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PubMed2002

SDT1/SSM1, a multicopy suppressor of S-II null mutant, encodes a novel pyrimidine 5'-nucleotidase.

SDT1 (suppressor of disruption of TFIIS 1, YGL224c, also known as SSM1, suppressor of S-II null mutant 1) is Saccharomyces cerevisiae gene identified as a multicopy suppressor of 6-azauracil sensitivity in a null mutant of the transcription elongation factor S-II. We found that overproduction of SDT1 caused hyposensitivity to not only 6-azauracil but also 5-fluorouracil and 5-fluorocytosine. This hyposensitivity was limited to pyrimidine derivatives, and no effect was observed for non-pyrimidine drugs including such clinically used anti-fungal drugs as amphotericin B and fluconazole. Purified recombinant SDT1 protein specifically dephosphorylated 5'-UMP and 5'-CMP. These results suggested that SDT1 conferred pyrimidine-specific hyposensitivity by dephosphorylating active metabolites of 6- or 5-modified pyrimidines, i.e. 6- or 5-modified UMP. This is the first description of a highly specific pyrimidine 5'-nucleotidase in S. cerevisiae.

5'-Nucleotidase↗

PubMed1995

5' UTR of hepatitis A virus RNA: mutations in the 5'-most pyrimidine-rich tract reduce its ability to direct internal initiation of translation.

The 5'-terminal untranslated region (5' UTR) of the uncapped hepatitis A virus (HAV) RNA contains two pyrimidine-rich sequences; one about 20 nucleotides (nt) in length in the vicinity of the AUG initiation codon (nt 706-726), and a longer one (about 40 nt) encompassing nt 100 to 140. The latter includes a 13 nt 'core' sequence (positions 126-138 in the HM175 strain) which is 80% identical to the pyrimidine-rich tract of poliovirus type 1 RNA (Mahoney strain). Representative cDNAs of the entire 5' UTR of HAV RNA were inserted in the intercistronic region of the bi-cistronic plasmid pSV-GH/CAT between the genes coding for the human growth hormone (GH) and bacterial chloramphenicol acetyltransferase (CAT). When COS-7 cells were transfected with these constructs they transiently expressed CAT indicating that the 5' UTR of HAV was efficiently directing internal initiation of translation of the reporter gene. Under similar conditions the 5' UTR of poliovirus type 2 (Lansing strain) was 30% more efficient in directing the expression of the CAT gene. Removal of the 'core' sequence from the 5'-distal pyrimidine-rich stretch extending between nt 117 and 131 in the HAV 5' UTR reduced the CAT activity in the lysates of transfected cells by 40%, whereas point mutations engineered in this segment strongly decreased (80% inhibition) the HAV-driven expression of the reporter gene. Limited mutations systematically introduced in the reiterated (U)UUUCCC motifs of the 5'-distal pyrimidine-rich tract identified two major functional domains extending between nt 100-106 and 113-119. Substitutions in these hexanucleotides abrogated internal initiation of translation, whereas similar changes in the neighbouring domains (nt 107-112 and 120-126) had no effect on the expression of the reporter gene, suggesting that the 5'-most pyrimidine-rich tract is indeed part of the structure(s) recognized by ribosomes and associated factors at initiation of translation and that the hexanucleotides 100-106 and 113-119 constitute an important part of it. Although HAV replicates better at 33 degrees C than at 37 degrees C, incubation of transfected cultures at 33 degrees C delayed the expression and slightly reduced the level of CAT activity in the cell lysates, but the overall effect of the mutations remained unchanged.

Animals↗

PubMed1982

Comparative Effects of Substituted Pyrimidines on Growth and Gibberellin Biosynthesis in Gibberella fujikuroi.

