Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Inosine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1996

Effect of inosine supplementation on aerobic and anaerobic cycling performance.

Ten competitive male cyclists completed a Wingate Bike Test (WIN), a 30-min self-paced cycling performance bout (END), and a constant load, supramaximal cycling spring (SPN) to fatigue following 5 d of oral supplementation (5,000 mg.day-1) with inosine and placebo. Blood samples were obtained prior to and following both supplementation periods, and following each cycling test. Uric acid concentration was higher (P < 0.05) following supplementation with inosine versus placebo, but 2,3-DPG concentration was not changed. The data from WIN demonstrate that there were no significant differences in peak power (8.5 +/- 0.3 vs 8.4 +/- 0.3 W.kg body mass-1), end power (7.0 +/- 0.3 vs 6.9 +/- 0.2 W.kg body mass-1), fatigue index (18 +/- 2 vs 18 +/- 2%), total work completed (0.45 +/- 0.02 vs 0.45 +/- 0.02 kJ.kg body mass-1.30-s-1), and post-test lactate (12.2 +/- 0.5 vs 12.9 +/- 0.6 mmol.l-1) between the inosine and placebo trials, respectively. No difference was present in the total amount of work completed (6.1 +/- 0.3 vs 6.0 +/- 0.3 kJ.kg body mass-1) or post-test lactate (8.4 +/- 1.0 vs 9.9 +/- 1.3 mmol.l-1) during END between the inosine and placebo trials, respectively. Time to fatigue was longer (P < 0.05) during SPN for the placebo (109.7 +/- 5.6 s) versus the inosine (99.7 +/- 6.9 s) trial, but post-test lactate (14.8 +/- 0.7 vs 14.6 +/- 0.8 mmol.l-1) was not different between the treatments, respectively. These findings demonstrate that prolonged inosine supplementation does not appear to improve aerobic performance and short-term power production during cycling and may actually have an ergolytic effect under some test conditions.

2,3-Diphosphoglycerate↗
PubMed2002

Germination of Bacillus cereus spores in response to L-alanine and to inosine: the roles of gerL and gerQ operons.

Bacillus cereus 569 (ATCC 10876) endospores germinate in response to inosine or L-alanine, the most rapid germination response being elicited by a combination of these germinants. The gerI operon has already been characterized as a homologue of the gerA spore-germination receptor family of operons found in all Bacillus spp. examined; the primary defect in gerI mutant spores is in the inosine germination response, although spores were also slower to germinate in L-alanine. Additional transposon-insertion mutants, from similar Tn917-LTV1 mutagenesis and enrichment experiments, now define two more operons, also members of the family of gerA homologues, important in L-alanine and inosine germination. Transposon insertions were identified in an alanine-specific germination locus, named gerL, which represents an operon of three genes, termed gerLA, gerLB and gerLC. By examining the residual germination response to L-alanine in gerI and gerL mutants, it was deduced that the GerL proteins contribute most strongly to the L-alanine germination response, and that the GerI proteins, required primarily in inosine germination, mediate only much slower germination responses to alanine. The L-alanine germination responses mediated by GerL and GerI proteins differ in their germination rates, temperature optima and germinant concentration dependence. The gerQ locus, again identified by transposon insertion, is a second inosine-related germinant-receptor operon. GerQ and GerI proteins are both required for the germination response to inosine as sole germinant, but GerQ has no role in L-alanine germination. Although near-identical homologues of gerI and gerL operons are evident in the Bacillus anthracis genome sequence, there is no evidence of a close homologue of gerQ.

Alanine↗
PubMed1996

Role of inosine in prevention of methaemoglobinaemia in the pig: in vitro studies.

