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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of phenytoin (DPH) on folate metabolism have been studied in female Swiss Webster mice. Doses of DPH which produce steady-state plasma levels of DPH in the therapeutic range of 10-20 micrograms/ml were found to decrease plasma folate levels. In addition, the in vivo oxidation rate of [14C] formate and [2-14C] histidine to 14CO2 was increased. The increased metabolic rates were accompanied by a decrease in the hepatic activity of N5, N10-methylenetetrahydrofolate (5, 10-CH2-H4folate) reductase. N5-methyltetrahydrofolate-homocysteine transmethylase (methionine synthase); EC 2.1.1.13) activity in the liver was unchanged. The distribution of folates in the liver was determined by high-pressure liquid chromatography (HPLC) and it was found that the concentration of tetrahydrofolate (H4folate) was increased in DPH-treated mice whereas the concentration of N5-methyltetrahydrofolate was decreased. These effects were observed in mice treated with DPH for 4 days, but not in mice given a single DPH injection 24 hr previously. Decreased activity of hepatic 5, 10-CH2-H4folate reductase is postulated to account for the other effects which were observed. Decreased activity presumably results in increased tissue concentrations of 5, 10-CH2-H4folate, which is in equilibrium with its dissociation products, H4folate and formaldehyde. Increased concentrations of H4folate lead to increases in the oxidation rate of formate and histidine. These effects on folate metabolism may have important implications in the pharmacological and toxicological effects of DPH.
Mol Pharmacol 1984 May
PMID:Decreased hepatic 5, 10-methylenetetrahydrofolate reductase activity in mice after chronic phenytoin treatment. 637 25

The source of the oxygen atom in the product of the cytochrome P-450-catalyzed N-demethylation of N-methylcarbazole was determined by mass spectral analysis of the carbinolamine precursor of formaldehyde formed during incubation in oxygen 18-enriched medium. Initial experiments demonstrated that N-(hydroxymethyl)carbazole, the carbinolamine product of the metabolism of N-methylcarbazole, did not exchange oxygen with solvent water. When N-methylcarbazole was incubated in oxygen 18-enriched medium with purified cytochrome P-450 in the presence of either purified NADPH-cytochrome P-450 reductase and NADPH, cumene hydroperoxide, t-butyl hydroperoxide, or peracetic acid, there was no incorporation of oxygen 18 from the medium into N-(hydroxymethyl)carbazole. These results clearly demonstrate that the oxygen atom inserted into N-methylcarbazole by cytochrome P-450 to yield N-(hydroxymethyl)carbazole does not come from the medium and show that the N-demethylation reactions catalyzed by cytochrome P-450 proceed in a manner similar to hydroxylation reactions, with the oxygen atom in the product being derived from the oxidant.
Mol Pharmacol 1983 May
PMID:Source of the oxygen atom in the product of cytochrome P-450-catalyzed N-demethylation reactions. 640 92

Chromosomal proteins were treated with imido esters or with formaldehyde. Histones and their oligomers were then obtained by acid extraction and analyzed by two-dimensional gel electrophoresis. We discovered a nonameric histone oligomer in which histone H1 complexes with the octamer of small histones. In this complex, H1 interacts preferentially with H2a and H3. One can suppose from these experiments that histone H1 has close contacts with core histones. Another conclusion from the results obtained is that the structure of the nucleosome core is different in H1-containing mononucleosomes and in core particles. Thus, histone H1 is an important component of the nucleosomal protein complex and its presence is necessary for supporting the native compact state of the nucleosomal core.
Mol Biol (Mosk)
PMID:[Structure of chromosomal deoxyribonucleoproteins. X. Investigation of protein organization in chromosomal subunits with the aid of bifunctional agents]. 645 9

