Lub luag haujlwm ntawm microsomal oxidation hauv lub neej ntawm cov kab mob yog qhov nyuaj rau overestimate lossis saib tsis taus. Inactivation ntawm xenobiotics (xws li tshuaj lom), kev tawg thiab tsim cov tshuaj hormones adrenal, kev koom tes hauv cov metabolism hauv cov protein thiab kev khaws cia ntawm cov ntaub ntawv ntawm caj ces tsuas yog ib feem me me ntawm cov teeb meem paub uas daws tau vim microsomal oxidation. Qhov no yog cov txheej txheem tswj hwm tus kheej hauv lub cev uas pib tom qab cov khoom ua rau nkag mus thiab xaus nrog kev tshem tawm.
Definition
Microsomal oxidation yog ib qho kev cuam tshuam ntawm cov tshuaj muaj nyob rau hauv thawj theem ntawm xenobiotic transformation. Lub ntsiab ntawm cov txheej txheem yog hydroxylation ntawm cov khoom siv oxygen atoms thiab tsim cov dej. Vim li no, cov qauv ntawm cov khoom qub hloov pauv, thiab nws cov khoom muaj peev xwm ua tau ob qho tib si thiab txhim kho.
Microsomal oxidation tso cai rau koj mus rau qhov kev sib txuas lus. Qhov no yog theem thib ob ntawm kev hloov pauv ntawm xenobiotics, thaum kawg ntawm cov molecules uas tsim tawm hauv lub cev yuav koom nrog pawg ua haujlwm uas twb muaj lawm. Qee zaum cov tshuaj nruab nrab yog tsim uas ua rau muaj kev puas tsuaj rau daim siab hlwb, necrosis thiab oncological degeneration ntawm cov ntaub so ntswg.
Oxidase yam oxidation
Microsomal oxidation cov tshuaj tiv thaiv tshwm sim sab nraum mitochondria, yog li lawv haus li kaum feem pua ntawm tag nrho cov pa oxygen nkag mus rau hauv lub cev. Lub ntsiab enzymes hauv cov txheej txheem no yog oxidases. Lawv cov qauv muaj cov atoms ntawm cov hlau uas muaj qhov sib txawv, xws li hlau, molybdenum, tooj liab thiab lwm yam, uas txhais tau hais tias lawv muaj peev xwm txais tau electrons. Nyob rau hauv lub cell, oxidases nyob rau hauv tshwj xeeb vesicles (peroxisomes) uas nyob rau ntawm lub txheej membrane ntawm mitochondria thiab nyob rau hauv lub ER (granular endoplasmic reticulum). Lub substrate, ntog ntawm peroxisomes, poob hydrogen molecules, uas txuas mus rau ib tug dej molecule thiab tsim peroxide.
Tsuas muaj tsib oxidases:
- monoaminooxygenase (MAO) - pab oxidize adrenaline thiab lwm yam biogenic amines tsim nyob rau hauv cov qog adrenal;
- diaminooxygenase (DAO) - koom nrog oxidation ntawm histamine (tus neeg nruab nrab ntawm kev mob thiab kev ua xua), polyamines thiab diamines;
- oxidase ntawm L-amino acids (uas yog, sab laug tes molecules);
- oxidase ntawm D-amino acids (txoj cai-rotating molecules);
- xanthine oxidase - oxidize adenine thiab guanine (nitrogenous bases suav nrog hauv DNA molecule).
Qhov tseem ceeb ntawm microsomal oxidation los ntawm hom oxidase yog tshem tawm xenobiotics thiab inactivate biologically active tshuaj. Kev tsim cov peroxide, uas muaj cov kab mob bactericidal thiab kev ntxuav txhua yam ntawm qhov chaw raug mob, yog ib qho kev mob tshwm sim uas nyob hauv qhov chaw tseem ceeb ntawm lwm cov teebmeem.
Oxygenase yam oxidation
Cov tshuaj tiv thaiv Oxygenase hauv lub cell kuj tshwm sim ntawm granular endoplasmic reticulum thiab ntawm cov plhaub sab nraud ntawm mitochondria. Qhov no yuav tsum muaj cov enzymes tshwj xeeb - oxygenases, uas txhawb nqa oxygen molecule los ntawm substrate thiab qhia nws mus rau hauv cov khoom oxidized. Yog tias ib qho oxygen atom tau qhia, ces lub enzyme hu ua monooxygenase lossis hydroxylase. Nyob rau hauv rooj plaub ntawm kev taw qhia ntawm ob atoms (uas yog, tag nrho cov molecule ntawm oxygen), lub enzyme hu ua dioxygenase.
Oxygenase-type oxidation cov tshuaj tiv thaiv yog ib feem ntawm peb lub ntsiab lus multi-enzyme complex, uas koom nrog kev hloov ntawm electrons thiab protons los ntawm substrate, ua raws li kev ua kom oxygen. Tag nrho cov txheej txheem no tshwm sim nrog kev koom tes ntawm cytochrome P450, uas yuav tau tham txog ntau yam ntxiv tom qab.
