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Waarom word NAD+ verminder as dit 'n waterstofproton kry?

Waarom word NAD+ verminder as dit 'n waterstofproton kry?


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Ek het gehoor $ce{NAD^+}$ kry 'n waterstofproton tydens glikolise en die Krebs-siklus en word verminder na $ce{NADH}$. Is reduksie egter nie wanneer 'n molekule 'n elektron ontvang nie?

Is ek dalk verkeerd ingelig? Kry $ce{NADH}$ 'n waterstofelektron, nie 'n proton nie?


Jy is korrek dat reduksie bloot 'n wins van elektrone is. Dit lei tot 'n afname in oksidasiegetal.

Jy weet daardie NAD+ word deur hierdie proses verminder omdat dit met 'n positiewe lading (+1) begin en met 'n neutrale lading (0) eindig.

Die reduseermiddel wat die elektrone skenk, is die waterstof. Meer korrek, die elektrone kom van die hidried (H-).

Die hidried word deur 2 elektrone op hierdie redoksdiagram voorgestel:

Soos u kan sien, dra die reduksiereaksie 'n proton oor (H+) en hidriedelektrone (H- of 2e-) na NAD+. Een elektron gaan na die stikstof, en die ander na die koolstof waar die proton bind. Meer besonderhede oor die redoksreaksie van NAD kan hier gevind word.


Waarom word die verkryging van waterstof reduksie genoem terwyl die verkryging van elektrone reduksie genoem word? Is hulle nie teenoorgesteldes nie

Is dit omdat 'n waterstof 'n elektron het, sodat die verkryging van waterstof tegnies elektrone bykry? Maar dit lyk nie reg nie aangesien suurstof ook elektrone het en om suurstof by te kry is oksidasie.

Wat my verwar, is wanneer ons gewoonlik oor waterstof praat, dit is 'n waterstofioon. En waterstofione en elektrone is teenoorgesteld. Ek besef hierdie situasie is nie 'n waterstofioon nie, maar 'n volle waterstof, maar dit doen steeds my kop.


Inhoud

Nikotinamied adenien dinukleotied bestaan ​​uit twee nukleosiede wat deur pirofosfaat verbind is. Die nukleosiede bevat elk 'n ribosering, een met adenien geheg aan die eerste koolstofatoom (die 1'-posisie) (adenosiendifosfaatribose) en die ander met nikotinamied op hierdie posisie. [1] [2]

Die verbinding aanvaar of skenk die ekwivalent van H − . [3] Sulke reaksies (in formule hieronder opgesom) behels die verwydering van twee waterstofatome uit die reaktant (R), in die vorm van 'n hidriedioon (H − ), en 'n proton (H + ). Die proton word in oplossing vrygestel, terwyl die reduktant RH2 word geoksideer en NAD + gereduseer na NADH deur oordrag van die hidried na die nikotinamiedring.

Van die hidried-elektronpaar word een elektron oorgedra na die positief gelaaide stikstof van die nikotinamiedring van NAD +, en die tweede waterstofatoom oorgedra na die C4 koolstofatoom oorkant hierdie stikstof. Die middelpuntpotensiaal van die NAD + /NADH redokspaar is -0.32 volt, wat NADH 'n sterk maak verminder agent. [4] Die reaksie is maklik omkeerbaar, wanneer NADH 'n ander molekule verminder en weer na NAD + geoksideer word. Dit beteken die koënsiem kan voortdurend tussen die NAD + en NADH vorms siklus sonder om verteer te word. [2]

In voorkoms is alle vorme van hierdie koënsiem wit amorfe poeiers wat higroskopies en hoogs wateroplosbaar is. [5] Die vaste stowwe is stabiel as dit droog en in die donker gestoor word. Oplossings van NAD + is kleurloos en stabiel vir ongeveer 'n week by 4 °C en neutrale pH, maar ontbind vinnig in sure of alkalieë. By ontbinding vorm hulle produkte wat ensieminhibeerders is. [6]

Beide NAD + en NADH absorbeer ultravioletlig sterk as gevolg van die adenien. Byvoorbeeld, piekabsorpsie van NAD + is by 'n golflengte van 259 nanometer (nm), met 'n uitsterwingskoëffisiënt van 16 900 M −1 cm −1. NADH absorbeer ook by hoër golflengtes, met 'n tweede piek in UV-absorpsie by 339 nm met 'n uitsterwingskoëffisiënt van 6,220 M −1 cm −1. [7] Hierdie verskil in die ultraviolet absorpsiespektra tussen die geoksideerde en gereduseerde vorme van die koënsieme by hoër golflengtes maak dit maklik om die omskakeling van een na 'n ander in ensiemtoetse te meet – deur die hoeveelheid UV-absorpsie by 340 nm met behulp van 'n spektrofotometer te meet . [7]

NAD + en NADH verskil ook in hul fluoressensie. Vrylik diffusie van NADH in waterige oplossing, wanneer opgewonde oor die nikotinamied absorpsie van

335 nm (naby UV), fluoresseer by 445-460 nm (violet tot blou) met 'n fluoressensie-leeftyd van 0.4 nanosekondes, terwyl NAD + nie fluoresseer nie. [8] [9] Die eienskappe van die fluoressensiesein verander wanneer NADH aan proteïene bind, dus kan hierdie veranderinge gebruik word om dissosiasiekonstantes te meet, wat nuttig is in die studie van ensiemkinetika. [9] [10] Hierdie veranderinge in fluoressensie word ook gebruik om veranderinge in die redokstoestand van lewende selle te meet, deur middel van fluoressensiemikroskopie. [11]

