Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Concentrations of key metabolites were determined in carp white muscle before exercise and after maximal activity. It was found that the concentration of ATP decreases by about 65%, ADP decreases slightly, and AMP remains unchanged. Consequently, the level of the free adenylate pool decreases. Simultaneously there is an increase in the concentration of IMP and NH4+. The increase in IMP level and the decrease in adenylate pool are essentially in 1:1 stoichiometry, a result showing that the adenylate pool is decreased by the reaction catalyzed by 5'-AMP deaminase (EC 3.5.4.6.). During exercise there is an increase in levels of glucose-6-phosphate, fructose 6-phosphate, and fructose 1,6-diphosphate that, along with the decrease in ATP levels, can account for the increase in glycolytic flux by activation of phosphofructokinase and pyruvate kinase.
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PMID:Control of energy metabolism in fish white muscle. 13 93

Deamination of AMP in skeletal muscle sarcoplasmic reticulum followed by an increase in pH from 6,5 up to 8,0 leads in a liberation of part of Ca2+ from the SR vesicles. This effect is enhanced by K+, which activate the deamination, and is suppressed by Mg2+, which inhibit the reaction. The activating effect of AMP on Ca2+ efflux from the vesicles markedly decreases after AMP deaminase dissociation from the vesicles and is restored after reconstitution of their deaminase activity. Substitution of IMP for AMP causes a decrease of Ca2+ efflux from the vesicles. The data obtained are in good agreement with the assumption that the ammonium formation from AMP can favour the release of Ca2+ from some vesicles of SR.
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PMID:[Efflux of Ca2+ from fragmented sarcoplasmic reticulum during AMP deamination]. 50 58

Kinetic studies with adenylate deaminase have been performed by stopped flow methods at 20 degrees C in 0.01 M imidazole/HCl, pH 6.5. The data were analyzed using either the whole time course of the reaction or the initial portion of the full time course. At low KCl concentrations, activation by the product IMP complicates any interpretation. In the presence of 0.15 M KCl, the results are interpreted in terms of three types of purine nucleotide binding sites: an active site, an inhibitory site which appears to be relatively specific for nucleoside triphosphates, and an activating site which shows relatively little specificity for nucleoside phosphates. Nucleotide binding to the activating site weakens binding to the inhibitory site. Sigmoidal kinetic data observed as a function of AMP in the presence of the inhibitor GTP are interpreted in terms of AMP binding to the activating site and weakening GTP binding. A fragment of myosin, subfragement-2, which has previously been shown to form a tight complex with adenylate deaminase (Ashby, B., and Frieden, C. (1977) J. Biol. Chem. 252, 1869--1875) activates the deaminase reaction only slightly. Complex formation, however, makes the reaction less susceptible to inhibition by GTP, although high levels of this nucleotide will disrupt the complex. In the presence of GTP or GTP plus subfragment-2, hysteretic effects are observed.
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PMID:Adenylate deaminase. Kinetic and binding studies on the rabbit muscle enzyme. 72 7

Adenine and adenosine metabolism has been studied in intact human erythrocytes in vitro using high performance liquid chromatography, isotopic labeling and electrophoresis. Their metabolism to nucleotides was controlled by phosphoribose diphosphate synthesis which was phosphate dependent. Adenosine formed hypoxanthine or IMP depending upon Pi concentration, but adenosine kinase and deaminase activities were not affected by P levels. Free [14C]adenine and [14C]hypoxanthine were found in cellular extracts. Rapid interconversions occurred to give a distribution for ATP : ADP : AMP of 10 : 1 : 0.1. Marked decomposition of ATP to ADP and AMP occurred during incubations in plasma and Earle's media in air on nitrogen, but ATP levels remained stable in phosphate buffers and in the presence of oxygen. At physiological Pi (1 mM) adenosine kinase activity grossly exceeded adenine phosphoribosyltransferase activity. The latter was approximately 7 fold that of hypoxanthine phosphoribosyltransferase activity. These differences decreased with increasing Pi levels. No significant increase in corresponding nucleotides was obtained by incubation with high levels (0.5 mM) of adenine, guanine or guanosine at physiological Ii, ATP increased by 10% independently of the substrate employed and significant amounts of IMP and GTP were formed adenosine and guanosine, respectively. The existence of a bound intracellular pool of ATP is suggested.
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PMID:Studies on adenine and adenosine metabolism by intact human erythrocytes using high performance liquid chromatography. 94 98

