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PubMed2005

Enterobacter meningitis: organism susceptibilities, antimicrobial therapy and related outcomes.

BACKGROUND: Meningitis due to Enterobacter species is an uncommon infection in adults; however, when present, treatment is frequently complicated by resistance of many Enterobacter isolates to third-generation cephalosporins and poor central nervous system penetration of other antibiotics. The aim of this study was to retrospectively review cases of meningitis caused by Enterobacter species at our institution, to better characterize patient factors, pathogen characteristics, and treatment options for this infection. METHODS: We reviewed all cases of Enterobacter meningitis in a 12-year period at a tertiary care center. Data collected included patient demographics, antibiotic sensitivities of Enterobacter isolates, antimicrobial therapy, and patient outcomes. RESULTS: Nineteen cases were identified, primarily in patients with neurotrauma and in neurosurgical patients. Enterobacter cloacae was the most frequent Enterobacter species isolated followed by Enterobacter aerogenes and Enterobacter agglomerans (50%, 34%, and 16% of cultures, respectively). Overall, clinical cure/improvement was achieved in 47% of patients, and the mortality rate was 21%. Antibiotic treatment varied substantially and included third-generation cephalosporins, intravenous and intrathecal aminoglycosides, trimethoprim-sulfamethoxazole (TMP-SMX), piperacillin, ciprofloxacin, and other miscellaneous antibiotics. Treatment with TMP-SMX was associated with a high rate of clinical cure/improvement, whereas third-generation cephalosporins were less efficacious. CONCLUSIONS: Enterobacter meningitis is an infrequent complication of neurological insult. Treatment is often complicated by resistance of Enterobacter species to third-generation cephalosporins. Our results indicate that while third-generation cephalosporins are not the most appropriate choice of agents to treat Enterobacter meningitis, TMP-SMX may yield satisfactory results.

Adult↗
PubMed2002

Urinary tract infection: traditional pharmacologic therapies.

Urinary tract infections (UTIs) are common bacterial infections, particularly in women. Antimicrobial therapy is seldom indicated for asymptomatic infection, but antimicrobial therapy is usually indicated for amelioration of symptoms. Management of acute uncomplicated UTI (cystitis) is generally straightforward, with a predictable distribution of uropathogens isolated. First-line treatment of acute uncomplicated UTI has traditionally involved a 3-day regimen of trimethoprim-sulfamethoxazole (TMP-SMX) or TMP alone for patients with sulfa allergies. Increasing resistance among community-acquired Escherichia coli to TMP-SMX worldwide has led to a reassessment of the most appropriate empiric therapy for these infections. Alternative first-line agents include the fluoroquinolones, nitrofurantoin, and fosfomycin. Factors to be considered in the selection of appropriate antimicrobial therapy include pharmacokinetics, spectrum of activity of the antimicrobial agent, resistance prevalence for the community, potential for adverse effects, and duration of therapy. Ideal antimicrobial agents for UTI management have primary excretion routes through the urinary tract to achieve high urinary drug levels. In addition, there are special considerations in the management of UTI among selected populations, including postmenopausal and pregnant women, and for women with frequent recurrent UTIs.

Adolescent↗
PubMed2002

The expanding role of fluoroquinolones.

There has been a growing rate of resistance among common urinary tract pathogens, such as Escherichia coli, to traditional antimicrobial therapies including the "gold standard" trimethoprim-sulfamethoxazole (TMP-SMX). Consequently, fluoroquinolone antimicrobial agents have taken on an expanding management role for UTIs. In fact, the recent Infectious Diseases Society of America clinical management guidelines for UTI recommend fluoroquinolones as first-line therapy for uncomplicated UTI in areas where resistance is likely to be of concern. Fluoroquinolones have demonstrated high bacteriologic and clinical cure rates, as well as low rates of resistance, among most common uropathogens. There are currently 7 fluoroquinolones with indications for UTI in the United States. However, only 3 are commonly used: levofloxacin, ciprofloxacin, and, to a lesser extent, gatifloxacin. Many of the fluoroquinolone agents have once-daily dosing regimens, enhancing patient adherence. In addition, levofloxacin and gatifloxacin have same-dose bioequivalency between their intravenous and oral formulations, allowing for "switch" or step-down therapy from parenteral to oral formulations of the same agent at the same dose. Fluoroquinolones are indicated for the management of acute uncomplicated UTIs, as well as complicated and severe UTI and pyelonephritis, in adults. They are the first-line treatment of acute uncomplicated cystitis in patients who cannot tolerate sulfonamides or TMP, who live in geographic areas with known resistance >10% to 20% to TMP-SMX, or who have risk factors for such resistance. Fluoroquinolone properties include a broad spectrum of coverage, low rates of resistance, and good safety profiles.

