Hauv tsab xov xwm no peb yuav sim piav qhia hauv txoj hauv kev nkag mus tau li cas pyruvate dehydrogenase complex yog thiab biochemistry ntawm cov txheej txheem, qhia txog cov enzymes thiab coenzymes, qhia lub luag haujlwm thiab qhov tseem ceeb ntawm cov txheej txheem no. thiab tib neeg lub neej. Tsis tas li ntawd, qhov tshwm sim ntawm kev ua txhaum ntawm kev ua haujlwm ntawm lub hom phiaj ntawm qhov nyuaj thiab lub sijhawm ntawm lawv qhov tshwm sim yuav raug txiav txim siab.
Introduction to the concept
Pyruvate dehydrogenase complex (PDH) yog ib hom protein ntau complex uas nws lub luag haujlwm yog ua kom oxidation ntawm pyruvate los ntawm decarboxylation. Cov complex no muaj 3 enzymes, nrog rau ob qho proteins uas tsim nyog rau kev siv cov haujlwm pabcuam. Rau cov pyruvate dehydrogenase complex ua haujlwm, qee cov cofactors yuav tsum muaj. Muaj tsib ntawm lawv: CoA, nicotinamide adenine dinucleotide, flavin adenine dinucleotide, thiamine pyrophosphate thiab lipoate.
Localization ntawm PDH hauv cov kab mob kab mob yog concentrated hauv cytoplasm, eukaryotic hlwb khaws ciahauv matrix ntawm mitochondria.
Koom nrog pyruvate decarboxylation
Qhov tseem ceeb ntawm pyruvate dehydrogenase complex yog nyob rau hauv cov tshuaj tiv thaiv oxidation ntawm pyruvate. Xav txog qhov tseem ceeb ntawm txoj kev no.
Lub tshuab ntawm pyruvate oxidation nyob rau hauv kev cuam tshuam ntawm decarboxylation yog txheej txheem ntawm biochemical xwm, nyob rau hauv uas lub cleavage ntawm CO 2 molecule nyob rau hauv cov lus tshwm sim, thiab ces qhov no. molecule yog ntxiv rau pyruvate, raug rau decarboxylation thiab teej tug mus rau coenzyme A (CoA). Qhov no yog li cas acetyl-KoA tsim. Qhov tshwm sim no nyob hauv ib qho chaw nruab nrab ntawm cov txheej txheem ntawm glycolysis thiab tricarboxylic acid voj voog. Cov txheej txheem ntawm pyruvate dicarboxylation yog ua tiav nrog kev koom tes ntawm MPC complex, uas, raws li tau hais dhau los, suav nrog peb enzymes thiab ob lub koom haum pabcuam proteins.
Lub luag haujlwm ntawm coenzymes
Rau cov pyruvate dehydrogenase complex, enzymes ua lub luag haujlwm tseem ceeb. Txawm li cas los xij, lawv tuaj yeem pib lawv txoj haujlwm tsuas yog nyob rau hauv lub xub ntiag ntawm tsib coenzymes los yog pab pawg ntawm cov prosthetic hom uas tau teev saum toj no. Cov txheej txheem nws tus kheej thaum kawg yuav ua rau qhov tseeb tias pawg acyl yuav suav nrog hauv CoA-acetyl. Hais txog coenzymes, koj yuav tsum paub tias plaub ntawm lawv muaj cov vitamin derivatives: thiamine, riboflavin, niacin thiab pantothenic acid.
Flavina adenine dinucleotide thiab nicotinamide adenine dinucleotide koom nrog hauv kev hloov hluav taws xob, thiab thiamine pyrophosphate, paub rau ntau yam.pyruvate decarboxylic coenzyme, nkag mus rau hauv cov tshuaj fermentation.
Kev ua ntawm pawg thiol
Acetylation coenzyme (A) - muaj cov pab pawg thiol-hom (-SH), uas yog cov nquag ua haujlwm, nws yog ib qho tseem ceeb thiab tsim nyog rau CoA ua haujlwm raws li cov khoom uas tuaj yeem hloov cov acyl pawg rau thiol thiab daim ntawv. thioether. Esters ntawm thiols (thioethers) muaj tus nqi siab ntawm hydrolysis lub zog ntawm cov xwm txheej dawb, yog li lawv muaj peev xwm hloov tau cov pab pawg acyl mus rau ntau yam ntawm cov neeg txais cov molecules. Yog vim li cas acetyl CoA thiaj li hu ua activated CH3COOH.
Electron transfer
Ntxiv rau plaub lub cofactors uas yog cov txiaj ntsig ntawm cov vitamins, muaj 5th cofactor ntawm pyruvate dehydrogenase complex, hu ua lipoate. Nws muaj 2 pawg thiol-hom uas tuaj yeem thim rov qab oxidation, uas ua rau tsim cov nyiaj disulfide (-S-S-), uas zoo ib yam li cov txheej txheem no ua haujlwm ntawm cov amino acids thiab cysteine residues hauv cov protein. Lub peev xwm los oxidize thiab rov qab muab cov lipoate lub peev xwm los ua tus cab kuj tsis yog ntawm acyl pawg, tab sis kuj ntawm electrons.