The fungicide alpha-(2,4-dichlorophenyl)-alpha-phenyl-5-pyrimidine methyl alcohol (triarimol) and four other structural analogs of this substance, in which one or more of the substituents were varied, were tested for their comparative effects on growth and gibberellin biosynthesis in the fungus Gibberella fujikuroi. Each of the five analogs tested was capable of inhibiting growth as measured by dry weight in 5-day-old cultures. Three of them [alpha-(2-chlorophenyl)-alpha-(4-chlorophenyl)-5-pyrimidine methyl alcohol, fenarimol; alpha-(2-chlorophenyl)-alpha-(4-fluorophenyl)-5-pyrimidine methyl alcohol, nuarimol; and triarimol] were effective at appreciably lower concentrations than the other two [alpha-(4-chlorophenyl)-alpha-(1-methylethyl)-5-pyrimidine methyl alcohol, experimental compound EL 509; and alpha-cyclopropyl-alpha-(4-methoxyphenyl)-5-pyrimidine methyl alcohol, ancymidol].All five substances also inhibited gibberellin production as measured by gibberellin content of fungus filtrates. The relative effectiveness of the compounds as inhibitors of growth and gibberellin production were similar. These analogs were also shown to inhibit ent-kaurene oxidation by microsomal preparations from fungal mycelia. Thus, the site of inhibition of gibberellin biosynthesis may be the same for the fungus as the one affected by this group of substances in higher plant tissues.The structure-activity relationships between the analogs are opposite to those observed in higher plant tissues. The fungicides fenarimol, nuarimol, and triarimol, which were most effective in inhibiting growth and gibberellin biosynthesis in the fungus, were much less effective than EL 509 and ancymidol in inhibiting growth and gibberellin biosynthesis in higher plants. These results indicate that the ent-kaurene oxidase systems from the two sources have somewhat different molecular characteristics, and thus, interact differently with this group of substances.

Journal Article↗

PubMed2000

Disappearance of intramolecular stacking due to one-atom movement or increment of a 'propylene linker' in pyrazolo[3,4-d]pyrimidine-based flexible models.

In the crystal structures of 4,6-dimethylthio-1-[3-(4, 6-dimethylthio-2H-pyrazolo[3, 4-d]pyrimidin-2-yl)propyl]-1H-pyrazolo[3,4-d]pyrimidine, C(17)H(20)N(8)S(4), and 1-[4-(4-methoxy-6-methylthio-1H-pyrazolo[3, 4-d]pyrimidin-1-yl)butyl]-5-methyl-6-methylthio-4, 5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one, C(18)H(22)N(8)O(2)S(2), only intermolecular stacking due to aromatic pi-pi interactions between pyrazolo[3,4-d]pyrimidinerings is present.

Journal Article↗

PubMed2002

Intermolecular stacking in pyrazolo[3,4-d]pyrimidine-based pentamethylene-linked flexible molecules.

The crystal structures of 1-[5-[4,6-bis(methylsulfanyl)-2H-pyrazolo[3,4-d]pyrimidin-2-yl]pentyl]-6-methylsulfanyl-4-(pyrrolidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine, C(22)H(29)N(9)S(3), and 6-methylsulfanyl-1-[5-[6-methylsulfanyl-4-(pyrrolidin-1-yl)-2H-pyrazolo[3,4-d]pyrimidin-2-yl]pentyl]-4-(pyrrolidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine, C(25)H(34)N(10)S(2), which differ in having either a pyrrolidine substituent or a methylsulfanyl group, show intermolecular stacking due to aromatic pi-pi interactions between the pyrazolo[3,4-d]pyrimidine rings.

Journal Article↗

PubMed1994

Evidence for a pyrimidine-nucleotide-specific initiation site (the i site) on Escherichia coli RNA polymerase. Proximity relationship with the inhibitor binding domain.

Escherichia coli RNA polymerase has two sites, the i and i + 1, for the binding of the first two substrates. The i site is template- and Mg(2+)-independent and purine-nucleotide-specific, whereas the i + 1 site is template- and Mg(2+)-dependent and shows no nucleotide preference. The specificity of the i site for purine nucleotides is well in accord with the fact that most promoters initiate with a purine nucleotide. But there are a few promoters that initiate with a pyrimidine nucleotide. Dinucleotide synthesis at these promoters is completely inhibited by rifampicin. Earlier studies have failed to identify an i site for pyrimidine nucleotides. In this paper, using a fluorescent analog of UTP, namely uridine 5'-[gamma-(5-sulfonic acid)naphthylamidate]-triphosphate, abbreviated as UTP[AmNS], we are able to show its binding to RNA polymerase, with a Kd of 0.8 microM, in the absence of Mg2+ and template. This suggests the presence of an i pyrimidine nucleotide site. The fact that UTP-[AmNS] is capable of initiating RNA synthesis from the i site is further evidenced by the abortive transcription analyses at the lac promoter. Fluorescence titration studies performed in the presence and absence of purine initiator molecules indicate that this site is different from the i purine site. Scatchard analysis of the above data indicates the presence of a single binding site for UTP[AmNS] in the absence of Mg2+. Moreover UTP[AmNS] binds to the core enzyme with a Kd of 3.0 microM implying that, unlike the i purine nucleotide site, the sigma protein confers a tighter binding of UTP-[AmNS] to the low-Kd site. Forster's energy transfer measurements using UTP[AmNS] as the donor and rifampicin as the acceptor have been used for estimation of the distance of the i pyrimidine nucleotide site from the rifampicin site. From these measurements, we infer that there is no direct interference of rifampicin with the first phosphodiester bond between two pyrimidine nucleotides.

