Disease relevance of thiamine monophosphate

• Newly developed assays for FdUMP and dUMP were utilized to assess the competitive roles played by these nucleotides in determining the inhibition of TMP synthesis in mice bearing the P1534 ascites tumor [1].
• The chemical synthesis of new compounds designed as inhibitors of Mycobacterium tuberculosis TMP kinase (TMPK) is reported [2].
• Characterization of thiL, encoding thiamin-monophosphate kinase, in Salmonella typhimurium [3].
• CONCLUSIONS: The native form of the SIVagm TMP is a full-length gp40, similar to the SIV macaque (SIVmac) strain and HIV-1 [4].
• RESULTS: Five out of 31 (16%) patients developed hypersensitivity to TMP, and two ceased TMP as a result [5].

High impact information on thiamine monophosphate

• Thus, TMP, a member of a novel family of membrane glycoproteins with a suggested role in cellular contact, is a c-Myc target and is possibly involved in c-Myc-induced transformation [6].
• Compared with age-matched control subjects, type 1 diabetic patients presented significantly higher numbers of platelet and endothelial microparticles (PMP and EMP), total annexin V-positive blood cell microparticles (TMP), and increased levels of TMP-associated procoagulant activity [7].
• It is concluded that the single tightly bound Mn2+ on Pol I and a weakly bound Mn2+ which is tightened 100-fold by TMP are at the 3',5'-exonuclease active site and are essential for 3',5'-exonuclease activity, but not for polymerase activity [8].
• 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 [9].
• In order to investigate the functional significance of the TMP multigene family, which assures the synthesis of a mixture of related polypeptides, we have designed synthetic genes for heterologous expression of three different mature polypeptides, which were used to obtain sequence-specific rabbit antisera [10].

Chemical compound and disease context of thiamine monophosphate

• OBJECTIVE: We compared the efficacies of low-dose trimethoprim-sulphamethoxazole (TMP-SMX; one tablet: TMP, 160 mg, SMX, 800 mg, twice daily, twice a week) and aerosolized pentamidine (300 mg every 4 weeks) as secondary prophylaxis against Pneumocystis carinii pneumonia (PCP) in patients with HIV infection [11].
• The fidelity of DNA synthesis by reverse transcriptases from human immunodeficiency virus and other retroviruses was compared by measuring the rates of misincorporation of dCMP in the place of TMP in cell-free DNA synthesis with polyadenylic acid as the template [12].
• These data suggest that RFC1 may be one of the alternative transport routes available for TMP in some tissues when THTR-1 is mutated in the autosomal recessive disorder thiamine-responsive megaloblastic anemia [13].
• Responses of those treated with TMP/SMX and of those with susceptible Shigella treated with ampicillin were comparable [14].
• Norfloxacin (NOR) or cotrimoxazole (TMP/SMX) were randomly administered to 59 granulocytopenic patients with acute leukemia for prevention of bacterial infections [15].

Biological context of thiamine monophosphate

• We have isolated and characterized the thiL gene of S. typhimurium and showed that thiL is a 978-base pair open reading frame encoding a 35-kDa protein with thiamin-monophosphate kinase activity. thiL was located in the 10-centisome region of the S. typhimurium chromosome [3].
• Examination of mutant trichocysts created by targeted gene silencing of different TMP genes showed that the layer containing the products of the silenced genes is specifically affected, as are all subsequently assembled parts of the structure, consistent with an ordered assembly pathway [10].
• We present a model for trichocyst biogenesis in which TMP assembly is controlled by protein processing [10].
• TMP and centrin multigene families, previously studied in the macronuclear genome, consist of genes that are co-expressed to provide mixtures of related polypeptides that co-assemble to form respectively the crystalline trichocyst matrix and the infraciliary lattice, a contractile cytoskeletal network [16].
• RESULTS: PBMC of the naturally infected AGM contained a 'swarm' of related virus genotypes that encoded a full-length TMP, whereas tissue-culture passage in rhesus PBMC resulted in a prematurely truncated form of the TMP [4].