Cov khoom siv Enzymatic
Ntawm cov enzymes, pyruvate dehydrogenase complex suav nrog peb lub ntsiab. Thawj enzyme yog pyruvate dehydrosenase (E1). Qhov thib ob enzyme yogdihydrolipoyl dehydrogenase (E3). Qhov thib peb yog dihydrolipoyltransacetylase (E2). Lub pyruvate dehydrogenase complex suav nrog cov enzymes, khaws cia rau hauv ntau daim ntawv luam. Tus naj npawb ntawm cov ntawv luam ntawm txhua tus enzyme tuaj yeem sib txawv, thiab yog li qhov loj ntawm txoj kev tuaj yeem sib txawv heev. Lub PDH complex nyob rau hauv cov tsiaj yog hais txog 50 nanometers nyob rau hauv lub cheeb. Qhov no yog 5-6 lub sij hawm loj dua li txoj kab uas hla ntawm ribosome. Cov complexes no loj heev, yog li lawv tuaj yeem ua qhov txawv ntawm lub tshuab ntsuas hluav taws xob.
Cov kab mob gram-zoo bacillus stearothermophilus muaj rau caum daim ntawv luam zoo ib yam ntawm dihydrolipoyl transacetylase hauv nws PDH, uas dhau los ua ib qho pentagonal-hom dodecahedron kwv yees li 25 nanometers inch. Cov kab mob gram-zoo Escherichia coli muaj nees nkaum plaub daim ntawv E2, miv. txuas cov pab pawg neeg prosthetic ntawm lipoate rau nws tus kheej, thiab nws tsim ib qho amide-type bond nrog cov amino pawg ntawm cov lysine residue suav nrog E2.
Dihydrolipoyltransacetylase yog tsim los ntawm kev sib cuam tshuam ntawm 3 lub npe uas muaj qhov sib txawv ua haujlwm. Cov no yog: aminoterminal lipoyl domain uas muaj lysine residue thiab txuam nrog lipoate; binding domain (central E1- thiab E3-); Internal acyltransferase domain, uas muaj xws li active hom acyltransferase chaw zov me nyuam.
Cov poov xab pyruvate dehydrogenase complex muaj tsuas yog ib hom lipoyl-hom npe, cov tsiaj muaj ob hom, thiab cov kab mob Escherichia coli muaj peb. Qhov sib txuas ntawm cov amino acids uas yogntawm nees nkaum mus rau peb caug amino acid residues, sib koom E2, thaum alanine thiab proline residues interspersed nrog amino acid residues uas raug them. Cov linkers no feem ntau muaj cov duab txuas ntxiv. Cov yam ntxwv no cuam tshuam qhov tseeb tias lawv sib koom 3 lub npe.
Kev sib raug zoo ntawm Keeb Kwm
E1 tsim kev sib txuas nrog TTP nrog nws qhov chaw nquag, thiab lub chaw nquag E3 tsim kev sib txuas nrog FAD. Tib neeg lub cev muaj cov enzyme E1 nyob rau hauv daim ntawv ntawm tetramer, uas muaj plaub subunits: ob E1alpha thiab ob E 1beta. Kev tswj hwm cov protein tau nthuav tawm hauv daim ntawv ntawm cov protein kinase thiab phosphoprotein phosphatase. Hom qauv no (E1- E2- E 3) tseem yog ib feem ntawm kev saib xyuas hauv kev qhia evolutionary. Cov complexes nrog cov qauv thiab cov qauv zoo sib xws tuaj yeem koom nrog ntau yam kev cuam tshuam uas txawv ntawm cov qauv, piv txwv li, thaum α-ketoglutarate yog oxidized thaum lub voj voog Krebs, α-keto acid kuj yog oxidized, uas tau tsim los ntawm kev siv catabolic. Ntawm ceg-hom amino acids: valine, leucine thiab isoleucine.
YPyruvate dehydrogenase complex muaj cov enzyme E
3, uas tseem pom muaj nyob hauv lwm qhov chaw. Qhov zoo sib xws ntawm cov qauv protein, cofactors thiab cov tshuaj tiv thaiv mechanisms taw qhia rau cov hauv paus chiv keeb. Cov lipoate txuas nrog rau lysine E 2, thiab ib hom "tes" yog tsim uas tuaj yeem txav los ntawm qhov chaw nquag E1 mus rau active chaw E 2 thiabE3, uas yog kwv yees li 5 nm.
