 

Severe combined immunodeficiency disease The enzyme adenosine deaminase degrades deoxyadenosine which is produced during DNA degradation (Chapter 10). Deficiency of the enzyme results in accumulation of deoxyadenosine which is a substrate for adenosine kinase and leads to production of deoxyadenosine and deoxyquanosine triphosphates, which reach high concentrations. This disturbs the balance of deoxy nucleotides which results in failure of DNA replication. This enzyme is normally present in lymphocytes so that a deficiency prevents proliferation of the lymphocytes, which is essential in combatting an infection. Consequently, patients are very susceptible to infections. This is one disease that is effectively treated by gene therapy. 

Pentostatin Nipent, deoxycoformycin) is a purine isolated from fermentation cultures of the microbe Streptomyces antibioticus. Its mechanism of action involves inhibition of the enzyme adenosine deaminase, which plays an important role in purine salvage pathways and DNA synthesis. The resulting accumulation of deoxyadenosine triphosphate (dATP) is highly toxic to lymphocytes. 

Enzymes Adenosine deaminase (ADA), PEG modified (bovine), [11-17 x PEG5000] Adagen 250IU/ml 1.5 ml vial, 15IU/kg weekly dose IM NA... 

Pteridine is changed by, the enzyme adenosine deaminase to the levorotatory form of the hydrate, 3,4-dihydro-4-hydroxypteridine. When this reaction was approached from the other direction, the same enzyme dehydrated this enantiomer most rapidly, leaving a net positive optical rotation at equilibrium.65 Specimens of the enzyme from both mammalian and fungal sources, although of very different molecular weight, were found to catalyze the stereospecific hydration of pteridine also pteridine inhibited the deamination of adenosine by both enzyme specimens. Assuming that the first step in the deamination of adenosine is the formation of a tetrahedral hydrated intermediate, it was argued that both the hydration of pteridine and the deamination of adenosine were parallel phenomena.65... 

Adenosine is degraded in a two-step reaction. First, the enzyme adenosine deaminase acts on AMP or adenosine nucleoside to yield IMP or inosine. 

A set of 4-amino-3-aryltriazoles, each one further substituted by a 5-amide, -ester, or -nitrile group, inhibited these enzymes adenosine deaminase, guanine deaminase, and xanthine oxidase. Structure-action relationships were discussed (79MI1 85FES73). 

An assay for adenosine involves the primary enzyme adenosine deaminase, and a chemical indicator reaction that consumes ammonia by reaction with the ninhy-drin reagent (Eq. 3.4) ... 

Gene therapy did receive a much-needed boost in 2002 when French scientists reported that they had apparently corrected severe combined immunodeficiency in a number of children using a retroviral-mediated protocol [35]. Severe combined immunodeficiency is a genetic condition caused by a deficiency of the enzyme adenosine deaminase, which triggers severe B and T lymphocyte dysfunction. However, celebrations were halted when a number of trial participants developed uncontrolled lymphoproliferation, a condition similar to leukemia. This halted - at least temporarily - several gene-therapy trials in various regions of the world [36]. 

The specificity of ethirimol towards mildews may be related to the presence in mildews of an unusual form of the enzyme adenosine deaminase, which is absent from other organisms. Differences in either the amount of this enzyme present or its sensitivity to ethirimol may explain why fungicide activity differs between mildew species (Hollomon, 1979b, Hollomon and Chamberlain, 1981). 

Pentostatin is a purine antimetabolite. It is a potent transition-state inhibitor of the enzyme adenosine deaminase (ADA) that leads to cytotoxicity because of elevated intracellular levels of dATP that can block DNA synthesis through inhibition of ribonucleotide reductase. Pentostatin can also inhibit RNA synthesis as well as cause increased DNA damage. It is indicated in the treatment for both untreated and alpha-interferon-refractory hairy-cell leukemia and as palliative therapy of chronic lymphocytic leukemia, prolympho-cytic leukemia and cutaneous T-cell lymphoma. 

Persons with severe combined immune deficiency (SCID) are totally unable to mount an immune response to antigens. Both the B and T lymphocytes are affected. The disease arises from an inherited lack of a degradative enzyme, adenosine deaminase (ADA). The reaction shown here illustrates the pathways affected. Lack of ADA allows deoxyadenosine triphophosphate (dATP) to accumulate from the degradation of DNA. High dATP levels inhibit production of the other dNTPs needed for DNA replication because of their allosteric effects on the enzyme ribonucleotide reductase. 

Recently, several but not all infants with the autosomal recessive form of the disease have been found to lack the enzyme adenosine deaminase (ADA) from their red cells and other tissues " ". Heterozygosity was detectable in their parents by their half normal levels of ADA . ... 

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