Methaemoglobin reductase activity was studied in pig, human and cattle erythrocytes incubated in a medium containing glucose or inosine as NADH generator. With glucose, methaemoglobin reduction was very fast in human, less so in cattle and slowest in pig erythrocytes. With inosine, pig red cells reduced methaemoglobin more rapidly than human red cells and in bovine erythrocytes the enzyme activity was undetectable. In intact red cells the ability to reduce methaemoglobin depends on the amount of NADH the cell can produce with glucose or inosine utilization. The results show that pig red blood cells utilize inosine as the NADH generator for enzymatic reduction of methaemoglobin. The greater efficiency of pig red cells could be due to several factors: better inosine transport, more active metabolic pathway for inosine utilization (so that more NADH is produced), or greater MR activity when NADH is in excess. In any case, the high rate of methaemoglobin reduction could explain the lower prevalence of methaemoglobinaemia in pigs than in cattle.

Animals↗
PubMed1989

Inosine causing insulin release and increased myocardial uptake of carbohydrates relative to free fatty acids in dogs.

The aim of the present study was to determine the effect of i.v. inosine on myocardial substrate uptake and function in the in situ dog heart. Inosine was infused i.v. at a rate of 5 mg kg min-1 in eight closed-chest pentobarbital anaesthetized dogs. Inosine caused a 46% decrease (P less than 0.01) in plasma free fatty acids (FFA), a 15% decrease (P less than 0.05) in plasma glycerol, an 18% decrease (P less than 0.05) in plasma glucose and a 46% increase (P less than 0.01) in blood lactate. This was associated with a 55% decrease (P less than 0.01) in myocardial FFA uptake and a 72% increase in lactate uptake, while glucose uptake remained unchanged. These metabolic changes were associated with a five-fold increase (P less than 0.05) in arterial insulin. Inosine caused an 18% increase (P less than 0.01) in myocardial blood flow without changing MVO2. There was a 33% increase (P less than 0.01) in LV dP/dtmax, a decrease in LVEDP from 4.9 +/- 0.9 (mean +/- SEM) to 0.9 +/- 0.3 mmHg (P less than 0.05) and a 24% decrease (P less than 0.01) in systemic vascular resistance. Inosine caused a transient 38% increase (P less than 0.05) in pulmonary vascular resistance. In conclusion, in addition to a positive inotropic effect and vascular effects inosine was found to cause release of insulin and to shift myocardial metabolism towards increased uptake of carbohydrates relative to FFA.

Animals↗
PubMed1981

The release of adenosine and inosine from canine subcutaneous adipose tissue by nerve stimulation and noradrenaline.

1. Plasma and adipose tissue purine nucleosides were assayed by reversed phase high-performance liquid chromatography after purification of the samples on phenylboronate affinity gel. 2. The adenosine content of unstimulated subcutaneous adipose tissue was close to 1 n-mole/g. The concentrations of adenosine and inosine in canine arterial plasma were 0.26 +/- 0.03 and 0.16 +/- 0.03 microM, respectively. In venous plasma from the canine subcutaneous adipose tissue the corresponding values were 0.32 +/- 0.04 and 0.28 +/- 0.06 microM under basal conditions. The arterio-venous concentration difference of adenosine was linearly dependent upon the arterial adenosine concentration. At arterial concentrations below 0.3 microM there was a net production of adenosine; above 0.3 microM there was a net extraction of approximately 77% of the adenosine. Adenosine was extensively eliminated in blood. The major part of this elimination could be accounted for by metabolism to inosine, hypoxanthine and uric acid. 3. Following sympathetic nerve stimulation (4 Hz for 20 min) the rate of adenosine outflow from adipose tissue increased from 0.33 +/- 0.22 to a peak value of 1.2 +/- 0.26 n-mole/min. This corresponds to a net release of 8.7 +/- 3.0 n-mole/100 g tissue. Inosine outflow rose from 0.64 +/- 0.37 to 5.3 +/- 1.4 n-mole/min, corresponding to a net release of 24.6 4/- 8.7 n-mole/100 g. Nerve stimulation also increased the release of [3H]purines from [3H]adenine pre-labelled adipose tissue. The fractional release increased 15-fold after stimulation. The radioactivity was mainly in the form of hypoxanthine, inosine and uric acid while adenosine was a minor component. When metabolism in blood was inhibited by dipyridamole and an adenosine deaminase inhibitor nerve-stimulation-induced release of [3H]purines was mainly in the form of adenosine. 4. Noradrenaline injection also induced a release of radioactive purines and of inosine. On the other hand, the outflow of endogenous adenosine was very small. 5. The present results demonstrate that under basal conditions adenosine is present in arterial and venous canine plasma. The free extracellular tissue level may be similar to the basal arterial adenosine concentration. Sympathetic nerve stimulation and noradrenaline induces a marked release of adenosine which is rapidly metabolized in the tissue and blood stream to inosine, hypoxanthine and uric acid. In adipose tissue the levels of adenosine reached after adrenergic stimulation appear high enough to be of physiological relevance.