In rotlewer is die totale hoeveelheid NAD + en NADH ongeveer 1 μmol per gram nat gewig, ongeveer 10 keer die konsentrasie van NADP + en NADPH in dieselfde selle. [12] Die werklike konsentrasie van NAD + in sel-sitosol is moeiliker om te meet, met onlangse skattings in dierselle wat wissel van ongeveer 0.3 mM, [13] [14] en ongeveer 1.0 tot 2.0 mM in gis. [15] Meer as 80% van NADH-fluoressensie in mitochondria is egter van gebonde vorm, dus is die konsentrasie in oplossing baie laer. [16]

NAD + konsentrasies is die hoogste in die mitochondria, wat 40% tot 70% van die totale sellulêre NAD + uitmaak. [17] NAD + in die sitosol word deur 'n spesifieke membraantransportproteïen in die mitochondrion gedra, aangesien die koënsiem nie oor membrane kan diffundeer nie. [18] Die intrasellulêre halfleeftyd van NAD + is volgens een hersiening tussen 1-2 uur beweer, [19] terwyl 'n ander oorsig verskillende skattings gegee het gebaseer op kompartement: intrasellulêre 1-4 uur, sitoplasmiese 2 uur en mitochondriale 4 – 6 uur. [20]

Die balans tussen die geoksideerde en gereduseerde vorms van nikotinamied adenien dinukleotied word die NAD + /NADH verhouding genoem. Hierdie verhouding is 'n belangrike komponent van wat genoem word die redoks toestand van 'n sel, 'n meting wat beide die metaboliese aktiwiteite en die gesondheid van selle weerspieël. [21] Die effekte van die NAD + /NADH-verhouding is kompleks, wat die aktiwiteit van verskeie sleutelensieme beheer, insluitend gliseraldehied-3-fosfaatdehidrogenase en piruvaatdehidrogenase. In gesonde soogdierweefsels lê skattings van die verhouding tussen vry NAD + en NADH in die sitoplasma tipies rondom 700:1 die verhouding is dus gunstig vir oksidatiewe reaksies. [22] [23] Die verhouding van totale NAD + /NADH is baie laer, met skattings wat wissel van 3–10 in soogdiere. [24] Daarteenoor is die NADP + /NADPH-verhouding normaalweg ongeveer 0,005, dus is NADPH die dominante vorm van hierdie koënsiem. [25] Hierdie verskillende verhoudings is die sleutel tot die verskillende metaboliese rolle van NADH en NADPH.

NAD + word deur twee metaboliese weë gesintetiseer. Dit word óf in 'n De novo pad vanaf aminosure of in bergingsweë deur voorafgevormde komponente soos nikotinamied terug te herwin na NAD+. Alhoewel die meeste weefsels NAD + sintetiseer deur die reddingsweg in soogdiere, veel meer De novo sintese vind plaas in die lewer vanaf triptofaan, en in die niere en makrofage van nikotiensuur. [26]

De novo produksie Edit

Die meeste organismes sintetiseer NAD + uit eenvoudige komponente. [3] Die spesifieke stel reaksies verskil tussen organismes, maar 'n algemene kenmerk is die generering van kinoliensuur (QA) vanaf 'n aminosuur - óf triptofaan (Trp) in diere en sommige bakterieë, óf asparaginsuur (Asp) in sommige bakterieë en plante. [27] [28] Die kinoliensuur word omgeskakel na nikotiensuurmononukleotied (NaMN) deur oordrag van 'n fosforibose-deel. 'n Adenilaatdeel word dan oorgedra om nikotiensuur adenien dinukleotied (NaAD) te vorm. Laastens word die nikotiensuurdeel in NaAD geamideer na 'n nikotinamied (Nam) deel, wat nikotinamied adenien dinukleotied vorm. [3]

In 'n verdere stap word sommige NAD + omgeskakel na NADP + deur NAD + kinase, wat NAD + fosforileer. [29] In die meeste organismes gebruik hierdie ensiem ATP as die bron van die fosfaatgroep, hoewel verskeie bakterieë soos bv. Mycobacterium tuberculosis en 'n hipertermofiele argeon Pyrococcus horikoshii, gebruik anorganiese polifosfaat as 'n alternatiewe fosforielskenker. [30] [31]

Bergingspaaie Wysig

Ten spyte van die teenwoordigheid van die De novo pad, die reddingsreaksies is noodsaaklik by mense 'n gebrek aan niasien in die dieet veroorsaak die vitamien-tekort siekte pellagra. [32] Hierdie hoë vereiste vir NAD + is die gevolg van die konstante verbruik van die koënsiem in reaksies soos posttranslasionele modifikasies, aangesien die siklus van NAD + tussen geoksideerde en gereduseerde vorms in redoksreaksies nie die algehele vlakke van die koënsiem verander nie. [3] Die hoofbron van NAD + in soogdiere is die reddingsweg wat die nikotinamied herwin wat deur ensieme geproduseer word wat NAD + gebruik. [33] Die eerste stap, en die tempo-beperkende ensiem in die reddingsweg is nikotinamiedfosforibosieltransferase (NAMPT), wat nikotinamiedmononukleotied (NMN) produseer. [33] NMN is die onmiddellike voorloper van NAD+ in die bergingspad. [34]

