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 [EC 3.5.4.17].[1] The class is (EC 3) for hydrolase. Hydrolases are enzymes that catalyze bond cleavage by reaction with water.[2] 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.[3][4]
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 Mn2+ (neutral or alkaline pH), F−, Fe3+, CN−, Co2+, Zn2+, and Hg2+.[1][5]
Species distribution
Adenosine-phosphate deaminase is found in most, if not all organisms in all tissues, however, muscle tissue is the richest source.[6] 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.[7] Specifically within marine mollusks, studies suggest that adenosine-phosphate deaminases are widely distributed across the phylum.[1] However, it was noticed that the pathways varied within each individual species, suggesting that different substrates are preferred within different species.[1] The source organisms for this enzyme are Porphyra crispata, Desulfovibrio desulfuricans, Aspergillus sp..[5]
Function
Within the cell, adenosine-phosphate deaminase is found within all tissues, but particularly higher in concentration within muscle tissue.[6] Kinetic properties of the enzyme vary widely based on the source and purification of the enzyme.[6] 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.[7] The initial step of AMP degradation is the conversion to xanthine into alternative routes, xanthosine or hypoxanthine.[8]
Crystal Structure
Molecular weight of adenosine-phosphate deaminase is 30000-60000 Da[5] or 15223 Da.[9] The number of amino acid sequences is 135. There are 0 transmembrane helices.[9]
Active Site
The turnover number for adenosine-phosphate deaminase is 690 ATP, 630 ADP, and 710 AMP. The km 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.[5] Natural substrates for this enzyme are 5'-AMP and H2O. The substrate spectrum is as follows:[5]
Nucleotides are organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver.
Inosinic acid or inosine monophosphate (IMP) is a nucleotide. Widely used as a flavor enhancer, it is typically obtained from chicken byproducts or other meat industry waste. Inosinic acid is important in metabolism. It is the ribonucleotide of hypoxanthine and the first nucleotide formed during the synthesis of purine nucleotides. It can also be formed by the deamination of adenosine monophosphate by AMP deaminase. It can be hydrolysed to inosine.
A nucleotidase is a hydrolytic enzyme that catalyzes the hydrolysis of a nucleotide into a nucleoside and a phosphate.
Nucleic acid metabolism is a collective term that refers to the variety of chemical reactions by which nucleic acids are either synthesized or degraded. Nucleic acids are polymers made up of a variety of monomers called nucleotides. Nucleotide synthesis is an anabolic mechanism generally involving the chemical reaction of phosphate, pentose sugar, and a nitrogenous base. Degradation of nucleic acids is a catabolic reaction and the resulting parts of the nucleotides or nucleobases can be salvaged to recreate new nucleotides. Both synthesis and degradation reactions require multiple enzymes to facilitate the event. Defects or deficiencies in these enzymes can lead to a variety of diseases.
Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.
Guanosine monophosphate synthetase, also known as GMPS is an enzyme that converts xanthosine monophosphate to guanosine monophosphate.
GMP reductase EC 1.7.1.7 is an enzyme that catalyzes the irreversible and NADPH-dependent reductive deamination of GMP into IMP.
In enzymology, an ADP deaminase (EC 3.5.4.7) is an enzyme that catalyzes the chemical reaction
In enzymology, an ATP deaminase (EC 3.5.4.18) is an enzyme that catalyzes the chemical reaction
In enzymology, a cytosine deaminase (EC 3.5.4.1) is an enzyme that catalyzes the chemical reaction
In enzymology, a dCTP deaminase (EC 3.5.4.13) is an enzyme that catalyzes the chemical reaction
In enzymology, a deoxycytidine deaminase (EC 3.5.4.5) is an enzyme that catalyzes the chemical reaction
In enzymology, a GTP cyclohydrolase IIa (EC 3.5.4.29) is an enzyme that catalyzes the chemical reaction
In enzymology, a guanosine deaminase (EC 3.5.4.15) is an enzyme that catalyzes the chemical reaction
In enzymology, a phosphoribosyl-AMP cyclohydrolase (EC 3.5.4.19) is an enzyme that catalyzes the chemical reaction
In enzymology, a pterin deaminase (EC 3.5.4.11) is an enzyme that catalyzes the chemical reaction
In enzymology, a S-adenosylhomocysteine deaminase (EC 3.5.4.28) is an enzyme that catalyzes the chemical reaction
In enzymology, a sepiapterin deaminase (EC 3.5.4.24) is an enzyme that catalyzes the chemical reaction
Inosine-5′-monophosphate dehydrogenase (IMPDH) is a purine biosynthetic enzyme that catalyzes the nicotinamide adenine dinucleotide (NAD+)-dependent oxidation of inosine monophosphate (IMP) to xanthosine monophosphate (XMP), the first committed and rate-limiting step towards the de novo biosynthesis of guanine nucleotides from IMP. IMPDH is a regulator of the intracellular guanine nucleotide pool, and is therefore important for DNA and RNA synthesis, signal transduction, energy transfer, glycoprotein synthesis, as well as other process that are involved in cellular proliferation.
The Purine Nucleotide Cycle is a metabolic pathway in protein metabolism requiring the amino acids aspartate and glutamate. The cycle is used to regulate the levels of adenine nucleotides, in which ammonia and fumarate are generated. AMP coverts into IMP and the byproduct ammonia. IMP converts to S-AMP (adenylosuccinate), which then coverts to AMP and the byproduct fumarate. The fumarate goes on to produce ATP (energy) via oxidative phosphorylation as it enters the Krebs cycle and then the electron transport chain. Lowenstein first described this pathway and outlined its importance in processes including amino acid catabolism and regulation of flux through glycolysis and the Krebs cycle.
1 2 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. PMID27334467.
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. PMID5940938.
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. PMID5773435.
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