Adenosine↗
PubMed2002

Inosine reduces inflammation and improves survival in a murine model of colitis.

Inosine, a naturally occurring purine formed from the breakdown of adenosine, has recently been shown to exert powerful anti-inflammatory effects both in vivo and in vitro. This study evaluated inosine as a potential therapy for colitis. Colitis was induced in mice by the administration of dextran sulfate sodium (DSS). Oral treatment with inosine was begun either before the onset of colitis or as a posttreatment once colitis was established. Evaluation of colon damage and inflammation was determined grossly (body wt, rectal bleeding), histologically, and biochemically (colon levels of MPO, MDA, and cytokines). DSS-induced colitis significantly increased inflammatory cell infiltration into the colon. DSS-induced colitis also increased colon levels of lipid peroxidation, cytokines, and chemokines. Inosine protected the colon from DSS-induced inflammatory cell infiltration and lipid peroxidation. Inosine also partially reduced these parameters in an experimental model of established colitis. Thus inosine treatment may be a potential therapy in colitis.

Animals↗
PubMed1982

Inosine: a protective agent in an organ culture model of myocardial ischemia.

Fetal mouse hearts in organ culture provide a model of ischemic-like injury in which the myocardial protective effect of pharmacological agents can be studied independent of blood flow. To investigate the potential protective effect of a diffusable purine under ischemic-like conditions, we used 4 mM inosine in fetal mouse heart organ cultures deprived of oxygen and oxidizable substrates for 1-10 hours. We studied hearts (n = 258) immediately after simulated ischemia (early) and after a 20-hour recovery period (late), by utilizing three indices of myocardial viability. Thallium-201 accumulation is an early marker of myocardial viability during injury, whereas the percentage of lactic dehydrogenase release from hearts to culture medium and the percentage of irreversibly injured myocytes assessed by planimetry of midventricular histological sections are late markers, used after recovery from injury. At 10 hours of injury, thallium-201 accumulation was 38% greater in inosine-supplied hearts, 3.50 +/- 0.16 vs. 2.54 +/- 0.08 (counts/min per mg wet weight)/(counts/min per microliter medium) (mean +/- SEM) (P less than 0.001). After recovery from 10 hours of injury, lactic dehydrogenase release was 29% less in inosine-supplied hearts, 35 +/- 3% vs. 49 +/- 3% (P less than 0.001). After recovery from 8 hours of injury, the percentage of histologically irreversibly injured tissue was 23% less in inosine-supplied hearts, 60 +/- 7% vs. 78 +/- 3% (P less than 0.05). These data indicate that inosine has a protective effect on fetal mouse myocardium during simulated ischemia and suggest that inosine deserves further evaluation.

Animals↗
PubMed1976

Latency of inosine-5'-diphosphatase in microsomes isolated from rat liver.

