機序に基づく抑制

WordNet

any of various water-soluble compounds capable of turning litmus blue and reacting with an acid to form a salt and water; "bases include oxides and hydroxides of metals and ammonia" (同)alkali
(numeration system) the positive integer that is equivalent to one in the next higher counting place; "10 is the radix of the decimal system" (同)radix
the bottom side of a geometric figure from which the altitude can be constructed; "the base of the triangle"
situate as a center of operations; "we will base this project in the new lab"
a place that the runner must touch before scoring; "he scrambled to get back to the bag" (同)bag
installation from which a military force initiates operations; "the attack wiped out our forward bases" (同)base of operations
a support or foundation; "the base of the lamp" (同)pedestal, stand
(electronics) the part of a transistor that separates the emitter from the collector
a flat bottom on which something is intended to sit; "a tub should sit on its own base"
the principal ingredient of a mixture; "glycerinated gelatin is used as a base for many ointments"; "he told the painter that he wanted a yellow base with just a hint of green"; "everything she cooked seemed to have rice as the base"
the place where you are stationed and from which missions start and end (同)home
(anatomy) the part of an organ nearest its point of attachment; "the base of the skull"
the bottom or lowest part; "the base of the mountain"
illegitimate (同)baseborn
of low birth or station (`base is archaic in this sense); "baseborn wretches with dirty faces"; "of humble (or lowly) birth" (同)baseborn, humble, lowly
not adhering to ethical or moral principles; "base and unpatriotic motives"; "a base, degrading way of life"; "cheating is dishonorable"; "they considered colonialism immoral"; "unethical practices in handling public funds" (同)immoral
having or showing an ignoble lack of honor or morality; "that liberal obedience without which your army would be a base rabble"- Edmund Burke; "taking a mean advantage"; "chokd with ambition of the meaner sort"- Shakespeare; "something essentially vulgar and meanspirited in politics" (同)mean, meanspirited
(used of metals) consisting of or alloyed with inferior metal; "base coins of aluminum"; "a base metal"
debased; not genuine; "an attempt to eliminate the base coinage"
the atomic process that occurs during a chemical reaction; "he determined unique mechanisms for the photochemical reactions" (同)chemical mechanism
the technical aspects of doing something; "a mechanism of social control"; "mechanisms of communication"; "the mechanics of prose style" (同)mechanics
device consisting of a piece of machinery; has moving parts that perform some function
(philosophy) the philosophical theory that all phenomena can be explained in terms of physical or biological causes
a natural object resembling a machine in structure or function; "the mechanism of the ear"; "the mechanism of infection"
(physiology) the process whereby nerves can retard or prevent the functioning of an organ or part; "the inhibition of the heart by the vagus nerve"
(psychology) the conscious exclusion of unacceptable thoughts or desires (同)suppression
the quality of being inhibited
having a base; "firmly based ice"
having a base of operations (often used as a combining form); "a locally based business"; "an Atlanta-based company"; "carrier-based planes"

PrepTutorEJDIC

《文》(人や人の行動・孝えが)『卑しい』,下劣な / (金属が)質の劣った;(貨幣が)粗悪な
『基礎』,根拠 / 『基部』,基底,土台 / 『根拠地』,基地 / (野球の)塁,ベース / 主成分;塩基(酸と反応シテ塩(官)を生じる化合物) / (数学で図形の)底;底辺;基線 / (…に)…‘の'『基礎をおく』《+『名』+『on』(『upon』)+『名』》
〈C〉機械;(部分的な)機械装置 / 〈C〉(機械装置に似た)機構 / 〈C〉(物事が行われる)仕組み,方法 / 〈U〉機械論
禁止; 抑制; （心理学で）抑制; （化学で）（反応の）阻害, 抑制

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/01/15 04:59:50」(JST)

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In biochemistry, suicide inhibition, also known as suicide inactivation or mechanism-based inhibition, is an irreversible form of enzyme inhibition that occurs when an enzyme binds a substrate analogue and forms an irreversible complex with it through a covalent bond during the "normal" catalysis reaction. The inhibitor binds to the active site where it is modified by the enzyme to produce a reactive group that reacts irreversibly to form a stable inhibitor-enzyme complex. This usually uses a prosthetic group or a coenzyme, forming electrophilic alpha and beta unsaturated carbonyl compounds and imines.