Peculiarities of reversible interaction of formaldehyde with DNA, adenine and some cytosine derivatives in the presence of primary or secondary amines have been studied. Different characters of the examined formaldehyde reactions have been demonstrated. Thus, melting of DNA by formaldehyde at neutral pH is accelerated only in the presence of primary amines. Using UV-spectra data analysis it was concluded that products of cytidine and adenine modification by formaldehyde or methylol derivatives of secondary amines have similar structure. Cytidine and adenine modifications when treated with formaldehyde and primary amine mixture were considerably different and resulted in products with different structures. This is probably related to interactions within two positions of cytosine or adenine residues. A hypothetical scheme of formation and structure of modification products are considered.
Mol Biol (Mosk)
PMID:[Characteristics of formaldehyde reactions with nucleic acids and their structural components in the presence of primary or secondary amines]. 665 58

Upon infection, the Newcastle disease virus (NDV) genome is transcribed to produce 18S, 22S, and 35S RNAs (M. Bratt , and W. Robinson, J. Mol. Biol. 23:1-21, 1967). The 22S RNA has been shown to contain 18S sequences and is thought to represent polycistronic transcripts generated by transcriptional readthrough of adjacent genes ( Varich et al., Acta Virol. 23:341-343, 1979). With improved extraction procedures, the 22S RNA was found to represent up to 25% of the total transcription in NDV-infected cells. This RNA was resolved into at least five discrete species on formaldehyde-agarose gels. All but one of these molecules contain 3' polyadenylate sequences but not internal polyadenylate sequences. These transcripts are found on polyribosomes of infected cells, suggesting that they are functional mRNAs.
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PMID:Structural and functional characterization of Newcastle disease virus polycistronic RNA species. 672 96

Six recessive second chromosomal mutants of Drosophila melanogaster exhibiting larval hypersensitivity to methyl methanesulfonate have been identified and assigned to six complementation groups. The strains have been analyzed for their sensitivities to UV, X-ray, nitrogen mustard and formaldehyde. Two classes of mutants not previously observed in Drosophila have been identified. The mus 204A1 and mus 205A1 mutants exhibit sensitivity to MMS and UV but not X-ray or nitrogen mustard, while the mus 206A1 and mus 207A1 mutants display sensitivity to MMS, UV, and nitrogen mustard. Four of the seven strains exhibit poor female fertility and two of these are shown to have a weak meiotic disjunctional defect. Biochemical studies of the mus 205A1 mutant suggest a defect in DNA synthetic ability associated with excision and postreplication repair performed on UV and alkylation-damaged templates (Boyd and Harris 1981; Brown and Boyd 1981 b; R.L. Dusenbery, manuscript in preparation).
Mol Gen Genet 1982
PMID:Mutagen sensitivity of Drosophila melanogaster. V. Identification of second chromosomal mutagen sensitive strains. 681 27

We have analyzed the differential expression of a family of beta-like globin genes during the development of rabbits, from four days post implantation to one week before birth. The family is composed of four genes, arranged 5'-beta 4-beta 3-psi beta 2-beta 1-3' on the chromosome; psi beta 2 is an inactive pseudogene. Using the technique of hybrid-arrested translation in vitro, we have identified the embryo-specific globin polypeptides encoded by genes beta 3 and beta 4. The beta 3 and beta 4 globins are replaced by the adult beta 1 globin halfway through gestation; this corresponds temporally with the switch in site of erythropoiesis from the embryonic yolk sac to the fetal liver. The decline in production of beta 3 globin polypeptide precedes the decline in beta 4 globin. Transcripts from genes beta 1, beta 3 and beta 4 were analyzed at progressive stages of gestation by a blot-hybridization assay and by an S1 nuclease protection assay. Mature messenger RNA and presumptive precursor RNAs from genes beta 3 and beta 4 are synthesized abundantly in embryonic erythroid cells but only at very low levels later in fetal development. Conversely, precursor and mature mRNA from gene beta 1 are found at very low levels in embryos but are abundant in fetal and adult erythroid cells. The co-ordinate appearance of precursor RNA, mRNA and polypeptide from all three active genes indicates that the primary developmental regulation of this gene family is exerted at the level of transcription. RNA species larger than the expected precursors were observed when the RNA was denatured with formaldehyde but not when methylmercury was the denaturant. These large RNAs are a formaldehyde-generated artifact, possibly a result of cross-linking globin transcripts to ribosomal RNA. We observe no extensive stable transcripts from the 5' or 3' flanking regions of these genes.
J Mol Biol 1983 Mar 05
PMID:Analysis of rabbit beta-like globin gene transcripts during development. 684 97