Anti-Infective Agents↗
PubMed2002

Urinary tract infection at the age extremes: pediatrics and geriatrics.

Urinary tract infections (UTIs) are common and generally benign conditions among healthy, sexually active young women without long-term medical sequelae. In contrast, UTIs are more complicated among those individuals at either end of the age spectrum: infants/young children and geriatrics. UTI in children younger than 2 years has been associated with significant morbidity and long-term medical consequences, necessitating an extensive and somewhat invasive imaging evaluation to identify possible underlying functional or anatomic abnormalities. Pediatric UTI should be considered complicated until proved otherwise, and treatment should reflect the severity of signs and symptoms. Management in the acutely ill child frequently involves parenteral broad-spectrum antimicrobial agents, and less ill children can be treated with trimethoprim- sulfamethoxazole (TMP-SMX), beta-lactams, and cephalosporins.UTI among older patients (>65 years) may be complicated by comorbidities, the baseline presence of asymptomatic bacteriuria, and benign urinary symptoms that can complicate diagnosis. The etiology of UTI encompasses a broader spectrum of infecting organisms than is seen among younger patients and includes more gram-positive organisms. Symptomatic UTI is generally more difficult to treat than among younger populations. Management should be conservative, of longer treatment durations, and cover a broad spectrum of possible uropathogens. Oral or parenteral treatment with a fluoroquinolone for 7 days is the preferred empiric approach. TMP-SMX can also be considered a first-line agent in women only, but only if the pathogen is known to be TMP-SMX sensitive.

Age Factors↗
PubMed2002

Cell-impermeant pyridinium derivatives of psoralens as inhibitors of keratinocyte growth.

Psoralens such as 8-methoxypsoralen and 4,5',8-trimethylpsoralen (TMP) are used in photochemotherapy for the treatment of a variety of epidermal proliferative diseases. Sequential treatments of the skin with psoralens plus ultraviolet light in the range of 320-400 nm (UVA light), referred to as PUVA therapy, results in the suppression of abnormal keratinocyte growth. With the recognition that the psoralens are phototoxic and carcinogenic, presumably due to their ability to intercalate into DNA and photo cross-link pyrimidine bases following UVA light activation, it is clear that the development of biologically active analogs lacking this activity would be of significant therapeutic benefit. Towards this goal we have characterized active 4'- and 5'-pyridinium derivatives of 4',5'-dihydro-TMP (H2TMP), a psoralen analog that does not form DNA cross-links. These analogs, which are charged at physiological pH and cannot penetrate cells, are unique in that they retain biological activity as inhibitors of keratinocyte cell growth when activated by UVA light. However, they do not appear to cross-link or damage DNA as determined by plasmid DNA unwinding and nicking experiments, in intact cells using fluorescent analysis of DNA unwinding assays, and by thymidine uptake studies. Reverse transcription-polymerase chain reaction and western blotting demonstrated that, unlike TMP and H2TMP, when activated by UVA light, the pyridinium derivatives were not inhibitors of transcription since interferon-gamma-inducible nitric oxide synthase mRNA and protein in the keratinocytes were unaffected. Taken together, our data suggest that uptake of the compounds by the cells and DNA cross-link formation are not required for growth inhibition. These findings further support the model that the cell membrane is an important target for the psoralens.

Animals↗
PubMed1998

Sensitivity to voltage-independent inhibition determined by pore-lining region of the acetylcholine receptor.

Some noncompetitive inhibitors (e.g., ganglionic blockers) exhibit selectivity for the inhibition of neuronal nicotinic acetylcholine receptors (nAChRs). This study characterizes the mechanism of selective long-term inhibition of neuronal and muscle-neuronal chimeric nAChRs by bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate (bis-TMP-10 or BTMPS), a bifunctional form of the potent ganglionic blocker tetramethylpiperidine. Long-term inhibition of neuronal nAChRs by bis-TMP-10 has been previously demonstrated to arise, at least in part, from the binding of the bis compound to neuronal beta-subunits. In this study, long-term inhibition is demonstrated to be dependent upon the presence of sequence element(s) within the pore-lining second transmembrane domain (tm2) of neuronal beta-subunits; however, the inhibitor binding site itself does not appear to be contained within the segment of the channel pore influenced by the membrane electric field. Specifically, our results imply that bis-TMP-10 interacts with an activation-sensitive element, the availability of which may be regulated by a sequence in the tm2 domain. Furthermore, we demonstrate a compound length requirement for long-term inhibition that would be consistent with binding to multiple sites located on the extracellular portion of the receptor.

