Methotrexate

30 Mar

Methotrexate
metalloenzyme a protein combined with one or more metal atoms that functions as an enzyme. metalloprotein any protein that requires at least one metal ion for normal functioning. For example, mammalian cytochrome c oxidase is a key enzyme in aerobic metabolism, containing six metal centers (two hemes, two copper centers, Mg, and Zn). The simplest known Mo enzyme (containing molybde- num) is dimethyl sulfoxide (DMSO) reductase of Rhodobacter spheroides, which catalyzes the conver- sion of DMSO to dimethyl sulfide. See androgen re- ceptor, ceruloplasmin, metalloenzyme, RING finger, urease, vitamin D receptor, Wilms tumor, Wilson dis- ease, zinc finger proteins. metallothioneins small proteins that bind heavy metals and thereby protect cells against their toxic effects.

Genes coding for metallothioneins are acti- vated by the same metal ions that these proteins bind. metamale in Drosophila, a poorly viable male char- acterized by cells containing one X and three sets of autosomes; previously called a supermale. See inter- sex, metafemale. metamerism the serial segmentation of an ani- mal’s body along its anterior-posterior axis. A milli- pede is an example of this kind of organization. The repeated segments are sometimes called metamers or somites. Metamerism can also occur along the axes of appendages produced by metamers. Metamerism is common in annelids, arthropods, and chordates. See homeotic mutations, segment identity genes, se- lector genes, zygotic segmentation mutants. metamorphosis the transformation from larval to adult form. In Drosophila the destruction of larval tissues and their replacement with adult ones is trig- gered by 20-hydroxy-ecdysone.

See ecdysones. metaphase See mitosis. metaphase arrest referring to the accumulation of metaphase figures in a population of cells poisoned with colchicine, Colcemid, or some other spindle poison. metaphase plate the grouping of the chromo- somes in a plane at the equator of the spindle during the metaphase stage of mitosis (q.v.). metastable state an excited state of an atomic nu- cleus, which returns to its ground state by the emis- sion of radiation. metastasis the spread of malignant neoplastic cells from the original site to another part of the body. metatarsus the basal tarsal segment of the insect leg. In the male of Drosophila melanogaster, the metatarsus of each foreleg bears a sex comb. metathorax the hindmost of the three thoracic segments of an insect. It bears a pair of legs and (in many winged insects) a pair of wings. In flies, it bears the halteres. Methanococcus jannaschii an anaerobic metha- nogen that lives at high temperatures and extreme pressures in geothermal marine sediments. This archaeon is a chemolithoautotroph gains its energy by the reaction 4H2 + CO2 → CH4 + 2H2O. Its chromosome is a circular DNA molecule made up of 1,644,976 base pairs that contain 1,682 ORFs. It also has two additional genetic elements.

The larger is a circle made up of 58,407 bps that contain 44 ORFs, and the smaller circle is made up of 16,550 bps containing 12 ORFs. The genomes of M. jannaschii and H. influenzae are about the same size, yet they differ in the number of genes of un- known functions that they contain. The bacterium Haemophilus has 22% URFs, while the archaeon Methanoccus has 62% URFs. Methanococcal genes devoted to transcription, translation, and replication resemble those of eukaryotes more closely than bac- teria. See Appendix A, Archea, Euryarchaeota; Ap- pendix C, 1996, Bult et al.; Appendix E; Archaebacte- ria, Archaeoglobus fulgidus, hyperthermophile. methanogens prokaryotes that belong to the phy- lum Euryarcheota of the Archaea (see Appendix A). They live in oxygen-free environments and generate methane by the reduction of carbon dioxide. See Methanococcus jannaschii. methionine the molecule that is the leading amino acid in a newly formed protein. In many proteins this is subsequently removed by an aminopeptidase and, as a result, the second amino acid becomes N terminal. It follows that in eukaryotes the methio- nine-specifying codon (AUG) is recognized by dif- ferent specific tRNAs, depending on whether it is at the start of the mRNA or at an internal position.

