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In enzymology, an adenosine-phosphate deaminase (EC 3.5.4.17) is an enzyme that catalyzes the chemical reaction

5'-AMP + H₂O ${\displaystyle \rightleftharpoons }$ 5'-IMP + NH₃

Thus, the two substrates of this enzyme are 5'-AMP and H₂O, whereas its two products are 5'-IMP and NH₃.

Classification

This enzyme belongs to the family of hydrolases, those acting on carbon-nitrogen bonds other than peptide bonds, specifically in cyclic amidines. The systematic name of this enzyme class is adenosine-phosphate aminohydrolase. Other names in common use include adenylate deaminase, adenine nucleotide deaminase, and adenosine (phosphate) deaminase.

The EC number for adenosine-phosphate deaminase is . The class is (EC 3) for hydrolase. Hydrolases are enzymes that catalyze bond cleavage by reaction with water. The sub-class refers to adenosine-phosphate deaminase acting on carbon-nitrogen bonds, other than peptide bonds. The sub-sub-class refers to the type of substrate the enzyme is binding to, in this case, cyclic amidines. The final number (17) indicates that adenosine-phosphate deaminase binds to 5'-adenosine monophosphate.

Reaction mechanism

The pathway for adenosine-phosphate deaminase involves two substrates, 5'-adenosine monophosphate and water. This pathway is referred to as amidine hydrolysis. Adenosine-phosphate deaminase binds to 5'-AMP using water to break the C-N bond and replacing it with a carbonyl group. Ultimately, this produces 5'-IMP (Inosine monophosphate) and NH₃ (ammonia). Substrate specificities of this class depend on their origin, however, all of them deaminate adenosine, 2'-deoxyadenosine, 5'-AMP, and 3',5'-cyclic AMP. Inhibitors of adenosine-phosphate deaminase include Mn (neutral or alkaline pH), F, Fe, CN, Co, Zn, and Hg.

Species distribution

Adenosine-phosphate deaminase is found in most, if not all organisms in all tissues, however, muscle tissue is the richest source. The basic pathway of adenosine-phosphate deaminase is to replace a C-N bond of a 5'-AMP to replace the carboxyl group forming 5'-IMP. 5'-IMP is then catalyzed by Inosine-5'-monophosphate dehydrogenase (IMPDH) in guanine nucleotide biosynthesis. This is at the center of cell growth and proliferation. Specifically within marine mollusks, studies suggest that adenosine-phosphate deaminases are widely distributed across the phylum. However, it was noticed that the pathways varied within each individual species, suggesting that different substrates are preferred within different species. The source organisms for this enzyme are Porphyra crispata, Desulfovibrio desulfuricans, Aspergillus sp..

Function

Within the cell, adenosine-phosphate deaminase is found within all tissues, but particularly higher in concentration within muscle tissue. Kinetic properties of the enzyme vary widely based on the source and purification of the enzyme. Adenosine-phosphate deaminase binds to 5'-AMP performing hydrolysis, using water to break the C-N bond of the amino group attached to 5'-AMP. This results in binding 5'-IMP is then catalyzed by Inosine-5'-monophosphate dehydrogenase (IMPDH), facilitating guanine nucleotide biosynthesis. The initial step of AMP degradation is the conversion to xanthine into alternative routes, xanthosine or hypoxanthine.

Crystal Structure

Molecular weight of adenosine-phosphate deaminase is 30000-60000 Da or 15223 Da. The number of amino acid sequences is 135. There are 0 transmembrane helices.

Active Site

The turnover number for adenosine-phosphate deaminase is 690 ATP, 630 ADP, and 710 AMP. The k_m value is 0.047 for 5'-AMP. the pH optimum is 6.0-6.8 for 5'-AMP, however the pH range is 4-8 with a temperature optimum of 55 °C. Natural substrates for this enzyme are 5'-AMP and H₂O. The substrate spectrum is as follows:

Adenosine + H₂O

Adenosine phosphates + H₂O

NAD + H₂O

dATP + H₂O

dADP + H₂O

dAMP + H₂O

Deoxyadenosine + H₂O

The product spectrum is as follows:

Inosine + NH₃

Inosine phosphates + NH₃

Nicotinamide-hypoxanthine-dinucleotide + NH₃

dITP + NH₃

dIDP + NH₃

dIMP + NH₃

Deoxyinosine + NH₃

References

1. ^ Uchida H, Narita Y, Masuda A, Matsui Y, Chen YX, Takahashi I, Maeda S, Nomura A (January 1995). "Purification and Some Properties of Adenosine (Phosphate) Deaminase from the Liver of the Squid Todarodes pacificus". Bioscience, Biotechnology, and Biochemistry. 59 (7): 1276–1280. doi:10.1271/bbb.59.1276. ISSN 0916-8451.
2. Bornscheuer UT, Kazlauskas RJ (2006). Hydrolases in Organic Synthesis: Regio- and Stereoselective Biotransformatics (2nd ed.). Wiley-Blackwell. p. 1. ISBN 978-3-527-60712-9.
3. "EC 3.5.4". iubmb.qmul.ac.uk. Retrieved 2022-10-21.
4. "EC 3.5.4.17". iubmb.qmul.ac.uk. Retrieved 2022-10-21.
5. ^ Schomburg D, Salzmann M (1991). Enzyme Handbook 4. Springer. pp. 1059–1062. ISBN 978-3-642-84437-9.
6. ^ Smiley KL, Suelter CH (April 1967). "Univalent cations as allosteric activators of muscle adenosine 5'-phosphate deaminase". The Journal of Biological Chemistry. 242 (8): 1980–1981. doi:10.1016/S0021-9258(18)96097-7. PMID 6024785.
7. ^ Fotie J (2018-04-16). "Inosine 5'-Monophosphate Dehydrogenase (IMPDH) as a Potential Target for the Development of a New Generation of Antiprotozoan Agents". Mini Reviews in Medicinal Chemistry. 18 (8): 656–671. doi:10.2174/1389557516666160620065558. PMID 27334467.
8. "MetaCyc Reaction: 3.5.4.6/3.5.4.17". Biocyc.org. 1 March 2012.
9. ^ "Information on EC 3.5.4.17 - adenosine-phosphate deaminase - BRENDA Enzyme Database". www.brenda-enzymes.org. Retrieved 2022-10-21.

Further reading

• Su JC, Li CC, Ting CC (February 1966). "A new adenylate deaminase from red marine alga Porphyra crispata". Biochemistry. 5 (2): 536–543. doi:10.1021/bi00866a020. PMID 5940938.
• Yates MG (February 1969). "A non-specific adenine nucleotide deaminase from desulfovibrio desulfuricans". Biochimica et Biophysica Acta (BBA) - Enzymology. 171 (2): 299–310. doi:10.1016/0005-2744(69)90163-6. PMID 5773435.

• Biology

• EC 3.5.4
• Enzymes of unknown structure