Acetylcholine↗
PubMedDate not supplied

Antimicrobial susceptibility of Streptococcus suis isolates.

The antimicrobial activities of penicillin (PEN), ampicillin (AMP), cephalothin (CT), trimethoprim-sulphamethoxazole (TMP-SMX), streptomycin (STM), and gentamicin (GM) against 122 representative strains of Streptococcus suis, were compared by the agar dilution procedure. The current US National Committee for Clinical Laboratory Standards (NCCLS) breakpoints for non-enterococcal streptococci were used for PEN, AMP, CT, and TMP-SMX. Overall, 50% of strains were not fully susceptible to PEN, whereas these percentages for AMP and CT were 9% and 6% respectively. One strain was resistant to TMP-SMX. High-level GM resistance could not be detected, but more than 46% of strains were highly resistant to STM (MIC > 2000 mg l-1). This high percentage of resistance to STM precludes the use of this aminoglycoside-penicillin combination as empiric therapy in severe S. suis infections. These results should prompt microbiology laboratories to carry out antimicrobial susceptibility tests on a routine basis on S. suis isolates.

Animals↗
PubMed1985

Similar hematologic changes in children receiving trimethoprim-sulfamethoxazole or amoxicillin for otitis media.

We report the hematologic changes in 90 black children who were randomized to receive a 10-day course of either trimethoprim-sulfamethoxazole (TMP-SMZ) or amoxicillin as therapy for acute otitis media. Absolute neutrophil counts less than 1500/mm3 developed at least once during the 23-day evaluation in 28 (57%) of the 49 children given TMP-SMZ and in 22 (54%) of the 41 who received amoxicillin. Incidence of leukopenia, thrombocytopenia, and anemia was negligible in both groups. Pancytopenia did not occur in any child. Absolute neutrophil counts had increased to greater than 1500/mm3 by the end of the study period in all of the patients but six, whose recovery required an additional 1 to 63 days. Decreased neutrophil counts in antibiotic-treated subjects remained within the range of findings for healthy black children, suggesting that a count less than 1500/mm3 may be an inappropriate criterion for an adverse drug effect. Neither TMP-SMZ nor amoxicillin produced hematologic effects that would detract from their continued use in children with infections caused by antibiotic-susceptible organisms.

Amoxicillin↗
PubMed2001

Analysis of microfiltration performance with constant flux processing of secondary effluent.

This study involves the microfiltration (MF) of secondary effluent from a sequencing batch reactor processing industrial waste. The MF unit was a hollow fibre module with gas backwash capability, and operated with pumped permeate (controlled flux) and dead-end, crossflow or intermittent feed. The results showed that crossflow had no effect on flux and that intermittent dead-end filtration was less productive than non-intermittent operation. For dead-end filtration the cycle-time between gas backwashes depends very significantly on the imposed flux (varying from about 100 min at 30 L/m2 h to about 5 min at 90 L, m2 h) and the feed solids content. Optimal operation has to balance operating (energy for backwash) costs and the capital (membrane area) costs. Cost analysis based on capital and energy costs indicates that for lower energy cost the unit needs to be operated at lower imposed flux but to minimise total cost it is necessary to operate the unit above 60 L/m2 h imposed flux depending on the maximum transmembrane pressure (TMP) allowed before back washing. Further analysis of TMP profiles showed that membrane resistance increased over time towards a maximum, which tended to increase with imposed flux. This implies more frequent chemical cleaning for high flux operation. Specific cake resistances were deduced from the profiles and indicated cake compression at higher flux and larger maximum TMP. Results of long-term trials are also reported. Water quality analysis shows consistent quality of permeate

Equipment Design↗
PubMed1993

Hyperkalemia with high-dose trimethoprim-sulfamethoxazole therapy.