The latency of inosine-5'-diphosphatase has been studied in microsomes isolated from rat liver. The appearance of latent activity was the result of an increase in the Vmax of the enzyme. This was observed when assays were carried out in the presence of sodium deoxycholate, after microsomes were treated wtih phospholipase C, or at pH 10.3 and after microsomes were subjected to nitrogen cavitation. The apparent Km of inosine-5'-diphosphatase for IDP was unchanged when microsomes were treated with phospholipase C or at pH 10.3 after both these treatments approximately 85% of the enzyme remained bound to the membrane. In contrast, when microsomes were treated with phospholipase C or at pH 10.3 after both these treatments approximately 85% of the enzyme remained bound to the membrane. In contrast, when microsomes were treated with sodium deoxycholate or subjected to nitrogen cavitation, approximately 75% of the inosine-5'-diphosphatase activity was released from the membrane, and the apparent Km of the enzyme for IDP increased 4- and 2-fold, respectively. Microsomal cisternae were loaded with lead phosphate by incubation with glucose-6-P and Pb2+, and the release of this lead phosphate following the addition of EDTA to the medium was determined to estimate the permeability of the microsomal membrane. When microsomes were treated with sodium deoxycholate, phospholipase C, or at alkaline pH, the microsomal membrane became almost completely permeable to EDTA under conditions where there was little or no increase in the activity of inosine-5'-diphosphatase. Microsomes were treated at pH 10.3 and then adjusted slowly to pH 7.5. The activity of inosine-5'-diphosphatase decreased to the same activity observed in untreated preparations. The results seem of exclude the possibility that latent inosine-5'-diphosphatase activity is the result of an increased permeability of the membrane to IDP. They are, however, consistent with the presence of a noncompetitive inhibitor of the enzyme in the microsomal membrane.

Animals↗
PubMed1975

Incubation studies on human red cells utilizing glucose or inosine under various conditions.

Human red cells were incubated at pH 8.2 and 30 mM phosphate concentration with glucose, glucose plus methylene blue, or inosine. In 16 normal subjects, the lactate production rate (LPR) from glucose alone was 92.2 +/- 7.5 mumoles per minute per liter red blood cell. With methylene blue added, the mean LPR was 118.5 +/- 7.4 per cent of control glucose values. With inosine as substrate the mean LPR was 68.5 +/- 6.0 per cent of that from glucose. Lactate/glucose ratios averaged 1.36, presumably because of accumulation of intermediates under conditions of high pH and Pi. Patients with various kinds of anemias had LPR's from glucose that were usually markedly higher than normal, but the LPR's from inosine were generally about 2/3 of those from glucose. The LPR's of the anemic patients correlated with their degree of reticulocytosis and several patients with pyruvate kinase (PK) deficiency showed normal LPR if the red cell population age was ignored, byt marked depression when compared to expected LPR for degree of reticulocytosis. The LPR from glucose of red cells of G6PD-deficient subjects was decreased (not increased) by methylene blue. Methylene blue, while stimulating the pentose phosphate pathway, also mediated some oxidation of NADH, thus complicating the stoichiometry of the overall system. In addition, the results suggested that the dye may have attacked -SH groups on some enzymes. In normal red cells, the lower LPR from inosine than from glucose was explained as due to consumption of ATP for hexose utilization (thus generating more ADP for the triose reactions). In confirmation, when red cells were incubated without substrate to deplete their ATP-, and enhance their ADP-, levels, the LPR from inosine exceeded that from glucose. Fluoride and iodoacetate affected LPR from glucose more than from inosine, suggesting the necessity of adequate ATP levels in hexose utilization. Overall glycolysis in the red cell is seen as the resultant of a network of metabolic reactions in which ADP and ATP levels are important control parameters.

Adenosine Diphosphate↗
PubMed1978

[Indications for the use of inosine in myocardial infarct (a clinical and experimental study)].

The effect of the nucleoside Inosie-F (inosin) on the intracardiac hemodynamics and the contraction and relaxation of a diseased myocardium was studied in the clinic and in experiments. An examination was made of 102 patients with macrofocal myocardial infarction (22 received inosin by intravenous drip in a single dose of 200 mg in the acute stage of infarction; 60 patients were given inosin pills in a daily dose of 800 mg in the restoration period for one month, and 20 patients were given placebo). Comparative appraisal of treatment in the period of rehabilitation showed prevailing improvement in the condition of individuals treated with inosin, positive ECG dynamics, increase of cardiac output and decrease of peripheral resistance. In experiments on 28 dogs with a model of acute myocardial ischemia a noticeable improvement in myocardial contraction and relaxation in the absence of negative ECG dynamics was recorded after intravenous infusion of inosin. Inosin achieves maximum effect by 60-90 mins after the beginning of infusion.