Behalwe die samestelling van NAD + De novo van eenvoudige aminosuurvoorlopers red selle ook voorafgevormde verbindings wat 'n piridienbasis bevat. Die drie vitamienvoorlopers wat in hierdie reddingsmetaboliese weë gebruik word, is nikotiensuur (NA), nikotinamied (Nam) en nikotinamiedribosied (NR). [3] Hierdie verbindings kan uit die dieet opgeneem word en word vitamien B genoem3 of niasien. Hierdie verbindings word egter ook binne selle en deur vertering van sellulêre NAD + geproduseer. Sommige van die ensieme betrokke by hierdie reddingsweë blyk in die selkern gekonsentreer te wees, wat kan kompenseer vir die hoë vlak van reaksies wat NAD + in hierdie organel verbruik. [35] Daar is 'n paar verslae dat soogdierselle ekstrasellulêre NAD + uit hul omgewing kan opneem, [36] en beide nikotinamied en nikotinamied ribosied kan uit die ingewande geabsorbeer word. [37]

Die bergingsweë wat in mikroörganismes gebruik word, verskil van dié van soogdiere. [38] Sommige patogene, soos die gis Candida glabrata en die bakterie Haemophilus influenzae is NAD + eksotrofe – hulle kan nie NAD + sintetiseer nie – maar beskik oor reddingsweë en is dus afhanklik van eksterne bronne van NAD + of sy voorlopers. [39] [40] Selfs meer verbasend is die intrasellulêre patogeen Chlamydia trachomatis, wat nie herkenbare kandidate het vir enige gene wat betrokke is by die biosintese of herwinning van beide NAD + en NADP + nie, en moet hierdie koënsieme van sy gasheer verkry. [41]

Nikotinamied adenien dinukleotied het verskeie noodsaaklike rolle in metabolisme. Dit tree op as 'n koënsiem in redoksreaksies, as 'n skenker van ADP-ribose-eenhede in ADP-ribosileringsreaksies, as 'n voorloper van die tweede boodskappermolekule sikliese ADP-ribose, sowel as dien as 'n substraat vir bakteriese DNA-ligases en 'n groep van ensieme genaamd sirtuine wat NAD + gebruik om asetielgroepe uit proteïene te verwyder. Benewens hierdie metaboliese funksies, kom NAD + na vore as 'n adeniennukleotied wat spontaan en deur gereguleerde meganismes uit selle vrygestel kan word, [43] [44] en kan dus belangrike ekstrasellulêre rolle hê. [44]

Oksidoreduktase binding van NAD Edit

Die hoofrol van NAD + in metabolisme is die oordrag van elektrone van een molekule na 'n ander. Reaksies van hierdie tipe word gekataliseer deur 'n groot groep ensieme wat oksidoreduktases genoem word. Die korrekte name vir hierdie ensieme bevat die name van albei hul substrate: byvoorbeeld NADH-ubiquinone oksidoreduktase kataliseer die oksidasie van NADH deur koënsiem Q. [45] Daar word egter ook na hierdie ensieme verwys as dehidrogenases of reduktase, met NADH-ubiquinoon-oksidoreduktase wat algemeen genoem word NADH dehidrogenase of soms koënsiem Q reduktase. [46]

Daar is baie verskillende superfamilies van ensieme wat NAD + / NADH bind. Een van die mees algemene superfamilies sluit in 'n strukturele motief bekend as die Rossmann-vou. [47] [48] Die motief is vernoem na Michael Rossmann wat die eerste wetenskaplike was wat opgemerk het hoe algemeen hierdie struktuur binne nukleotiedbindende proteïene voorkom. [49]

'n Voorbeeld van 'n NAD-bindende bakteriese ensiem betrokke by aminosuurmetabolisme wat nie Rossmann-vou het nie, word gevind in Pseudomonas syringae pv. tamatie ( PDB: 2CWH ​ InterPro: IPR003767). [50]

Wanneer gebind in die aktiewe plek van 'n oksidoreduktase, word die nikotinamiedring van die koënsiem so geposisioneer dat dit 'n hidried van die ander substraat kan aanvaar. Afhangende van die ensiem, is die hidriedskenker óf "bo" óf "onder" die vlak van die vlakke C4 koolstof geposisioneer, soos in die figuur gedefinieer. Klas A-oksidoreduktase dra die atoom van bo af oor klas B-ensieme dra dit van onder af. Aangesien die C4-koolstof wat die waterstof aanvaar prochiraal is, kan dit in ensiemkinetika ontgin word om inligting oor die ensiem se meganisme te gee. Dit word gedoen deur 'n ensiem te meng met 'n substraat wat deuteriumatome het wat die waterstowwe vervang, dus sal die ensiem NAD + verminder deur deuterium eerder as waterstof oor te dra. In hierdie geval kan 'n ensiem een ​​van twee stereoisomere van NADH produseer. [51]