See amino acid, initiator tRNA. method of least squares See least squares. methotrexate a folic acid antagonist that kills cells by inhibiting the enzyme dihydrofolate reductase and thus blocking the synthesis of nucleic acids. Mammalian cells that develop resistance to metho- trexate do so by amplifying the genes encoding dihy- drofolate reductase. See Appendix C, 1978, Schimke et al.; folic acid.

Methuselah
methuselah a gene in Drosophila that when mu- tated increases longevity. Normal flies live about 60 days on the average, whereas methuselah mutants last 80 days. See Appendix C, 1998, Lin, Serounde, and Benzer. Compare with progeria. methyladenine See 5-methylcytosine. methylated cap a modified guanine nucleotide terminating eukaryotic mRNA molecules. The cap is introduced after transcription by linking the 5′ end of a guanine nucleotide to the 5′ terminal base of the mRNA and adding a methyl group to position 7 of this terminal guanine. The addition of the termi- nal guanine is catalyzed by the enzyme guanylyl transferase.

Another enzyme, guanine-7-methyl trans- ferase, adds a methyl group to the 7 position of the terminal guanine. Unicellular eukaryotes have a cap with this single methyl group (cap 0). The predomi- nant form of the cap in muticellular eukaryotes (cap 1) has another methyl group added to the next base at the 2′-o position by the enzyme 2′-o-methyl trans- ferase. More rarely, a methyl group is also added to the 2′-o position of the third base, creating cap 2 type. Capping occurs shortly after the initiation of transcription and precedes all excision and splicing events. The function of the cap is not known, bu it may protect the mRNA from degradation by nucleases or provide a ribosome binding site. See posttranscriptional processing. methylation of nucleic acids the addition of a methyl group (−CH3) to DNA. See DNA methyla- tion, restriction and modification model, parental im- printing. methylcholanthrene a carcinogenic hydrocarbon.

5-methylcytosine (5-mCyt) a modified base found in the DNA of both prokaryotes and eukaryotes. Only 5-mCyt is found in plants and animals, but prokaryotes also contain N6-methyladenine in their DNA. 5-mCyt is generated by a specific methyl transferase (q.v.), which transfers an activated methyl group from a donor molecule (S-adenosylmethio- nine) to specific cytosines in DNA. In mammalian chromosomes, the bulk of 5-mCyt is in simple se- quence repetitive DNAs, but it is also present throughout all sequences. In E. coli and its viruses, specific genes contain methylated cytosines. This modified pyrimidine undergoes spontaneous deami- nation that converts 5-methylcytosine to thymine. Thus, base substitutions occur at elevated rates in these regions and are responsible for mutational hot spots (q.v.). See Appendix C, 1961, Benzer; 1978, Coulondre et al.; DNA methylation. methyl green a basic dye that can detect DNA. In 2 molar solution of magnesium chloride at pH 5.7 methyl green stains only undegraded DNA. See pyr- onin Y.

methyl guanosine See rare bases. methyl inosine See rare bases. methyl transferase an enzyme that adds a methyl group to a purine or pyrimidine. Methyl groups are commonly added to guanine or cytosine molecules. As shown on page 275, a fully methylated segment of DNA becomes hemimethylated upon replication. So for a methylated site to be transmitted through a series of mitotic cycles, a mechanism must exist that ensures that methyl transferases recognize hemi- methylated sites and convert them to full methyla- tion. See Appendix E; Achilles’ heel cleavage, bases of nucleic acids, DNA methylation, methylated cap, 5- methylcytosine, parental imprinting, posttranslational processing, restriction, and modification model, te- lomeric silencing. metric traits See quantitative character, continu- ous variation. METRO message transport organizer (q.v.). Mg magnesium. MHC major histocompatibility complex (q.v.). MIC major immunogene complex (q.v.).

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