Binding Sites↗

PubMed1992

[5-Fluoro (3H) pyrimidine-4-ones: synthesis, reactivity and pharmacological properties].

Fourteen fluoro pyrimidine-4-ones, four fluoro bispyrimidine-4-ones and two fluoro pyrimidine-4-ones with fused ring have been prepared. The reactivity of the carbonyl group of two pyrimidine-4-ones phosphorus oxychloride was studied. The 4-chloro pyrimidines reacted with ammonia or morpholine giving 4-substituted pyrimidines. Eight compounds are evaluated for their anti-inflammatory and anti-convulsivant properties: they were found to be weakly active against oedema and three of them protected rats form tonic convulsions.

Animals↗

PubMed1989

[Hemolytic anemia caused by pyrimidine 5'-nucleotidase (P5N) deficiency 15 years later. Apropos of 2 new cases of hereditary deficit and another one of lead poisoning].

Congenital pyrimidin 5'nucleotidase deficiency manifests as hemolytic anemia with basophilic stippling. In lead poisoning, anemia, basophilic stippling and inhibition of erythrocyte pyrimidin 5' deficiency are also observed. In the present work, we report two cases of hemolytic anemia secondary to congenital deficiency of pyrimidin 5' nucleotidase and another case secondary to lead poisoning. Since 1974, when pyrimidin 5' nucleotidase deficiency was isolated, is known that hemolysis is related to the accumulation of pyrimidin nucleotides within the erythrocytes that behave as metabolic inhibitors. However, the precise metabolic process whose inhibition leads to the shortening of erythrocytes half life has not been elucidated yet.

5'-Nucleotidase↗

PubMed1987

Potentiation of halogenated pyrimidine radiosensitizers in human carcinoma cells by beta-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran- 5,6-dione), a novel DNA repair inhibitor.

3,4-Dihydro-2,2-dimethyl-2H-naptho[1,2,-b]pyran-5,6-dione (beta-lapachone) is a novel DNA repair inhibitor. It was tested for synergistic X-ray-induced lethality in combination with several halogenated pyrimidine radiosensitizers. Logarithmic-phase growing human epidermoid laryngeal carcinoma (HEp-2) cells were allowed to incorporate pyrimidine analogues for 48 h (approximately two cell doublings) and then were X-irradiated and subjected to various posttreatments. beta-Lapachone synergistically increased the dose enhancement ratios (DERs) of all analogues screened, with the exception of the 2'-chloro derivative of 5-bromodeoxyuridine. For example, following 5-bromodeoxycytidine sensitization an X-ray DER value of 1.87 +/- 0.04 at 1% survival was increased to 3.51 +/- 0.42 due to a 4-h post-X-irradiation exposure to 4 microM beta-lapachone. Do and Dq values for halogenated pyrimidine-sensitized human epidermoid laryngeal carcinoma cells were decreased 1.4- to 5.4-fold and 1.4- to 4.0-fold, respectively. beta-Lapachone had little effect upon the cytotoxicities of unirradiated human epidermoid laryngeal carcinoma cells whether or not they were previously exposed to any of the halogenated pyrimidine radiosensitizers. beta-Lapachone treatment following X-irradiation of cells that had not incorporated a pyrimidine analogue exhibited DER values of 1.38 +/- 0.05 and 1.40 +/- 0.01 at 10 and 1% survival levels, respectively. beta-Lapachone enhanced the radiosensitization of deoxycytidine analogues to a greater extent than the structurally related deoxyuridine analogues. Greater DERs and lower Do and Dq values were found for deoxycytidine than for deoxyuridine analogue radiosensitizers following beta-lapachone treatment. This agent may improve presently used radiation therapies and enhance proposed strategies which utilize deoxycytidine analogue radiosensitization together with protection of normal tissues by tetrahydrouridine to achieve tumor-selective radiotherapy.