Ten spyte van die ooreenkoms in hoe proteïene die twee koënsieme bind, toon ensieme byna altyd 'n hoë vlak van spesifisiteit vir óf NAD + óf NADP +. [52] Hierdie spesifisiteit weerspieël die afsonderlike metaboliese rolle van die onderskeie koënsieme, en is die resultaat van duidelike stelle aminosuurreste in die twee tipes koënsiem-bindende sak. Byvoorbeeld, in die aktiewe plek van NADP-afhanklike ensieme, word 'n ioniese binding tussen 'n basiese aminosuur-syketting en die suur fosfaatgroep van NADP + gevorm. Omgekeerd, in NAD-afhanklike ensieme is die lading in hierdie sak omgekeer, wat verhoed dat NADP + bind. Daar is egter 'n paar uitsonderings op hierdie algemene reël, en ensieme soos aldose-reduktase, glukose-6-fosfaatdehidrogenase en metileentetrahidrofolaatreduktase kan beide koënsieme in sommige spesies gebruik. [53]

Rol in redoksmetabolisme Edit

Die redoksreaksies wat deur oksidoreduktase gekataliseer word, is noodsaaklik in alle dele van metabolisme, maar een besonder belangrike funksie van hierdie reaksies is om voedingstowwe in staat te stel om die energie wat in die relatief swak dubbelbinding van suurstof gestoor word, te ontsluit. [54] Hier word gereduseerde verbindings soos glukose en vetsure geoksideer, waardeur die chemiese energie van O vrygestel word.2. In hierdie proses word NAD + tot NADH gereduseer, as deel van beta-oksidasie, glikolise en die sitroensuursiklus. In eukariote word die elektrone wat deur die NADH gedra word wat in die sitoplasma geproduseer word na die mitochondrion oorgedra (om mitochondriale NAD + te verminder) deur mitochondriale pendeltuie, soos die malaat-aspartaat-pendeltuig. [55] Die mitochondriale NADH word dan op sy beurt geoksideer deur die elektronvervoerketting, wat protone oor 'n membraan pomp en ATP genereer deur oksidatiewe fosforilering. [56] Hierdie pendelstelsels het ook dieselfde vervoerfunksie in chloroplaste. [57]

Aangesien beide die geoksideerde en gereduseerde vorme van nikotinamied adenien dinukleotied in hierdie gekoppelde stelle reaksies gebruik word, handhaaf die sel beduidende konsentrasies van beide NAD + en NADH, met die hoë NAD + /NADH verhouding wat hierdie koënsiem toelaat om as beide 'n oksiderende en 'n reduseermiddel. [58] Daarteenoor is die hooffunksie van NADPH as 'n reduseermiddel in anabolisme, met hierdie koënsiem wat betrokke is by weë soos vetsuursintese en fotosintese. Aangesien NADPH nodig is om redoksreaksies as 'n sterk reduseermiddel te dryf, word die NADP + /NADPH verhouding baie laag gehou. [58]

Alhoewel dit belangrik is in katabolisme, word NADH ook gebruik in anaboliese reaksies, soos glukoneogenese. [59] Hierdie behoefte aan NADH in anabolisme stel 'n probleem vir prokariote wat groei op voedingstowwe wat slegs 'n klein hoeveelheid energie vrystel. Byvoorbeeld, nitrifiserende bakterieë soos Nitrobakter oksideer nitriet na nitraat, wat voldoende energie vrystel om protone te pomp en ATP te genereer, maar nie genoeg om NADH direk te produseer nie. [60] Aangesien NADH steeds nodig is vir anaboliese reaksies, gebruik hierdie bakterieë 'n nitrietoksidoreduktase om genoeg proton-motorkrag te produseer om 'n deel van die elektronvervoerketting omgekeerd te laat loop, wat NADH genereer. [61]

Nie-redoksrolle Wysig

Die koënsiem NAD + word ook verbruik in ADP-ribose-oordragreaksies. Byvoorbeeld, ensieme genaamd ADP-ribosieltransferases voeg die ADP-ribose-deel van hierdie molekule by proteïene, in 'n posttranslasionele modifikasie genaamd ADP-ribosilering. [62] ADP-ribosilering behels óf die byvoeging van 'n enkele ADP-ribose-deel, in mono-ADP-ribosilering, of die oordrag van ADP-ribose na proteïene in lang vertakte kettings, wat genoem word poli(ADP-ribosiel)asie. [63] Mono-ADP-ribosilering is eers geïdentifiseer as die meganisme van 'n groep bakteriese toksiene, veral cholera-toksien, maar dit is ook betrokke by normale selsein. [64] [65] Poli(ADP-ribosiel)asie word deur die poli(ADP-ribose) polimerases uitgevoer. [63] [66] Die poli(ADP-ribose)-struktuur is betrokke by die regulering van verskeie sellulêre gebeurtenisse en is die belangrikste in die selkern, in prosesse soos DNA-herstel en telomere-onderhoud. [66] Benewens hierdie funksies binne die sel, is 'n groep ekstrasellulêre ADP-ribosieltransferases onlangs ontdek, maar hul funksies bly onduidelik. [67] NAD + kan ook by sellulêre RNA gevoeg word as 'n 5'-terminale modifikasie. [68]

Nog 'n funksie van hierdie koënsiem in selsein is as 'n voorloper van sikliese ADP-ribose, wat uit NAD + deur ADP-ribosiel siklases geproduseer word, as deel van 'n tweede boodskapper sisteem. [69] Hierdie molekule tree op in kalsiumsein deur kalsium uit intrasellulêre winkels vry te stel. [70] Dit doen dit deur te bind aan en 'n klas kalsiumkanale oop te maak wat ryanodienreseptore genoem word, wat in die membrane van organelle, soos die endoplasmiese retikulum, geleë is. [71]