In a patient with the acquired immunodeficiency syndrome, a progressive increase in the serum potassium concentration occurred with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) therapy for Pneumocystis carinii pneumonia. In this patient, factors known to alter transcellular potassium shifts to induce hyperkalemia were not present. There was no evidence of glucocorticoid or mineralocorticoid insufficiency at the time of hyperkalemia, while the transtubular potassium gradient decreased. The hyperkalemia resolved spontaneously on discontinuation of TMP-SMX therapy, suggesting that this electrolyte abnormality is related to altered renal tubular secretion of potassium as a consequence of the high-dose TMP-SMX therapy.

AIDS-Related Opportunistic Infections↗
PubMed2003

A flow injection sensor for simultaneous determination of sulfamethoxazole and trimethoprim by using Sephadex SP C-25 for continuous on-line separation and solid phase UV transduction.

A flow-through sensor based on integration of spectrophotometric detection and the different kinetics of retention/elution of analytes on a solid support is proposed for the simultaneous determination of sulfamethoxazole (SMZ) and trimethoprim (TMP). The solid support (Sephadex SP C-25) fills both, a microcolumn placed on-line and the sensing microzone. The intrinsic absorbance of both compounds is monitored directly on the solid phase at 269 nm and so, no derivatization step is required. Using two alternate solutions, 10(-4) M hydrochloric acid and 0.20 M NaAc/HAc (pH 5.0) buffer, the sensor responds linearly in the measuring range of 50-250 and 10-70 microg ml(-1) with detection limits of 9.5 and 0.6 microg ml(-1) (500 microl of sample volume) for SMZ and TMP, respectively. The main advantages of the sensor are simplicity, rapidity and low reagents consumption. Its application to SMZ and TMP determination in synthetic samples and pharmaceutical preparations is demonstrated. The results obtained by the proposed method were compared with those obtained by a standard HPLC method.

Chromatography, High Pressure Liquid↗
PubMed2000

Molecular action of vitamin E in lipoprotein oxidation: implications for atherosclerosis.

The oxidation theory of atherosclerosis proposes that the oxidative modification of low-density lipoproteins (LDL) plays a central role in the disease. Although a direct causative role of LDL oxidation for atherogenesis has not been established, oxidized lipoproteins are detected in atherosclerotic lesions, and in vitro oxidized LDL exhibits putative pro-atherogenic activities. alpha-Tocopherol (alpha-TOH; vitamin E), the major lipid-soluble antioxidant present in lipoproteins, is thought to be antiatherogenic. However, results of vitamin E interventions on atherosclerosis in experimental animals and cardiovascular disease in humans have been inconclusive. Also, recent mechanistic studies demonstrate that the role of alpha-TOH during the early stages of lipoprotein lipid peroxidation is complex and that the vitamin does not act as a chain-breaking antioxidant. In the absence of co-antioxidants, compounds capable of reducing the alpha-TOH radical and exporting the radical from the lipoprotein particle, alpha-TOH exhibits anti- or pro-oxidant activity for lipoprotein lipids depending on the degree of radical flux and reactivity of the oxidant. The model of tocopherol-mediated peroxidation (TMP) explains the complex molecular action of alpha-TOH during lipoprotein lipid peroxidation and antioxidation. This article outlines the salient features of TMP, comments on whether TMP is relevant for in vivo lipoprotein lipid oxidation, and discusses how co-antioxidants may be required to attenuate lipoprotein lipid oxidation in vivo and perhaps atherosclerosis.

Animals↗
PubMed1999

Irradiation of titanium dioxide generates both singlet oxygen and superoxide anion.

Although photoexcited TiO2 has been known to initiate various chemical reactions, such as the generation of reactive oxygen species, precise mechanism and chemical nature of the generated species remain to be elucidated. The present work demonstrates the generation of singlet oxygen by irradiated TiO2 in ethanol as measured by ESR spectroscopy using 2,2,6,6-tetramethyl-4-piperidone (4-oxo-TMP) as a 1O2-sensitive trapping agent. Under identical conditions, the superoxide ion was also detected by spin trapping agent 5,5-dimethyl-pyrroline-N-oxide (DMPO). Kinetic analysis in the presence of both 4-oxo-TMP and DMPO revealed that singlet oxygen is produced directly at the irradiated TiO2 surface but not by a successive reaction involving superoxide anion. The basis for this view is the fact that DMPO added in the mixture increased the signals responsible for 4-oxo-2,2,6,6-tetramethyl-1-piperidinyloxy (4-oxo-TEMPO), a reaction product of 4-oxo-TMP and 1O2. The detailed mechanism for the generation of 1O2 and superoxide ion by irradiated TiO2 and reactions between these species and DMPO are discussed.