Bromodeoxycytidine↗

PubMed1996

Interaction of hemoglobin E and pyrimidine 5' nucleotidase deficiency.

A Bangladeshi family is described in which the genes for both hemoglobin E (Hb E) and pyrimidine 5' nucleotidase deficiency are segregating. An individual homozygous for both these conditions has a severe hemolytic anemia, whereas family members who are homozygous for Hb E are asymptomatic and those homozygous for pyrimidine 5' nucleotidase deficiency have the mild hemolytic anemia that is characteristic of this disorder. Globin-chain synthesis experiments have shown that the mechanism underlying the interaction between these two genotypes is a marked decrease in the stability of Hb E in pyrimidine 5' nucleotidase-deficient red blood cells (RBCs). It has also been found that in the enzyme-deficient RBCs in which Hb E is highly unstable, free alpha-chains, though not beta E-chains, acoumulate on the membrane. In view of the increasing evidence that the hemolysis associated with pyrimidine 5' nucleotidase deficiency results not only from an increase in the level of erythrocyte pyrimidines, but also from inhibition of the hexose monophosphate shunt activity in young erythrocytes, it is likely that the marked instability of Hb E in the enzyme-deficient cells results from oxidant damage acting on a mildly unstable Hb variant. These observations may have important implications for the better understanding of the pathophysiology of Hb E/beta-thalassemia, globally the commonest important form of thalassemia.

5'-Nucleotidase↗

PubMed2000

Active-site determination of a pyrimidine dimer glycosylase.

One mechanism for the repair of UV-induced DNA damage is the base excision repair pathway. The initial step in this pathway and the specificity for the type of damage that is to be repaired reside in DNA glycosylase/abasic (AP) lyases. Cleavage of the glycosyl bond of the 5' pyrimidine of a cyclobutane pyrimidine dimer is hypothesized to occur through the destabilization of the glycosyl bond by protonation of the base or sugar with a concomitant nucleophilic attack on C1' of the deoxyribose moiety. Based on mechanistic biochemical information from several glycosylase/AP lyases and the structural information on the bacteriophage T4 pyrimidine dimer glycosylase (T4-pdg), the catalytic mechanism has been investigated for the Chlorella virus pyrimidine dimer glycosylase (cv-pdg). As predicted from modeling studies and reaction mechanisms, the primary amine that initiates the nucleophilic displacement reaction could be trapped as a covalent imine intermediate and its identity determined by sequential Edman degradation. The primary amine was identified as the alpha-amino group on the N-terminal Thr2. Site-directed mutagenesis was subsequently used to confirm the conclusions that the alpha-amino group of cv-pdg is the active-site nucleophile.

Amino Acid Sequence↗

PubMed1993

Cerebrospinal fluid amino acids, purines and pyrimidines as a tool in the study of metabolic brain diseases.

After establishing more extended reference values for amino acids, purines and pyrimidines in cerebrospinal fluid (CSF) in infancy and childhood, we studied 1250 CSF-aliquots from patients who were undergoing a diagnostic lumbar puncture for diverse clinical indications. Our primary aim was to answer the question whether determination of the concentration of amino acids, purines and pyrimidines in CSF is a useful tool in screening for metabolic disorders in children with unexplained mental retardation. In unexplained mental retardation (95 patients) we observed varying abnormalities of CSF. These were reproducible in only 2 patients (a decrease of homocarnosine in combination with two unidentified compounds). Striking abnormalities in pyrimidine content which are limited to CSF are found in argininosuccinic aciduria and uraemia. In uraemia a general decrease in amino acids in CSF and increase of gamma-aminobutyric acid (GABA) was observed. The results obtained indicate that determination of amino acids, purines and pyrimidines in CSF is only of limited value in the diagnosis of unexplained mental retardation.

Adolescent↗

PubMed1995

Sensitive nonradioactive detection of UV-induced cyclobutane pyrimidine dimers in intact mammalian cells.