Piv txwv ntawm cov tshuaj tiv thaiv oxygenase
Raws li tau hais los saum toj no, monooxygenases tsuas yog siv ib qho ntawm ob qho muaj oxygen atoms rau oxidation. Qhov thib ob lawv txuas rau ob lub hydrogen molecules thiab tsim dej. Ib qho piv txwv ntawm xws li cov tshuaj tiv thaiv yog tsim ntawm collagen. Nyob rau hauv tas li ntawd, vitamin C ua raws li cov pa oxygen pub, Proline hydroxylase siv cov pa molecule los ntawm nws thiab muab nws rau proline, uas, nyob rau hauv lem, muaj nyob rau hauv lub procollagen molecule. Cov txheej txheem no muab lub zog thiab elasticity rau cov ntaub so ntswg sib txuas. Thaum lub cev tsis muaj vitamin C, gout tshwm sim. Nws yog tshwm sim los ntawm kev qaug zog ntawm cov ntaub so ntswg, los ntshav, bruising, hniav poob, uas yog, qhov zoo ntawm collagen nyob rau hauv lub cev ua.hauv qab no.
Lwm qhov piv txwv yog hydroxylases, uas hloov cov roj cholesterol molecules. Qhov no yog ib qho ntawm cov theem hauv kev tsim cov tshuaj steroid, nrog rau cov tshuaj hormones poj niam txiv neej.
qis tshwj xeeb hydroxylases
Cov no yog hydrolases xav tau los oxidize txawv teb chaws xws li xenobiotics. Lub ntsiab lus ntawm cov tshuaj tiv thaiv yog ua kom cov tshuaj no ntau tractable rau excretion, ntau soluble. Cov txheej txheem no hu ua detoxification thiab feem ntau tshwm sim hauv daim siab.
Vim suav nrog tag nrho cov molecule ntawm cov pa hauv xenobiotics, lub voj voog cov tshuaj tiv thaiv tau tawg thiab ib qho tshuaj nyuaj ua rau ntau yam yooj yim thiab siv tau ntau dua cov txheej txheem metabolic.
Reactive oxygen hom
Oxygen yog ib yam khoom uas muaj peev xwm txaus ntshai, vim qhov tseeb, oxidation yog txheej txheem combustion. Raws li ib tug molecule O2 los yog dej, nws yog ruaj khov thiab chemically inert vim nws cov hluav taws xob theem puv thiab tsis muaj electrons tshiab tuaj yeem txuas tau. Tab sis cov tebchaw uas oxygen tsis muaj ib khub ntawm tag nrho cov electrons yog reactive heev. Yog li ntawd, lawv hu ua active.
Cov pa oxygen zoo li no:
- Hauv cov tshuaj tiv thaiv monoxide, superoxide yog tsim, uas yog cais los ntawm cytochrome P450.
- Hauv cov tshuaj tiv thaiv oxidase, tsim cov peroxide anion (hydrogen peroxide) tshwm sim.
- Nyob rau hauv reoxygenation ntawm cov ntaub so ntswg uas tau undergone ischemia.
Tus neeg sawv cev oxidizing muaj zog tshaj plaws yog hydroxyl radical, nwsmuaj nyob rau hauv daim ntawv dawb xwb rau ib lab ntawm ib tug thib ob, tab sis lub sij hawm no ntau oxidative tshua muaj sij hawm mus txog. Nws qhov peculiarity yog tias hydroxyl radical ua rau cov tshuaj tsuas yog nyob rau hauv qhov chaw uas nws tau tsim, vim nws tsis tuaj yeem nkag mus rau cov ntaub so ntswg.
Superoxidanion thiab hydrogen peroxide
Cov tshuaj no muaj zog tsis yog ntawm qhov chaw tsim, tab sis kuj nyob ntawm qee qhov deb ntawm lawv, vim tias lawv tuaj yeem nkag mus rau hauv cov cell membranes.
Hydroxy pawg ua rau oxidation ntawm amino acid residues: histidine, cysteine thiab tryptophan. Qhov no ua rau inactivation ntawm enzyme systems, nrog rau kev cuam tshuam ntawm kev thauj cov proteins. Tsis tas li ntawd, microsomal oxidation ntawm cov amino acids ua rau kev puas tsuaj ntawm cov qauv ntawm nucleic nitrogenous bases thiab, raws li qhov tshwm sim, cov cuab yeej ntawm cov cuab yeej ntawm tes raug kev txom nyem. Cov fatty acids uas ua rau bilipid txheej ntawm cell membranes kuj oxidized. Qhov no cuam tshuam rau lawv cov permeability, kev ua haujlwm ntawm cov twj tso kua mis electrolyte, thiab qhov chaw ntawm cov receptors.