NAD + word ook verbruik deur sirtuine, wat NAD-afhanklike deasetylases is, soos Sir2. [72] Hierdie ensieme tree op deur 'n asetielgroep van hul substraatproteïen na die ADP-ribose-deel van NAD oor te dra + dit klief die koënsiem en stel nikotinamied en O-asetiel-ADP-ribose vry. Dit lyk of die sirtuine hoofsaaklik betrokke is by die regulering van transkripsie deur middel van deasetilerende histone en die verandering van nukleosoomstruktuur. [73] Nie-histonproteïene kan egter ook deur sirtuine gedeasetileer word. Hierdie aktiwiteite van sirtuine is veral interessant vanweë hul belangrikheid in die regulering van veroudering. [74]

Ander NAD-afhanklike ensieme sluit bakteriese DNA-ligases in, wat twee DNA-punte verbind deur NAD + as 'n substraat te gebruik om 'n adenosienmonofosfaat (AMP)-eenheid aan die 5'-fosfaat van een DNA-punt te skenk. Hierdie intermediêre word dan aangeval deur die 3'-hidroksielgroep van die ander DNA-kant, wat 'n nuwe fosfodiesterbinding vorm. [75] Dit kontrasteer met eukariotiese DNA-ligases, wat ATP gebruik om die DNA-AMP-tussenproduk te vorm. [76]

Li et al. het gevind dat NAD + proteïen-proteïen interaksies direk reguleer. [77] Hulle toon ook dat een van die oorsake van ouderdomverwante afname in DNA-herstel verhoogde binding van die proteïen DBC1 (Geskrap in Borskanker 1) aan PARP1 (poli[ADP-ribose] polimerase 1) as NAD + vlakke kan wees afname tydens veroudering. [77] Dus kan die modulasie van NAD + beskerm teen kanker, bestraling en veroudering. [77]

Ekstrasellulêre aksies van NAD + Edit

In onlangse jare is NAD + ook erken as 'n ekstrasellulêre seinmolekule betrokke by sel-tot-sel kommunikasie. [44] [78] [79] NAD + word vrygestel uit neurone in bloedvate, [43] urinêre blaas, [43] [80] dikderm, [81] [82] van neurosekretoriese selle, [83] en uit brein sinaptosome, [84] en word voorgestel om 'n nuwe neurotransmitter te wees wat inligting van senuwees na effektorselle in gladdespierorgane oordra. [81] [82] In plante veroorsaak die ekstrasellulêre nikotinamied adenien dinukleotied weerstand teen patogeen infeksie en die eerste ekstrasellulêre NAD reseptor is geïdentifiseer. [85] Verdere studies is nodig om die onderliggende meganismes van sy ekstrasellulêre aksies en die belangrikheid daarvan vir menslike gesondheid en lewensprosesse in ander organismes te bepaal.

Die ensieme wat NAD + en NADH maak en gebruik, is belangrik in beide farmakologie en die navorsing oor toekomstige behandelings vir siektes. [86] Geneesmiddelontwerp en geneesmiddelontwikkeling ontgin NAD + op drie maniere: as 'n direkte teiken van geneesmiddels, deur ensieminhibeerders of -aktiveerders te ontwerp gebaseer op die struktuur daarvan wat die aktiwiteit van NAD-afhanklike ensieme verander, en deur NAD + biosintese te probeer inhibeer. . [87]

Omdat kankerselle verhoogde glikolise gebruik, en omdat NAD glikolise verbeter, word nikotinamied-fosforibosieltransferase (NAD-reddingsweg) dikwels in kankerselle versterk. [88] [89]

Dit is bestudeer vir die potensiële gebruik daarvan in die terapie van neurodegeneratiewe siektes soos Alzheimer se en Parkinson se siekte. [3] 'n Plasebo-beheerde kliniese proef van NADH (wat NADH-voorlopers uitgesluit het) in mense met Parkinson's kon geen effek toon nie. [90]

NAD + is ook 'n direkte teiken van die middel isoniazied, wat gebruik word in die behandeling van tuberkulose, 'n infeksie wat veroorsaak word deur Mycobacterium tuberculosis. Isoniazid is 'n voorgeneesmiddel en sodra dit die bakterieë binnegedring het, word dit geaktiveer deur 'n peroksidase-ensiem, wat die verbinding in 'n vrye radikale vorm oksideer. [91] Hierdie radikaal reageer dan met NADH, om addukte te produseer wat baie kragtige inhibeerders is van die ensieme enoyl-asiel-draerproteïenreduktase, [92] en dihidrofolaatreduktase. [93]

Aangesien 'n groot aantal oksidoreduktase NAD + en NADH as substrate gebruik, en dit bind deur 'n hoogs gekonserveerde strukturele motief, is die idee dat inhibeerders gebaseer op NAD + spesifiek vir een ensiem kan wees, verbasend. [94] Dit kan egter moontlik wees: byvoorbeeld, inhibeerders gebaseer op die verbindings mikofenolsuur en tiazofurin inhibeer IMP dehidrogenase by die NAD + bindingsplek. As gevolg van die belangrikheid van hierdie ensiem in purienmetabolisme, kan hierdie verbindings nuttig wees as anti-kanker, anti-virale of immuunonderdrukkende middels. [94] [95] Ander middels is nie ensieminhibeerders nie, maar aktiveer eerder ensieme betrokke by NAD + metabolisme. Sirtuins is 'n besonder interessante teiken vir sulke middels, aangesien aktivering van hierdie NAD-afhanklike deasetilases lewensduur in sommige dieremodelle verleng. [96] Verbindings soos resveratrol verhoog die aktiwiteit van hierdie ensieme, wat belangrik kan wees in hul vermoë om veroudering in beide gewerwelde, [97] en ongewerwelde model organismes te vertraag. [98] [99] In een eksperiment het muise wat NAD vir een week gegee is, kern-mitochrondriale kommunikasie verbeter. [100]