In this paper we present a sensitive procedure to determine specifically the induction as well as the removal of cyclobutane pyrimidine dimers in intact mammalian cells without radioactive labeling of the DNA. This technique allows the detection of DNA damage by UV doses as low as 0.1 J/m2. The method consists of gentle lysis of cell monolayers, high-salt treatment and incubation with the cyclobutane pyrimidine dimer-specific repair enzyme T4 endonuclease V, followed by alkaline unwinding, hydroxyapatite chromatography and fluorimetric DNA analysis. The number of T4 endonuclease V-sensitive sites correlates well with the amount of UV-induced cyclobutane pyrimidine dimers reported in the literature, indicating that these cyclobutane pyrimidine dimers are recognized quantitatively by the system. The assay is easily transferable to the detection of other types of DNA adducts by applying different damage-specific repair enzymes, providing a sensitive method to investigate the induction and the repair of DNA lesions without the use of radioactive labeling.

Alkalies↗

PubMed2006

Structure of T4 pyrimidine dimer glycosylase in a reduced imine covalent complex with abasic site-containing DNA.

The base excision repair (BER) pathway for ultraviolet light (UV)-induced cyclobutane pyrimidine dimers is initiated by DNA glycosylases that also possess abasic (AP) site lyase activity. The prototypical enzyme known to catalyze these reactions is the T4 pyrimidine dimer glycosylase (T4-Pdg). The fundamental chemical reactions and the critical amino acids that lead to both glycosyl and phosphodiester bond scission are known. Catalysis proceeds via a protonated imine covalent intermediate between the alpha-amino group of the N-terminal threonine residue and the C1' of the deoxyribose sugar of the 5' pyrimidine at the dimer site. This covalent complex can be trapped as an irreversible, reduced cross-linked DNA-protein complex by incubation with a strong reducing agent. This active site trapping reaction is equally efficient on DNA substrates containing pyrimidine dimers or AP sites. Herein, we report the co-crystal structure of T4-Pdg as a reduced covalent complex with an AP site-containing duplex oligodeoxynucleotide. This high-resolution structure reveals essential precatalytic and catalytic features, including flipping of the nucleotide opposite the AP site, a sharp kink (approximately 66 degrees ) in the DNA at the dimer site and the covalent bond linking the enzyme to the DNA. Superposition of this structure with a previously published co-crystal structure of a catalytically incompetent mutant of T4-Pdg with cyclobutane dimer-containing DNA reveals new insights into the structural requirements and the mechanisms involved in DNA bending, nucleotide flipping and catalytic reaction.

Base Sequence↗

PubMed2006

Comparative studies on pyrimidine metabolism in excised cotyledons of Pinus radiata during shoot formation in vitro.

Changes in the pattern of pyrimidine nucleotide metabolism were investigated in Pinus radiata cotyledons cultured under shoot-forming (SF; +N(6)-benzyladenine) and non-shoot-forming (NSF, -N(6)-benzyladenine) conditions, as well as in cotyledons unresponsive (OLD) to N(6)-benzyladenine. This was carried out by following the metabolic fate of externally supplied (14)C-labeled orotic acid, intermediate of the de novo pathway, and (14)C-labeled uridine and uracil, substrates of the salvage pathway. Nucleic acid synthesis was also investigated by following the metabolic fate of (14)C-labeled thymidine during shoot bud formation and development. The de novo synthesis of pyrimidine nucleotides was operative under both SF and NSF conditions, and the activity of orotate phosphoribosyltransferase (OPRT), a key enzyme of the de novo pathway, was higher in SF tissue. Utilization of both uridine and uracil for nucleotide and nucleic acid synthesis clearly indicated that the salvage pathway of pyrimidine metabolism is also operative during shoot organogenesis. In general, uridine was a better substrate for the synthesis of salvage products than uracil, possibly due to the higher activity of uridine kinase (UK), compared to uracil phosphoribosyltransferase (UPRT). Incorporation of uridine into the nucleic acid fraction of OLD cotyledons was lower than that observed for their responsive (day 0) counterparts. Similarly, uracil utilization for nucleic acid synthesis was lower in NSF cotyledons, compared to that observed for SF tissue after 10 days in culture. This difference was ascribed to higher UPRT activity measured in the latter. Thus, there was an apparent difference in the utilization of nucleotides derived from uracil and uridine for nucleotide synthesis. The increased ability to produce pyrimidine nucleotides via the salvage pathway during shoot bud formation may be required in support of nucleic acid synthesis occurring during the process. Studies on thymidine metabolism confirmed this notion.