Electron Spin Resonance Spectroscopy↗
PubMed2003

Preparation of polyol esters based on vegetable and animal fats.

The possibility of using some natural fats: rapeseed oil, olive oil and lard, as starting material for the preparation of neopentyl glycol (NPG) and trimethylol propane (TMP) esters is reported. The syntheses of final products were performed by alcoholysis of fatty acid methyl esters, obtained from natural fats studied, with the appropriate polyhydric alcohol using calcium methoxide as a catalyst. The basic physicochemical properties of the NPG and TMP esters synthesized were the following: viscosity at 40 degrees C in the range of 13.5-37.6 cSt, pour point between -10.5 and -17.5 degrees C and very high viscosity indices, higher than 200. Generally, the esters of neopentyl alcohols were characterized by higher stability in thermo-oxidative conditions in comparison to native triglycerides. Due to the low content of polyunsaturated acids, the olive oil based esters showed the highest thermo-oxidative resistance. Also, methyl esters of fatty acids of lard would constitute a good raw material for the synthesis of lubricating oils, provided that their saturated acids content was lowered. This permits synthesis of NPG and TMP esters with a lower pour point (below -10 degrees C) than natural lard (+33 degrees C).

Conservation of Natural Resources↗
PubMed1997

Selective photoaffinity labelling of one mitochondrial protein in living cells of Saccharomyces cerevisiae with the fluorescent probe APMC. Identification of the target protein as subunit I of cytochrome c oxidase.

The lipophilic, cationic fluorochrome azopentylmethylindocarbocyanine (APMC) specifically stains the mitochondria in living yeast cells (Saccharomyces cerevisiae WT X 2180). It contains a photosensitive diazirine ring and is suitable for photoaffinity labelling. By combining photoaffinity labelling, micro-gel electrophoresis (SDS-PAGE), and detection of the APMC fluorescence with a microfluorimeter, we established a highly sensitive procedure for determining the apparent molecular weight of the APMC-labelled proteins in yeast cells. On vital staining at 0.1 microM APMC for 30 min, only one mitochondrial protein with an apparent molecular weight of 40 kDa is labelled with high intensity. At increased dye concentrations proteins of 47 and 49 kDa are labelled too, however not until all binding sites of the 40 kDa protein are occupied. Obviously, the APMC cations have a pronounced affinity for this protein. It was shown by fractional centrifugation that the labelled 40 kDa protein is a constituent of the inner mitochondrial membrane. One driving force for the accumulation of the APMC cations is the trans-membrane potential (TMP) across the inner mitochondrial membrane. Consequently, uncouplers like dinitrophenol (DNP) and carbonylcyanidechlorophenyl-hydrazone (CCCP), ionophores (valinomycin, gramicidin), and inhibitors of the respiratory chain (myxothiazol, KCN), which decrease the TMP, also diminish the APMC accumulation and labelling. And conversely, drugs, which hyperpolarize the inner membrane (nigericin, atractyloside), favour APMC labelling. Another driving force of APMC accumulation is the dye's lipophilicity, which facilitates dye accumulation by hydrophobic interaction with the very lipophilic proteins of the inner mitochondrial membranes. This was shown by competitive double staining experiments. Thiamine strongly inhibits APMC labelling. Obviously, the transport of the APMC cations is facilitated by the thiamine carrier, and thiamine competes for the same binding sites, which are occupied by the dye cations. Chloramphenicol is an inhibitor of the mitochondrial protein synthesis without affecting the TMP. On preincubation, chloramphenicol completely quenches the signal of the 40 kDa protein. Therefore, this protein must be encoded on the mtDNA. The only 40 kDa protein with adequate properties is the subunit I of cytochrome c oxidase. Obviously, it is the preferred target of the APMC cations on photoaffinity labelling. This assignment agrees with the strong hydrophobicity of the labelled 40 kDa protein, which was tested with various detergents. It also agrees with the solvatochromism of the protein-bound APMC label, and finally with the paralellism of the labelled protein with cytochrome c oxidase on fractional ammonium sulfate precipitation.

Carbocyanines↗
PubMed1999

Recurrent Pneumocystis carinii colonization in a heart-lung transplant recipient on long-term trimethoprim-sulfamethoxazole prophylaxis.