Microsomal oxidation inhibitors yog cov tshuaj antioxidants. Lawv muaj nyob rau hauv cov zaub mov thiab tsim nyob rau hauv lub cev. Qhov zoo tshaj plaws paub antioxidant yog vitamin E. Cov tshuaj no tuaj yeem inhibit microsomal oxidation. Biochemistry piav qhia txog kev sib cuam tshuam ntawm lawv raws li lub ntsiab lus tawm tswv yim. Ntawd yog, oxidases ntau dua, lawv muaj zog dua, thiab rov ua dua. Qhov no yuav pab kom muaj kev sib npaug ntawm cov kab ke thiab qhov chaw nyob ib puag ncig.
Electric transport chain
Lub microsomal oxidation system tsis muaj cov khoom soluble hauv cytoplasm, yog li tag nrho nws cov enzymes tau sau rau ntawm qhov chaw ntawm endoplasmic reticulum. Cov kab ke no suav nrog ntau cov proteins uas tsim cov saw hlau electrotransport:
- NADP-P450 reductase thiab cytochrome P450;
- OVER-cytochrome B5 reductase thiab cytochrome B5;
- steatoryl-CoA desaturase.
Tus neeg pub khoom siv hluav taws xob hauv feem ntau yog NADP (nicotinamide adenine dinucleotide phosphate). Nws yog oxidized los ntawm NADP-P450 reductase, uas muaj ob coenzymes (FAD thiab FMN), kom txais electrons. Thaum kawg ntawm cov saw hlau, FMN yog oxidized nrog P450.
YCytochrome P450
Qhov no yog microsomal oxidation enzyme, ib qho protein uas muaj heme. Binds oxygen thiab substrate (raws li txoj cai, nws yog xenobiotic). Nws lub npe yog txuam nrog kev nqus ntawm lub teeb los ntawm lub wavelength ntawm 450 nm. Biologists pom nws nyob rau hauv tag nrho cov muaj sia nyob. Tam sim no, ntau tshaj kaum ib txhiab proteins uas yog ib feem ntawm cytochrome P450 system tau piav qhia. Nyob rau hauv cov kab mob, cov tshuaj no yog yaj nyob rau hauv lub cytoplasm, thiab nws yog ntseeg hais tias daim ntawv no yog lub feem ntau evolutionarily ancient tshaj nyob rau hauv tib neeg. Nyob rau hauv peb lub teb chaws, cytochrome P450 yog ib tug parietal protein tsau nyob rau hauv endoplasmic membrane.
Enzymes ntawm pab pawg no koom nrog cov metabolism hauv steroids, kua tsib thiab fatty acids, phenols, neutralization ntawm cov tshuaj, tshuaj lom lossis tshuaj.
Txoj kev ntawm microsomal oxidation
txheej txheem ntawm microsomaloxidation muaj ib tug dav substrate specification, thiab qhov no, nyob rau hauv lem, ua rau nws muaj peev xwm mus neutralize ntau yam khoom. Kaum ib txhiab cytochrome P450 cov proteins tuaj yeem muab tais rau hauv ntau tshaj li ib puas thiab tsib caug isoforms ntawm cov enzyme no. Txhua ntawm lawv muaj ntau tus substrates. Qhov no ua rau lub cev tshem tawm yuav luag txhua yam teeb meem uas tau tsim hauv nws lossis los ntawm sab nraud. Ua nyob rau hauv daim siab, microsomal oxidation enzymes tuaj yeem ua ob qho tib si hauv zos thiab ntawm qhov deb ntawm lub cev.
Txoj cai ntawm microsomal oxidation kev ua haujlwm
Microsomal oxidation nyob rau hauv lub siab yog tswj nyob rau hauv lub theem ntawm messenger RNA, los yog theej nws muaj nuj nqi - transcription. Txhua qhov sib txawv ntawm cytochrome P450, piv txwv li, raug kaw rau ntawm DNA molecule, thiab kom nws tshwm sim ntawm EPR, nws yog ib qho tsim nyog yuav tau "rewrite" ib feem ntawm cov ntaub ntawv los ntawm DNA mus rau tus tub txib RNA. Lub mRNA ces xa mus rau ribosomes, qhov twg protein molecules tsim. Tus naj npawb ntawm cov molecules no yog tswj los ntawm sab nraud thiab nyob ntawm tus nqi ntawm cov tshuaj uas yuav tsum tau deactivated, nrog rau qhov muaj cov amino acids tsim nyog.
Txog hnub tim, ntau tshaj li ob puas thiab tsib caug cov tshuaj lom neeg tau piav qhia tias ua kom microsomal oxidation hauv lub cev. Cov no suav nrog barbiturates, aromatic carbohydrates, cawv, ketones, thiab cov tshuaj hormones. Txawm hais tias muaj ntau haiv neeg, tag nrho cov tshuaj no yog lipophilic (fat-soluble), thiab yog li cuam tshuam rau cytochrome P450.