Human B lymphoblast lines severely deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) were selected for resistance to 6-thioguanine from cloned normal and phosphoribosylpyrophosphate (PP-Rib-P) synthetase-superactive cell lines and were compared with their respective parental cell lines with regard to growth and PP-Rib-P and purine nucleotide metabolism. During blockade of purine synthesis de novo with 6-methylthioinosine or aminopterin, inhibition of growth of all HGPRT-deficient cell lines was refractory to addition of Ade at concentrations which restored substantial growth to parental cell lines. Ade-resistant inhibition of growth of parental lines by 6-methylthioinosine, however, occurred during Ado deaminase inhibition. Insufficient generation of IMP (and ultimately guanylates) to support growth of lymphoblasts lacking HGPRT activity and blocked in purine synthesis de novo best explained these findings, implying that a major route of interconversion of AMP to IMP involves the reaction sequence: AMP----Ado----Ino----Hyp----IMP. PP-Rib-P generation and purine nucleoside triphosphate pools were unchanged by introduction of HGPRT deficiency into normal lymphoblast lines, in agreement with the view that accelerated purine synthesis de novo in this deficiency results from increased availability of PP-Rib-P for the pathway. Cell lines with dual enzyme defects did not differ from PP-Rib-P synthetase-superactive parental lines in rates of PP-Rib-P and purine synthesis despite 5-6-fold increases in PP-Rib-P concentrations, excretion of nearly 50% of newly synthesized purines, and diminished GTP concentrations. Fixed rates of purine synthesis de novo in PP-Rib-P synthetase-superactive cells appeared to reflect saturation of the rate-limiting amidophosphoribosyltransferase reaction for PP-Rib-P. In combination with accelerated purine excretion, increased channeling of newly formed purines into adenylates, and impaired conversion of AMP to IMP, fixed rates of purine synthesis de novo may condition cell lines with defects in HGPRT and PP-Rib-P synthetase to depletion of GTP with consequent growth retardation.
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PMID:Regulation of purine nucleotide synthesis in human B lymphoblasts with both hypoxanthine-guanine phosphoribosyltransferase deficiency and phosphoribosylpyrophosphate synthetase superactivity. 131 6

The contribution of 5'-nucleotidase and AMP-deaminase to adenine nucleotide degradation in human cardiomyocytes isolated from diseased or normal heart was investigated. The preparation used contained 30 to 50% of viable cells and the nucleotide degradation was stimulated by addition of deoxyglucose and oligomycin. To distinguish pathways of nucleotide degradation, adenosine deaminase was inhibited by erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA). Under these conditions, ATP concentration was decreased by 60% after 45 min of incubation. Simultaneously, increases in intra- and extracellular catabolite concentrations have been observed. Adenosine was the predominant catabolite found in both the cells and in the extracellular medium accounting for more than 70% of all degradation products. Intracellular adenosine concentration rose to 300 times greater than that outside the cell. An increase in intra- and extracellular inosine was also seen. Only a small increase of IMP concentration was observed. No hypoxanthine accumulation was found. No significant change in initial adenine nucleotide concentrations were observed in isolated cells during aerobic incubation without deoxyglucose and oligomycin. In conclusion, a pathway involving adenosine production appears to be the principal route of nucleotide degradation in human cardiomyocytes.
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PMID:Adenine nucleotide catabolism and adenosine formation in isolated human cardiomyocytes. 156 34

A novel method for measuring AMP-deaminase activity in human erythrocytes is presented, based on the determination of the reaction product, IMP, using high performance liquid chromatography. IMP formation was found to be proportional both to the incubation time and the amount of haemolysate over a wide range. The minimal detectable AMP-deaminase activity was more than 1000 times lower than the mean activity found in healthy controls (1083 nmol/h/mg Hb). No marked difference of activity was found in the patients with the following inherited purine disorders: familial juvenile gouty nephropathy and deficiencies of adenosine deaminase, hypoxanthine-guanine phosphoribosyltransferase or adenine phosphoribosyltransferase. The activity in the erythrocytes of patients with chronic renal failure was also similar to controls. The existence of subjects with low erythrocyte AMP-deaminase activity in the population has been confirmed.
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PMID:A high performance liquid chromatographic assay for AMP-deaminase activity in the erythrocytes of healthy subjects and patients with inherited purine disorders. 191 25