Acute Disease↗
PubMed1988

Purification and properties of inosine-guanosine phosphorylase from Escherichia coli K-12.

A xanthosine-inducible enzyme, inosine-guanosine phosphorylase, has been partially purified from a strain of Escherichia coli K-12 lacking the deo-encoded purine nucleoside phosphorylase. Inosine-guanosine phosphorylase had a particle weight of 180 kilodaltons and was rapidly inactivated by p-chloromercuriphenylsulfonic acid (p-CMB). The enzyme was not protected from inactivation by inosine (Ino), 2'-deoxyinosine (dIno), hypoxanthine (Hyp), Pi, or alpha-D-ribose-1-phosphate (Rib-1-P). Incubating the inactive enzyme with dithiothreitol restored the catalytic activity. Reaction with p-CMB did not affect the particle weight. Inosine-guanosine phosphorylase was more sensitive to thermal inactivation than purine nucleoside phosphorylase. The half-life determined at 45 degrees C between pH 5 and 8 was 5 to 9 min. Phosphate (20 mM) stabilized the enzyme to thermal inactivation, while Ino (1 mM), dIno (1 mM), xanthosine (Xao) (1 mM), Rib-1-P (2 mM), or Hyp (0.05 mM) had no effect. However, Hyp at 1 mM did stabilize the enzyme. In addition, the combination of Pi (20 mM) and Hyp (0.05 mM) stabilized this enzyme to a greater extent than did Pi alone. Apparent activation energies of 11.5 kcal/mol and 7.9 kcal/mol were determined in the phosphorolytic and synthetic direction, respectively. The pH dependence of Ino cleavage or synthesis did not vary between 6 and 8. The substrate specificity, listed in decreasing order of efficiency (V/Km), was: 2'-deoxyguanosine, dIno, guanosine, Xao, Ino, 5'-dIno, and 2',3'-dideoxyinosine. Inosine-guanosine phosphorylase differed from the deo operon-encoded purine nucleoside phosphorylase in that neither adenosine, 2'-deoxyadenosine, nor hypoxanthine arabinoside were substrates or potent inhibitors. Moreover, the E. coli inosine-guanosine phosphorylase was antigenically distinct from the purine nucleoside phosphorylase since it did not react with any of 14 monoclonal antisera or a polyvalent antiserum raised against deo-encoded purine nucleoside phosphorylase.

Escherichia coli↗
PubMed1987

Study of the inhibition of histamine release by inosine pranobex.

The effects of Inosine pranobex and its parent compounds inosine and dimethylamino-2-propanol-p-acetamidobenzoic acid (DipPacBa) on the Concanavalin A (ConA)-induced histamine release from human adenoidal mast cells were investigated. Inosine pranobex inhibited the ConA-induced histamine release at concentrations greater than 10(-3) M. Inosine itself (10(-5)-10(-2) M) enhanced the ConA-induced histamine release whereas DipPacBa inhibited the release significantly at concentrations between 10(-6) and 10(-2) M. These results are consistent with the assumption that the effect of Inosine pranobex is due to the DipPacBa moiety.

Concanavalin A↗
PubMed2006

Development of inosine monophosphate and its degradation products during aging of pork of different qualities in relation to basic taste and retronasal flavor perception of the meat.