Eukaryotes hauv pyruvate dehydrogenase complex muaj kaum ob subunits ntawm E3BP (E3 - cov protein uas tsis yog catalytic). Qhov chaw tseeb ntawm cov protein no tsis paub. Muaj ib qho kev xav tias cov protein no hloov qee qhov ntawm cov subed. E2 hauv nyuj PDH.
Kev sib txuas lus nrog cov kab mob
Qhov kev txiav txim siab yog qhov muaj nyob hauv qee hom kab mob anaerobic. Txawm li cas los xij, tus naj npawb ntawm cov kab mob uas muaj PDH hauv lawv cov qauv yog me me. Cov dej num ua los ntawm cov kab mob complex, raws li txoj cai, raug txo rau cov txheej txheem dav dav. Piv txwv li, lub luag hauj lwm ntawm pyruvate dehydrogenase complex nyob rau hauv cov kab mob Zymonomonas mobilis yog cawv fermentation. Pyruvate cov kab mob ntau txog 98% yuav raug siv rau cov laj thawj zoo li no. Qhov seem ob peb feem pua yog oxidized rau carbon dioxide, nicotinamide adenine dinucleotide, acetyl-CoA, thiab lwm yam. Cov qauv ntawm pyruvate dehydrogenase complex nyob rau hauv Zymomonas mobilis yog nthuav. Cov kab mob no muaj plaub enzymes: E1alpha, E1beta, E2 thiab E 3. PDH ntawm cov kab mob no muaj lipoyl domain nyob rau hauv E1beta, uas ua rau nws txawv. Lub hauv paus ntawm lub complex yog E2, thiab lub koom haum ntawm lub complex nws tus kheej siv lub pentagonal dodecahedron. Zymomonas mobilis tsis muaj tag nrho cov enzymes ntawm lub voj voog tricarboxylic acid, thiab yog li ntawd nws cov PDH tsuas yog koom nrog cov haujlwm anabolic.
PDH hauv txiv neej
Txiv neej, zoo li lwm yam kab mob nyob,muaj gene encoding PDH. Cov noob E1alpha – PDHA 1 yog nyob rau ntawm X chromosome. rau PDH deficiency. Cov tsos mob ntawm tus kab mob tuaj yeem sib txawv heev los ntawm cov teeb meem me me ntawm lactic acidosis mus rau qhov ua rau tuag malformations hauv kev loj hlob ntawm lub cev. Cov txiv neej uas nws X chromosome suav nrog ib qho allele zoo li yuav tuag sai sai thaum tseem hluas. Cov poj niam kuj raug cuam tshuam los ntawm tus kab mob no, tab sis tsawg dua, thiab qhov teeb meem nws tus kheej yog inactivation ntawm X chromosome.
Teeb meem ntawm kev hloov pauv
E1beta - PDHB - nyob ntawm peb chromosome. Tsuas yog ob qho alleles ntawm hom mutant paub txog cov noob no, uas, nyob rau hauv txoj haujlwm homozygous, ua rau muaj qhov tshwm sim tuag thoob plaws hauv lub xyoo, uas cuam tshuam nrog malformations.
Tej zaum muaj lwm cov alleles zoo sib xws uas tuaj yeem ua rau tuag ua ntej kev loj hlob tag nrho ntawm lub cev. E2 - DLAT - concentrated ntawm kaum ib chromosome. Tib neeg paub txog ob qho alleles ntawm cov noob no uas yuav tsim teeb meem yav tom ntej, tab sis kev noj zaub mov zoo tuaj yeem them rov qab rau qhov no. Muaj lub caij nyoog siab uas tus menyuam hauv plab yuav tuag hauv plab vim muaj lwm yam kev hloov pauv hauv cov noob no. E3 - dld - nyob rau ntawm xya chromosome thiab suav nrog ntau tus alleles. TxausIb feem loj ntawm lawv ua rau muaj qhov tshwm sim ntawm cov kab mob ntawm caj ces, uas yuav cuam tshuam nrog kev ua txhaum ntawm cov amino acid metabolism.
Zoo kawg
Peb tau txiav txim siab tias qhov tseem ceeb ntawm pyruvate dehydrogenase complex yog rau cov kab mob nyob. Cov kev tshwm sim tshwm sim hauv nws yog feem ntau tsom rau ntawm decarboxylation ntawm pyruvate los ntawm oxidation, thiab PDH nws tus kheej yog qhov tshwj xeeb, tab sis nyob rau hauv cov xwm txheej sib txawv, nrog rau qee yam laj thawj, nws tuaj yeem ua haujlwm ntawm qhov sib txawv, piv txwv li, koom nrog fermentation. Peb kuj pom tias cov protein-hom complexes uas koom nrog hauv pyruvate oxidation muaj tsib enzymes uas tseem ua haujlwm tsuas yog muaj tsib cofactors. Txhua qhov kev hloov pauv hauv lub algorithm ntawm cov txheej txheem nyuaj ntawm decarboxylation tuaj yeem ua rau mob hnyav thiab ua rau tus neeg tuag.