As gevolg van die verskille in die metaboliese weë van NAD + biosintese tussen organismes, soos tussen bakterieë en mense, is hierdie area van metabolisme 'n belowende area vir die ontwikkeling van nuwe antibiotika. [101] [102] Byvoorbeeld, die ensiem nikotinamidase, wat nikotinamied na nikotiensuur omskakel, is 'n teiken vir geneesmiddelontwerp, aangesien hierdie ensiem afwesig is by mense, maar teenwoordig is in gis en bakterieë. [38]

In bakteriologie word NAD, wat soms na faktor V verwys word, 'n aanvulling tot kultuurmedia vir sommige kieskeurige bakterieë gebruik. [103]

Die koënsiem NAD + is vir die eerste keer deur die Britse biochemici Arthur Harden en William John Young in 1906 ontdek. [104] Hulle het opgemerk dat die byvoeging van gekookte en gefiltreerde gisekstrak alkoholiese fermentasie in ongekookte gisekstrakte aansienlik versnel het. Hulle noem die ongeïdentifiseerde faktor wat vir hierdie effek verantwoordelik is a samesmelting. Deur 'n lang en moeilike suiwering van gisekstrakte is hierdie hitte-stabiele faktor as 'n nukleotiedsuikerfosfaat deur Hans von Euler-Chelpin geïdentifiseer. [105] In 1936 het die Duitse wetenskaplike Otto Heinrich Warburg die funksie van die nukleotiedkoënsiem in hidriedoordrag gewys en die nikotinamiedgedeelte as die plek van redoksreaksies geïdentifiseer. [106]

Vitamienvoorlopers van NAD + is vir die eerste keer in 1938 geïdentifiseer, toe Conrad Elvehjem gewys het dat lewer 'n "anti-swart tong"-aktiwiteit in die vorm van nikotinamied het. [107] Toe, in 1939, het hy die eerste sterk bewys gelewer dat niasien gebruik word om NAD + te sintetiseer. [108] In die vroeë 1940's was Arthur Kornberg die eerste wat 'n ensiem in die biosintetiese pad opgespoor het. [109] In 1949 het die Amerikaanse biochemici Morris Friedkin en Albert L. Lehninger bewys dat NADH metaboliese weë soos die sitroensuursiklus met die sintese van ATP in oksidatiewe fosforilering verbind het. [110] In 1958 het Jack Preiss en Philip Handler ontdek die tussenprodukte en ensieme betrokke by die biosintese van NAD + [111] [112] reddingsintese van nikotiensuur word die Preiss-Handler-weg genoem. In 2004 het Charles Brenner en medewerkers die nikotinamied-ribosiedkinase-weg na NAD + ontbloot. [113]

Die nie-redoksrolle van NAD(P) is later ontdek. [2] Die eerste wat geïdentifiseer is, was die gebruik van NAD + as die ADP-ribose-skenker in ADP-ribosileringsreaksies, wat in die vroeë 1960's waargeneem is. [114] Studies in die 1980's en 1990's het die aktiwiteite van NAD + en NADP + metaboliete in selseine aan die lig gebring - soos die werking van sikliese ADP-ribose, wat in 1987 ontdek is. [115]

Die metabolisme van NAD + het 'n gebied van intense navorsing in die 21ste eeu gebly, met belangstelling verhoog na die ontdekking van die NAD + -afhanklike proteïen deasetylase genoem sirtuins in 2000, deur Shin-ichiro Imai en kollegas in die laboratorium van Leonard P. Guarente . [116] In 2009 het Imai die "NAD World"-hipotese voorgestel dat sleutelreguleerders van veroudering en langlewendheid by soogdiere sirtuin 1 en die primêre NAD + sintetiseringsensiem nikotinamied-fosforibosieltransferase (NAMPT) is. [117] In 2016 het Imai sy hipotese uitgebrei na "NAD World 2.0" wat postuleer dat ekstrasellulêre NAMPT vanaf vetweefsel NAD + in die hipotalamus (die beheersentrum) handhaaf in samewerking met miokiene van skeletspierselle. [118]


Inleiding tot mobiele energiedraers

Afdeling Opsomming

Energie word op 'n verskeidenheid maniere rondbeweeg en binne die sel oorgedra. Een kritieke meganisme wat die natuur ontwikkel het, is die gebruik van herwinbare molekulêre energiedraers. Alhoewel daar verskeie groot herwinbare energiedraers is, deel hulle almal 'n paar algemene funksionele kenmerke:

Eienskappe van sleutel sellulêre molekulêre energiedraers

  • Ons dink aan die energiedraers as bestaande in "poele" van beskikbare draers. 'n Mens kan, na analogie, hierdie mobiele energiedraers analoog aan die afleweringsvoertuie van pakkiedraers beskou - die maatskappy het 'n sekere "pool" beskikbare voertuie op enige tydstip om op te tel en aflewerings te doen.
  • Elke individuele draer in die swembad kan in een van verskeie afsonderlike toestande bestaan: dit dra óf 'n "lading" energie, 'n fraksionele lading, óf is "leeg". Die molekule kan tussen "gelaai" en leeg omskakel en kan dus herwin word. Weereens na analogie kan die afleweringsvoertuie óf pakkies dra óf leeg wees en wissel tussen hierdie toestande.
  • Die balans of verhouding in die poel tussen "gelaaide" en "ontlaaide" draers is belangrik vir sellulêre funksie, word deur die sel gereguleer en kan dikwels vir ons iets vertel oor die toestand van 'n sel. Net so hou 'n pakkie karweierdiens fyn dop hoe vol of leeg hul afleweringsvoertuie is - as hulle te vol is kan daar onvoldoende "leë" vragmotors wees om nuwe pakkies op te tel as dit te leeg is, besigheid moet nie goed gaan nie of dit is afgesluit is daar 'n gepaste balans vir verskillende situasies.

In hierdie kursus sal ons twee hooftipes molekulêre herwinbare energiedraers ondersoek: (1) nikotinamied adenien dinukleotied (NAD+), 'n nabye familielid nikotinamied adenien dinukleotied fosfaat (NADP + ), en flavien adenien dinukleotied (FAD 2+) en (2) nukleotied mono-, di- en trifosfate, met besondere aandag aan adenosientrifosfaat (ATP). Elkeen van hierdie twee tipes molekules is betrokke by energie-oordrag wat verskillende klasse chemiese reaksies behels. Dit is interessant dat terwyl een klas draer elektrone (en energie) lewer, die ander fosfate (en energie) lewer, maar albei bevat 'n adeniennukleotied(e). Miskien was adeniennukleotiede 'n belangrike deel van die vroeë lewe? Kyk na die "RNA wêreld" teorie.

Redokschemie en elektrondraers

Die oksidasie van, of verwydering van 'n elektron van, 'n molekule (of dit nou gepaard gaan met die verwydering van 'n gepaardgaande proton of nie) lei tot 'n verandering van vrye energie vir daardie molekule - materie, interne energie en entropie het alles verander in die proses . Net so verander die reduksie van (die wins van elektron op) 'n molekule ook sy vrye energie. Die grootte van verandering in vrye energie en die rigting daarvan (positief of negatief) vir 'n redoksreaksie bepaal die spontaneïteit van die reaksie en hoeveel energie oorgedra word. In biologiese stelsels, waar baie energie-oordrag deur redoksreaksies plaasvind, is dit belangrik om te verstaan ​​hoe hierdie reaksies bemiddel word en begin idees of hipoteses oorweeg waarom hierdie reaksies in baie gevalle deur 'n klein familie elektrondraers bemiddel word. .

Moontlike bespreking: Verbind die verbranding van sellulose ('n suikerpolimeer) met die laaste paragraaf hierbo. Wat het daardie demonstrasie te doen met ons komende bespreking oor redoksdraers. Daar is reeds 'n paar melding hierbo - kan jy dit vind?

Moontlike bespreking: Die probleem waarna in die vorige besprekingsvraag verwys is, is 'n goeie plek om die ontwerpuitdagingsrubriek te begin inbring. As jy onthou, vra die eerste stap van die rubriek dat jy 'n probleem of vraag definieer. In hierdie geval, laat ons ons voorstel dat daar 'n probleem is om te definieer waarvoor die mobiele elektrondraers hieronder die Natuur gehelp het om op te los.

***--- Onthou evolusie stuur NIE ingenieursoplossings vir probleme aan nie, maar in retrospek kan ons ons verbeelding en logika gebruik om af te lei dat dit wat ons sien bewaar deur natuurlike seleksie 'n selektiewe voordeel verskaf het omdat die natuurlike innovasie 'n probleem " opgelos" het wat sukses beperk het . ---***

Ontwerpuitdaging vir Redox-draers

  • Wat was 'n probleem(te) wat die evolusie van mobiele elektron/redoksdraers help oplos het?
  • Die volgende stap van die ontwerpuitdaging vra jou om kriteria vir suksesvolle oplossings te identifiseer. Wat is die kriteria vir sukses in die probleem wat jy geïdentifiseer het?
  • Stap 3 in die ontwerpuitdaging vra jou om moontlike oplossings te identifiseer. Wel, hier het die natuur 'n paar vir ons geïdentifiseer - ons oorweeg drie in die leesstuk hieronder. Dit lyk of die natuur gelukkig is om verskeie oplossings vir die probleem te hê.
  • Die voorlaaste stap van die ontwerpuitdagingsrubriek vra jou om die voorgestelde oplossings te evalueer teen die kriteria vir sukses. Dit behoort jou te laat dink/bespreek oor hoekom daar verskeie verskillende elektrondraers is? Is daar verskillende kriteria vir sukses? Los hulle elkeen effens verskillende probleme op? Wat dink jy? Wees op die uitkyk terwyl ons deur metabolisme gaan vir leidrade.