Inosine monophosphate (IMP) and its degradation products, ribose and hypoxanthine, are all considered to be important constituents in meat flavor formation and development. The present study explored the fate of IMP during the aging of two qualities of pork (pH >5.7 and 5.5 < pH < 5.6) and the potential relationship between IMP, hypoxanthine, and sensory attributes of pork registered both as retronasal and basic taste responses in whole meat, meat juice, and the remaining meat residue. During aging the concentration of IMP decreased with a simultaneous increase in the concentrations of inosine, hypoxanthine, and ribose. The rates at which IMP was degraded to inosine and inosine to hypoxanthine during aging were found to be in agreement with the known rate constants of the dephosphorylation of IMP and the hydrolysis of inosine, respectively. Moreover, high-pH pork resulted in a significantly higher concentration of hypoxanthine throughout storage compared with low-pH pork due to an initially higher concentration of IMP in high-pH meat. The sensory analysis showed increasing intensity in bitterness and saltiness of pork as a function of aging, with the intensity being most pronounced in the meat juice. The increasing bitterness of the pork as a function of aging coincided with the higher content of hypoxanthine in these samples, thereby suggesting that degradation of IMP to hypoxanthine might influence pork flavor. In contrast, IMP was associated with nonaged meat and the sensory attributes meaty and brothy.

Animals↗
PubMed1981

Activity of inosine triphosphate pyrophosphohydrolase in fresh and stored human erythrocytes.

The accumulation of inosine triphosphate (ITP) in human erythrocytes incubated with inosine depends on the activity of inosine triphosphate pyrophosphohydrolase (ITPH). High activity of this enzyme is accompanied by a low concentration of ITP and conversely. We showed that ITPH activity decreases with the prolongation of blood preservation time. As a consequence there is a lower accumulation of ITP in fresh erythrocytes incubated in a medium containing high concentrations of inosine, pyruvate and phosphate (IPP) than in red blood cells preserved at 4 degrees C. Synthesis of ITP in erythrocytes incubated in IPP medium being so intensive, it seems possible that during incubation an intermediate accumulates which decreases ITPH activity.

Blood Preservation↗
PubMed1995

Occurrence of inosine kinase as a distinct enzyme in Spirulina platensis.

Among a series of purine nucleosides, inosine was found to be phosphorylated at the highest rate by crude extracts of the cyanobacterium Spirulina platensis. The inosine phosphorylating activity could be separated from hypoxanthine-guanine phosphoribosyl transferase. This result shows that IMP formation may occur via the direct phosphorylation of inosine at its 5'-position, rather than via inosine phosphorolysis, followed by hypoxanthine phosphoribosylation, and provides unequivocal evidence for the occurrence of inosine kinase in nature.

Cyanobacteria↗
PubMed1996

Mechanism, specificity and general properties of the yeast enzyme catalysing the formation of inosine 34 in the anticodon of transfer RNA.

In yeast, inosine is found at the first position of the anticodon (position 34) of seven different isoacceptor tRNA species, while in Escherichia coli it is present only in tRNAArg. The corresponding tRNA genes all have adenosine at position 34. Using as substrates in vitro T7-runoff transcripts of 31 plasmids carrying each natural of synthetic tRNA gene harbouring an anticodon with adenosine 34, we have characterised a yeast enzyme that catalyses the conversion of adenosine 34 to inosine 34. The homologous E. coli enzyme modifies adenosine 34 only in tRNAs with an arginine anticodon ACG. The base conversion occurs by a hydrolytic deamination-type reaction. This was determined by reversed phase high-pressure liquid chromatography/electrospray mass spectrometry analysis of the reaction product after in vitro modification in [18O]water. This newly characterised tRNA:adenosine 34 deaminase was partially purified from yeast. It has a molecular mass of approximately 75 kDa, and it does not require any cofactor, except magnesium ions, to deaminate adenosine 34 efficiently in tRNA. The observed dependence of the enzymatic reaction on magnesium ions probably reflects the need for a correct tRNA architecture. Enzymatic recognition of tRNA does not depend on the presence of any "identify" nucleoside other than adenosine 34. Likewise, the presence of pseudouridine 32 or 1-methyl-guanosine 37 in the anticodon loop does not interfere with inosine 34 biosynthesis. However, the efficacy of adenosine 34 to inosine 34 conversion depends on the nucleotide sequence of the anticodon loop and its proximal stem, the best tRNA substrates being those with a purine at position 35. Mutations that affect the size of the anticodon loop or one of several three-dimensional base-pairs abolish the capacity of the tRNA to be substrate for the yeast tRNA:adenosine 34 deaminase. Evidently, the activity of yeast tRNA:adenosine 34 deaminase depends more on the global structural feature (conformational stability/flexibility) of the L-shaped tRNA substrates than on the identity of any particular nucleotide other than adenosine 34. An apparent K(m) of 2.3 nM for its natural substrate tRNASer (anticodon AGA) was measured. Altogether, these results suggest that a single enzyme can account for the presence of inosine 34 in all seven cytoplasmic A34-containing precursor tRNAs in yeast.