Benzyl Compounds↗

PubMed1996

Inhibition of transcription factor binding by ultraviolet-induced pyrimidine dimers.

The formation of DNA photoproducts by ultraviolet (UV) light is responsible for the induction of mutations and the development of skin cancer. Cis-syn cyclobutane pyrimidine dimers (pyrimidine dimers) are the most frequent lesions produced in DNA by UV irradiation. Besides being mutagenic, pyrimidine dimers may interfere with other important DNA-dependent processes. To analyze the effects of pyrimidine dimers on the ability of DNA sequences to be recognized by trans-acting factors, we have incorporated site-specific T-T dimers into oligonucleotides containing the recognition sequences of the sequence-specific transcription factors E2F, NF-Y, AP-1, NF kappa B, and p53. In each case, presence of the photodimer strongly inhibited binding of the respective transcription factor complex. Reduction of binding varied between 11- and 60-fold. The results indicate that the most common UV-induced DNA lesion can interfere severely with binding of several important cell cycle regulatory and DNA damage responsive transcription factors. We suggest that inhibition of transcription factor binding may be a major biological effect of UV radiation since promoter regions are known to be repaired inefficiently and since UV damage can deregulate the function of a large number of different factors.

Binding Sites↗

PubMed1950

Purine and pyrimidine contents of some desoxypentose nucleic acids.

The distribution of purines and pyrimidines in desoxypentose nucleic acids prepared from a variety of animal and plant sources has been studied. 1. The nucleic acids were prepared from calf thymus, calf kidney, sheep spleen, horse spleen, chicken erythrocyte, turtle erythrocyte, trout sperm, shad testes, sea urchin sperm, wheat germ, and Pneumococcus Type III. 2. Separate hydrolyses were carried out for the determination of purines and pyrimidines. These procedures permitted nearly quantitative recovery of nucleic acid phosphorus in many of the preparations examined. 3. In the case of those preparations where a quantitative recovery was obtained it can be concluded that no bases other than adenine, guanine, thymine, and cytosine were present in appreciable amounts. 4. The distribution of purines and pyrimidines in all the nucleic acids studied renders the tetranucleotide hypothesis untenable. 5. The results of the analyses have indicated no great differences in the composition of these nucleic acids with respect to purines and pyrimidines.

Adenine↗

PubMed1980

Purine and pyrimidine metabolism in hereditary orotic aciduria: some unexpected effects of allopurinol.

Purine and pyrimidine metabolism have been investigated in the longest surviving case of hereditary orotic aciduria after 15 years of chronic uridine therapy. Several unusual features were recorded: 1. Although the uridine dosage (0.5 mmol/kg) was adequate to control an otherwise normal clinical status, orotic acid excretion was still excessive (in congruent 7 mmol/24 h). Urinary drug metabolites (uracil and uridine), however, accounted for less than 7% of the daily uridine dose, and no orotidine, or any abnormal pyrimidines or purines, were identified at any time. 2. Urinary uric acid excretion was high and plasma uric acid low, resulting in a clearance up to 4 times normal. This was attributed to the uricosuric effect of orotic acid. 3. In direct contrast to previous findings in gouty subjects and healthy male controls we noted: (i) no increase in plasma or urinary uric acid levels, or uric acid clearance, following the change from a low to a high nucleoprotein regime (normally up to two-fold); (ii) allopurinol reduced both urinary uric acid and total oxypurine levels by more than 50% on the low (normally unaffected) as well as the high (normally reduced 20-50%) nucleoprotein regime; (iii) a substantial (up to 70%) reduction in orotic acid excretion during allopurinol therapy (normally mild orotic aciduria), of similar magnitude and in parallel with the reduction in uric acid levels. Uric acid and orotic acid excretion were closely related throughout. These findings differ from those of a similar study of hereditary orotic aciduria and suggest there is competitive transport between exogenous (dietary) purines and pyrimidines, as well as an important interdependence between endogenous purine and pyrimidine metabolism, by mechanisms as yet undefined.

Adolescent↗