INTRODUCTION: In the setting of organ transplantation, prior to prophylaxis, Pneumocystis carinii pneumonia (PCP) had been a common clinical problem, particularly in heart-lung and lung recipients who receive long-term immunosuppressive therapy to prevent allograft rejection. Continuous oral trimethoprim-sulfamethoxazole (TMP-SMX) has been highly effective in preventing PCP in these patients. REPORT: In this paper we report a case of recurrent Pneumocystis carinii infection in a chronic (> 15 years) heart-lung allograft recipient on long-term TMP-SMX prophylaxis. Twice, in 1995 and again in 1998, Pneumocystis carinii infection was diagnosed by bronchoalveolar lavage (BAL), in the same patient, despite continued oral TMP-SMX (960 mg TMP/4800 mg SMX per week) prophylaxis. The subject was not lymphopenic (his CD4 count was 569/mm3) and there was no associated deterioration in pulmonary function, nor evidence of hypoxemia. CONCLUSION: This case demonstrates that asymptomatic Pneumocystis carinii lung infections may recur in chronic heart-lung transplant recipients who take standard oral PCP prophylaxis.

Administration, Oral↗
PubMed2006

The changing prevalence of drug-resistant Escherichia coli clonal groups in a community: evidence for community outbreaks of urinary tract infections.

A multidrug-resistant clonal group (CgA) of Escherichia coli was shown to cause half of all trimethoprim-sulphamethoxazole (TMP-SMZ)-resistant urinary tract infections (UTIs) in a college community between October 1999 and January 2000. This second study was conducted to determine the fate of CgA. Urine E. coli isolates from women with UTI, collected between October 2000 and January 2001, were tested for antibiotic susceptibility, O serogroup, ERIC2 PCR and DNA macrorestriction patterns using pulsed-field gel electrophoresis. The proportion of UTIs caused by CgA declined by 38% (P<0.001) but the prevalence of resistance to TMP-SMZ did not change. Six additional clonal groups were identified and these were responsible for 32% of TMP-SMZ-resistant UTIs. The temporal decline in the proportion of UTIs caused by CgA provides evidence that CgA caused a community outbreak of UTI. The fluctuation and occurrence of other E. coli clonal groups in this community suggest that a proportion of community-acquired UTIs may be caused by E. coli disseminated from one or more point sources.

Adolescent↗
PubMed1975

Hydrolysis of phosphonate esters catalyzed by 5'-nucleotide phosphodiesterase.

4-Nitrophenyl and 2-napthyl monoesters of phenylphosphonic acid have been synthesized, and an enzyme catalyzing their hydrolysis was resolved from alkaline phosphatase of a commerical calf intestinal alkaline phosphatase preparation by extensive ion-exchange chromatography, chromatography on L-phenylalanyl-Sepharose with a decreasing gradient of (NH4) 2SO4, and gel filtration. Detergent-solubilized enzyme from fresh bovine intestine was purified after (NH4)2SO4 fractionation by the same technique. The purified enzyme is homogeneous by polyacrylamide gel electrophoresis and sedimentation equilibrium centrifugation. It has a molecular weight of 108,000, contains approximately 21% carbohydrate, and has an amino acid composition considerably different from that reported from alkaline phosphatase from the same tissue. The homogeneous intestinal enzyme, an efficient catalyst of phosphonate ester hydoolysis but not of phosphate monoester hydrolysis, was identified as a 5'-nucleotide phosphodiesterase by its ability to hydrolyze 4-nitrophenyl esters of 5'-TMP but not of 3'-TMP. Also consistent with this identification was the ability of the enzyme to hydrolyze 5'-ATP to 5'-AMP and PPi, NAD+ to 5'-AMP and NMN, TpT to 5'-TMP and thymidine, pApApApA to 5'-AMP, and only the single-stranded portion of tRNA from the 3'-OH end. Snake venom 5'-nucleotide phosphodiesterase also hydrolyzes phosphonate esters, but 3'-nucleotide phosphodiesterase of spleen and cyclic 3',5'-AMP phosphodiesterase do not. Thus, types of phosphodiesterases can be conveniently distinguished by their ability to hydrolyze phosphonate esters. As substrates for 5'-nucleotide phosphodiesterases, phosphonate esters are preferable to the more conventional esters of nucleotides and bis(4-nitrophenyl) phosphate because of their superior stability and ease of synthesis. Furthermore, the rate of hydrolysis of phosphonate esters under saturating conditions is greater than that of the conventional substrates. At substrate concentrations of 1 mM the rates of hydrolysis of phosphonate esters and of nucleotide esters are comparable and both superior to that of bis(4-nitrophenyl) phosphate.

Amino Acids↗