Adenosine↗
PubMed1989

Erythrocyte acid phosphatase (ACP1) activity. In vitro modulation by adenosine and inosine and effects of adenosine deaminase (ADA) polymorphism.

Erythrocyte acid phosphatase (ACP1) activity was determined in the absence of modulators and in the presence of either adenosine or inosine as modulators in 154 samples of red blood cells collected from adult donors. Adenosine and inosine showed modulating effects (activation), that were genotype dependent in the allele order pb less than pa less than pc; the activation by inosine was much higher than by adenosine. The modulating effect was dependent on adenosine deaminase (ADA) genotype: In carriers of ADA2 allele the activation with ACP1 phenotype A was lower and that with phenotypes CA and CB was higher than in ADA1/ADA1 subjects. In addition, the basic ACP1 activity (i.e., without modulators) also appeared to be dependent on ADA genotype: The lowest ACP1 activity was observed in A and BA subjects carrying the ADA2 allele. Since the deamination of adenosine to inosine associated with ADA2-1 phenotype is slower than that associated with ADA1, the interaction of ADA on ACP1 activity may in fact be explained by a lower intracellular concentration of inosine in ADA2 carriers and, therefore, by a lower modulating effect of this on acid phosphatase activity.

Acid Phosphatase↗
PubMed1981

Facilitated transport of inosine and uridine in cultured mammalian cells is independent of nucleoside phosphorylases.

The zero-trans uptake of uniformly and base-labeled inosine and uridine was measured a 25 degrees C in suspensions of Novikoff rat hepatoma cells, Chinese hamster ovary cells, mouse L cells, mouse S49 lymphoma cells and a purine-nucleoside phosphorylase-deficient subline thereof (NSU-1), and in monolayer culture of mouse 3T3 and L cells. The initial velocities of uptake of both nucleosides were about the same in all cell lines investigated, regardless of the position of the label or of the substrate concentration between 3 and 300 microM or whether or not the cells possessed uridine or purine-nucleoside phosphorylase activity. The kinetic parameters for the facilitated transport of uridine and inosine were also similar in phosphorylase positive and negative cell lines (K = 120--260 microM and V = 6--40 pmol/microliters cell water per s) and the transport activities of the cells exceeded their total phosphorylase activities by at least 10-fold for uridine and 1--2-fold for inosine. Chromatographic fractionation of the intracellular contents and of the culture fluid showed that the free nucleosides appeared intracellularly prior to and more rapidly than their phosphorolysis products. During the initial 20--60 s of uptake of U-14C-labeled nucleosides the rates of intracellular appearance of ribose-1-P and base were about the same. After several minutes of incubation, on the other hand, the main intracellular component was ribose-1-P whereas the base attained a low intracellular steady-state concentration and accumulated in the medium due to exit transport. Other nucleosides, dipyridamole and nitrobenzylthioinosine, specifically inhibited the transport of uridine and inosine, and depressed the intracellular accumulation of ribose-1-P and the formation of base commensurate with that inhibition. The data indicate that the metabolism of inosine and uridine by the various cell lines can be entirely accounted for by the facilitated transport of unmodified nucleoside into the cell followed by intracellular phosphorolysis.

Animals↗