Examples

Some clinical examples of suicide inhibitors include:

Aspirin, which inhibits cyclooxygenase 1 and 2 enzymes.
Penicillin, which inhibits DD-transpeptidase from building bacterial cell walls.
Sulbactam, which prohibits penicillin-resistant strains of bacteria from metabolizing penicillin.
Allopurinol, which inhibits uric acid production by xanthine oxidase in the treatment of gout.
AZT (zidovudine) and other chain-terminating nucleoside analogues used to inhibit HIV-1 reverse transcriptase in the treatment of HIV/AIDS.
Eflornithine, one of the drugs used to treat sleeping sickness, is a suicide inhibitor of ornithine decarboxylase.
Sarin is a suicide inhibitor of acetylcholinesterase.
5-fluorouracil acts as a suicide inhibitor of thymidylate synthase during the synthesis of thymine from uridine. This reaction is crucial for the proliferation of cells, particularly those that are rapidly proliferating (such as fast-growing cancer tumors). By inhibiting this step, cells die from a thymineless death because they have no thymine to create more DNA. This is often used in combination with Methotrexate, a potent inhibitor of dihydrofolate reductase enzyme.
Exemestane, a drug used in the treatment of breast cancer, is an inhibitor of the aromatase enzyme.
Selegiline,^[1] although in the attached reference the compound is called a 'suicide inactivator' (not inhibitor).
Vigabatrin, an anticonvulsant, is a suicide inhibitor of GABA-T.

Rational drug design

Suicide inhibitors are used in what is called "rational drug design" where the aim is to create a novel substrate, based on already known mechanisms and substrates. The main goal of this approach is to create substrates that are unreactive until within that enzyme's active site and at the same time being highly specific. Drugs based on this approach have the advantage of very few resulting side effects.

References

^ Fowler, Joanna S. (1977). "2-Methyl-3-butyn-2-ol as an acetylene precursor in the Mannich reaction. A new synthesis of suicide inactivators of monoamine oxidase". The Journal of Organic Chemistry. 42 (15): 2637–7. doi:10.1021/jo00435a026. PMID 874623.

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English Journal

A dual function of the furanocoumarin chalepensin in inhibiting Cyp2a and inducing Cyp2b in mice: the protein stabilization and receptor-mediated activation.

Lo WS, Lim YP, Chen CC, Hsu CC, Souček P, Yun CH, Xie W, Ueng YF.SourceNational Research Institute of Chinese Medicine, No. 155-1, Li-Nong Street, Sec. 2, Taipei, 112, Taiwan, ROC.
Archives of toxicology.Arch Toxicol.2012 Dec;86(12):1927-38. doi: 10.1007/s00204-012-0902-7. Epub 2012 Jul 12.
Chalepensin, a furanocoumarin, is present in several medicinal Rutaceae plants and causes a mechanism-based inhibition of human and mouse cytochrome P450 (P450, CYP) 2A in vitro. To address the in vivo effect, we investigated the effects of chalepensin on multiple hepatic P450 enzymes in C57BL/6JNar
PMID 22790670

Inhibition of Bupropion Metabolism by Selegiline: Mechanism-Based Inactivation of Human CYP2B6 and Characterization of Glutathione and Peptide Adducts.

Sridar C, Kenaan C, Hollenberg PF.SourceDepartment of Pharmacology, The University of Michigan, 1150 West Medical Center Dr, Ann Arbor, MI 48109-5632. phollen@umich.edu.
Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2012 Dec;40(12):2256-66. doi: 10.1124/dmd.112.046979. Epub 2012 Aug 30.
Selegiline, the R-enantiomer of deprenyl, is used in the treatment of Parkinson's disease. Bupropion, an antidepressant, often used to treat patients in conjunction with selegiline, is metabolized primarily by CYP2B6. The effect of selegiline on the enzymatic activity of human cytochrome CYP2B6 in a
PMID 22936314

Japanese Journal

Glutathione-analogous peptidyl phosphorus esters as mechanism-based inhibitors of γ-glutamyl transpeptidase for probing cysteinyl-glycine binding site.