Adenylic acid (AMP) deaminase is a "catabolic enzyme" involved in nucleotide degradation, transforming AMP into inosinic acid (IMP). We present a simple method for the determination of the enzyme activity, which combines high sensitivity with requirement of low quantities of lymphocytes. Human lymphocytes were isolated with a Lymphocyte Separation Medium from FLOW and sonicated. After centrifugation at 2,000 rpm x 10 min and treatment with Norit A, the cells were incubated at 37 degrees C with ATP 0.8 mM and 14C-AMP 0.1 mM (specific activity 12 microCi/mumole) in potassium phosphate 100 mM (pH 7.4). 14C-IMP and 14C-AMP were separated through HPLC by an isocratic elution, with 20 mM KH2PO4 (pH 5.5) at a 1.5 ml/min flow rate. Identification of the nucleotides was carried out through retention time, coelution with internal standards: their evaluation by determining the radioactivity of the collected peaks. The enzyme activity is decreased in patients affected by CLL: the decrease is evident only when data are referred to the single cells and not when they are referred to the protein.
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PMID:[Purine metabolism: determination of adenyl deaminase in human lymphocytes]. 239 Feb 25

The pathways of AMP degradation and the metabolic fate of adenosine were studied in cultured myotubes under physiological conditions and during artificially induced enhanced degradation of ATP. The metabolic pathways were gauged by tracing the flow of radioactivity from ATP, prelabelled by incubation of the cultures with [14C]adenine, into the various purine derivatives. The fractional flow from AMP to inosine through adenosine was estimated by the use of the adenosine deaminase (EC 3.5.4.4) inhibitors, coformycin and 2'-deoxycoformycin. The activities of the enzymes involved with AMP and adenosine metabolism were determined in cell extracts. The results demonstrate that under physiological conditions, there is a small but significant flow of label from ATP to diffusible bases and nucleosides, most of which are effluxed to the incubation medium. This catabolic flow is mediated almost exclusively by the activity of AMP deaminase (EC 3.5.4.6), rather than by AMP 5'-nucleotidase (EC 3.1.3.5), reflecting the markedly higher Vmax/Km ratio for the deaminase. Enhancement of ATP degradation by inhibition of glycolysis or by combined inhibition of glycolysis and of electron transport resulted in a markedly greater flux of label from adenine nucleotides to nucleosides and bases, but did not alter significantly the ratio between AMP deamination and AMP dephosphorylation, which remained around 19:1. Combined inhibition of glycolysis and of electron transport resulted, in addition, in accumulation of label in IMP, reaching about 20% of total AMP degraded. In the intact myotubes at low adenosine concentration, the anabolic activity of adenosine kinase was at least 4.9-fold the catabolic activity of adenosine deaminase, in accord with the markedly higher Vmax/Km ratio of the kinase for adenosine. The results indicate the operation in the myotube cultures, under various rates of ATP degradation, of the AMP to IMP limb of the purine nucleotide cycle. On the other hand, the formation of purine bases and nucleosides, representing the majority of degraded ATP, indicates inefficient activity of the IMP to AMP limb of the cycle, as well as inefficient salvage of hypoxanthine under these conditions.
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PMID:Pathways of adenine nucleotide catabolism in primary rat muscle cultures. 282

Uncertainties regarding the role of pyrimidine nucleotidase (PyrNase) in AMP catabolism were resolved by studies of erythrocytes from normal controls, controls with young mean cell ages, and patients with hereditary hemolytic anemia due to severe deficiency of PyrNase. Hemolysates from the latter exhibited undiminished capacity to dephosphorylate AMP over a broad range of pH, indicating that PyrNase was not directly involved. In each subject group, the rates of AMP dephosphorylation between pH 5.1 and 8.3 were indistinguishable from those of IMP, suggesting a potential role for AMP-deaminase, an erythrocyte enzyme that was stimulated by coformycin at pH 7.2. Quantitative analysis of catabolites in incubated hemolysates confirmed that AMP degradation preferentially occurred via deamination to IMP with subsequent dephosphorylation by another erythrocyte nucleotidase isozyme, deoxyribonucleotidase. Both AMP-deaminase and deoxyribonucleotidase have acidic pH optima with minimal activities at physiologic pH, suggesting that this pathway of AMP catabolism could accelerate depletion of the adenine nucleotide pool and thereby mediate the demise of senescent erythrocytes sequestered in the spleen.
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PMID:Mechanisms of adenosine 5'-monophosphate catabolism in human erythrocytes. 300 39


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