Anatomical context of thiamine monophosphate

• We present evidence that TMP and centrin genes identified in the macronucleus are also present in the micronucleus, ruling out the possibility that these novel multigene families are generated by somatic rearrangements during macronuclear development [16].
• Frozen sections of urogenital ridges from 14 1/2- to 17 1/2-day rat fetuses (n = 77) were incubated with a-naphthyl thymidine-5'-phosphate (naphthyl TMP) and Fast Red TR [17].
• A sensitive and specific assay was developed for liberation of intracellular TMP in cultured mouse L fibroblasts in which synthesis of TMP and, hence, of DNA was suppressed by a combination of aminopterin and 5'-amino-5'-deoxythymidine (5'-NH2-dT) [18].
• If TMP is assumed to enter solely by passive diffusion, the inactivity of the TMP derivatives can be ascribed in part to their 2-fold higher molecular weight which can be expected to reduce flux through natural membranes ca. 16-fold [18].
• However, photosensitive animals are affected differently from nonphotosensitive animals, as their content of TMP in the cerebral cortex increases on stimulation [19].

Associations of thiamine monophosphate with other chemical compounds

• Using site-directed mutagenesis to construct a mutant RNA template yielding a primer with the sequence 5'-GTAC-3', we demonstrated that FIAU-TP inhibited the incorporation of TMP, had no effect on that of dAMP, and decreased markedly the incorporation of dCMP [20].
• However, only the difference in TMP/GFR remained significant after adjustment for covariance attributable to serum calcium concentration, age, and creatinine clearance [21].
• In CSF of patients with ALS, however, thiamin monophosphate values decreased much more than thiamin levels, so that the T/TMP ratio was significantly increased [22].
• Of the 32P representing nucleoside aldehyde in DNA from NCS-exposed cells, 77% is in TMP; the rest is in AMP much greater than CMP greater than GMP, a distribution in excellent agreement with that obtained for in vitro drug-treated DNA [23].
• DNA polymerases alpha and delta from rabbit bone marrow were purified to specific activities greater than 30 000 nM TMP incorporated (mg of protein)(-1)h(-1). alpha is quantitatively predominant. alpha and delta have the same reaction requirements and are both similarly sensitive to N-ethylmaleimide [24].

Gene context of thiamine monophosphate

• In general, the nonclassical compounds 7-17 were similar in potency to TMP against Toxoplasma gondii DHFR, with selectivity ratios greater than 38 and 21 for 11 and 16, respectively [25].
• Inactivation of SHM1, SHM2 and ADE3 is required to render yeast auxotrophic for TMP and methionine, suggesting that TMP synthesized in mitochondria may be available to the cytoplasmic compartment [26].
• The results suggest an inverse pattern of expression for the two homologs, TMP expression being high during cell proliferation and PMP22 expression being high during growth arrest [27].
• The orf tmp is proposed to function as a tape measure protein, TMP, important for assembly of the TP901-1 phage tail and involved in tail length determination [28].
• DNA increased virus antigen-induced immune cell secretion of IFN-gamma only, whereas dUMP significantly increased secretion of IL-10 only. dGMP completely inhibited virus-triggered IFN-gamma secretion, whereas TMP did not change the virus induced secretion pattern of measured cytokines [29].

Analytical, diagnostic and therapeutic context of thiamine monophosphate

• Consistent with these sequence analyses, purified L. pifanoi P-4 protein possesses single strand nuclease (DNA and RNA) and phosphomonoesterase activity, with a preference for UMP > TMP > AMP >> CMP [30].
• This study aimed to characterize the topography and mechanism of slow EEG potentials related to tongue movement (TMP), and to devise a method for their elimination [31].
• Irradiation of dTpdT with 300 kJ/m2 of 254 nm produces numerous photo-products, one of which labeled dT6pd4T[1] was purified by HPLC. dT6pd4T has a UV spectrum (H20, pH 7) with lambda max = 326 nm and lambda min = 265 nm, and a P-31 NMR resonance at -3.46 ppm (normal dTpdT occurs at -4.01 ppm; TMP, 30 degrees C) [32].
• Treatment of mouse cell cultures with 5 X 10(-6)M trioxalen (4,5',8-trimethylpsoralen, or TMP) followed by long wavelength ("near") UV-irradiation (NUV) resulted in immediate cessation of most of the cellular transcriptional activity [33].
• We therefore prospectively randomized 58 cardiac transplant recipients to receive TMP (160 mg)-SMX (800 mg) twice daily either three days per week (group B), or seven days per week (group C), or to receive no treatment (group A) [34].

References