The avaliable data on equilibrium fluctuations in DNA are critically analyzed. Fluctuations of these types are considered: bending and torsional fluctuations and fluctuational opening of base pairs. The latest experimental and theoretical work has made it possible to estimate the bending and torsional stiffnesses of the double helix. Either of these stiffnesses has been determined by at least two different methods that have led to the same results. The stiffness of the double helix is definitely shown to be independent of the concentration of counterions when it exceeds 10(-2) M Na+. As to the fluctuational opening, the current literature is controversial and different methods lead to contradictory results. The method based on DNA unwinding by formaldehyde is considered in some detail. Strong evidence is presented in favour of the modification of base pairs without their complete opening, through an "outside" reaction. Incorporation of this modification route into the theoretical model of DNA unwinding eliminates the last descrepancies between theory and experiment. The successful accounting for all details of the process of DNA unwinding by formaldehyde is argued to prove the adequacy of the helix-coil transition theory as a basis for describing the process of base-pairs opening. The conclusion of McGhee and von Hippel, who obtained a highly overestimated value of the base-pair opening probability proceeding from the formaldehyde kinetics, is shown to be based on an erroneous assumption. The NMR data of Early et al. are briefly discussed. They strongly support the author's concept. A critical comment is made concerning the interpretation of the hydrogen exchange data by Mandel, Kallenbach and Englander. The highly overestimated value of the probability of base-pair opening claimed by these authors is most probably based on unjustified assumptions.
Mol Biol (Mosk)
PMID:[Fluctuational mobility of DNA]. 687 35

Alterations in membrane fluidity caused by alcohols and tetrahydro-beta-carbolines (THBCs) have been studied. Dipalmitoylphosphatidylcholine vesicles were used as a membrane preparation, and changes in the fluidity were revealed by two fluorescent probes: 1-anilinonaphthalene-8-sulfonic acid (1,8-ANS) and N-phenylnaphthylamine (NPN). It was found that THBCs, which are condensation products of tryptamine and formaldehyde or acetaldehyde, were at least 2 orders of magnitude more potent in causing fluidity changes than the comparable alcohols (methanol and ethanol). Both 1,8-ANS (binding close to the polar end of the phospholipid molecules) and NPN (binding to the hydrophobic region of the membrane) were able to reveal changes in membrane fluidity, although there were differences between the behavior of the two probes. The condensation product of acetaldehyde--the primary metabolite of ethanol--and tryptamine were found to be 200-300 times more potent in causing fluidity changes than ethanol itself (as determined with both 1,8-ANS and NPN).
Mol Pharmacol 1982 Nov
PMID:Increased fluidity of a model membrane caused by tetrahydro-beta-carbolines. 689 59

The secondary structure of myoglobin, treated with formaldehyde, has been studied by absorption spectroscopy, circular dichroism and gel-chromatography. The chemical modification of protein leads to disturbance of the polypeptide alpha-helix and destruction of the heme environment. The unfolding of protein in the presence of formaldehyde is a reversible process, the rate of transition is conditioned by temperature and formaldehyde concentration. At certain temperature conditions and formaldehyde concentration it is possible to obtain completely unfolded protein. The denaturation of myoglobin in the presence of formaldehyde is not cooperative in contrast to classical denaturation by pH, temperature, urea and other agents. Presence of some aminoacids causes inhibition of conformational changes in the protein molecule. Possible mechanisms of denaturation of myoglobin in the presence of formaldehyde are discussed.
Mol Biol (Mosk)
PMID:[Induction by formaldehyde of conformational changes from helix to globule in the myoglobin molecule]. 692 56


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