NAD + /H en FADH/H2

In lewende stelsels funksioneer 'n klein klas verbindings as elektronpendel: Hulle bind en dra elektrone tussen verbindings in verskillende metaboliese weë. Die belangrikste elektrondraers wat ons sal oorweeg, is afkomstig van die B-vitamiengroep en is afgeleides van nukleotiede. Hierdie verbindings kan beide gereduseer word (dit wil sê hulle aanvaar elektrone) of geoksideer word (hulle verloor elektrone) afhangende van die reduksiepotensiaal van 'n potensiële elektronskenker of -ontvanger waarheen hulle elektrone kan oordra na en van. Nikotinamied adenien dinukleotied (NAD + ) (die struktuur word hieronder getoon) is afgelei van vitamien B3, niasien. NAD + is the oxidized form of the molecule NADH is the reduced form of the molecule after it has accepted two electrons and a proton (which together are the equivalent of a hydrogen atom with an extra electron).

We are expecting you to know which is the oxidized and which is the reduced form of NAD+/NADH, and be able to recognize either form on-the-spot in the context of a chemical reaction.

NAD + can accept electrons from an organic molecule according to the general equation:

A bit of vocabulary review: When electrons are added to a compound, the compound is said to have been verminder. A compound that reduces another (donates electrons) is called a reducing agent. In the above equation, RH is a reducing agent, and NAD + is reduced to NADH. When electrons are removed from a compound, it becomes oxidized. A compound that oxidizes another is called an oksideermiddel. In the above equation, NAD+ is an oxidizing agent, and RH is oxidized to R.

You need to get this down! We will (a) test specifically on your ability to do so - as "easy" questions and (b) we will use the terms with the expectation that you know what they mean and can relate them to biochemical reactions correctly (in class and on tests).

You will also encounter a second variation of NAD + , NADP + . It is structurally very similar to NAD + but it contains an extra phosphate group and plays an important role in anabolic reactions such as photosynthesis. Another nucleotide-based electron carrier that you will also encounter in this course and beyond, flavin adenine dinucleotide (FAD + ) is derived from vitamin B2, ook genoem riboflavien. Sy verminderde vorm is FADH2. Learn to recognize these molecules as electron carriers as well.

The oxidized form of the electron carrier (NAD + ) is shown on the left and the reduced form (NADH) is shown on the right. Die stikstofbasis in NADH het nog een waterstofioon en nog twee elektrone as in NAD +.

NAD + is used by the cell to "pull" electrons off of compounds and to carry them to other locations within the cell, thus they are called elektrondraers. NAD + /H compounds are used in many of the metabolic processes we will discuss in this class. For example, in its oxidized form NAD + is used as a reactant in glycolysis and the TCA cycle, whereas in its reduced form (NADH) it is a reactant in fermentation and the electron transport chain (ETC). Each of these processes will be discussed in later modules.

Energy Story for a Redox Reaction

***As a rule of thumb, when we see NAD + /H as a reactant or product we know we are looking at a redox reaction.***

When NADH is a product and NAD + is a reactant we know that NAD + has become reduced (forming NADH) therefore the other reactant must have been the electron donor and become oxidized. The vice versa is also true. If NADH has become NAD + , then the other reactant must have gained electrons from NADH and become reduced.

This reaction shows the conversion of pyruvate to lactic acid coupled with the conversion of NADH to NAD + . Source: en.wikibooks.org/wiki/Structural_Biochemistry/Enzyme/sequential_reactions

In the figure above we see the reaction of pyruvate becoming lactic acid, coupled with the conversion of NADH into NAD+. This reaction is catalyzed by LDH. Using our 'rule of thumb' above, we categorize this reaction as a redox reaction. NADH is the reduced form of the electron carrier and NADH is converted into NAD + . This half of the reaction results in the oxidation of the electron carrier. Pyruvate is converted into lactic acid in this reaction. Both of these sugars are negatively charged so it would be difficult to see which compound is more reduced using the charges of the compounds. However, we know that pyruvate has become reduced to form lactic acid because this conversion is coupled to the oxidation of NADH into NAD + . But how can we tell that lactic acid is more reduced than pyruvate? The answer is to look at the carbon-hydrogen bonds in both compounds. As electrons are transferred, they are often accompanied by a hydrogen atom. There are a total of 3 C-H bonds in pyruvate and there are a total of 4 C-H bonds in lactic acid. When we compare these two compounds in the before and after state, we see that lactic acid has one more C-H bond, therefore, lactic acid is more reduced than pyruvate. Note also lactic acid it has picked up 2 complete hydrogen atoms (and the source of these was. ). This holds true for multiple compounds. For example, the figure below, you should be able to rank the compounds from most to least reduced using the C-H bonds as your guide.

Above are a series of compounds than can be ranked or reorganized from most to least reduced. Compare the number of C-H bonds in each compound. Carbon dioxide has no C-H bonds and is the most oxidized form of carbon we will discuss in this class. Answer: Most reduced is methane (compound 3), then methanol (4), formaldehyde (1), carboxylic acid (2), and finally carbon dioxide (5).

This reaction shows the conversion of G3P, Pi, NAD+ into NADH and 1,3-BPG. This reaction is catalyzed by Glyceraldehyde-3-phosphate dehydrogenase.

Energy story for the reaction catalyzed by Glyceraldehyde-3-phosphate dehydrogenase:

Let's make an energy story for the reaction above.

First, let's characterize the reactants and products. The reactants are Glyceraldehyde-3-phosphate (a carbon compound), Pi (inorganic phosphate) and NAD + . These three reactants enter into a chemical reaction to produce two products, NADH and 1,3-Bisphosphoglycerate. If you look closely you can see that the 1,3-BPG contains two phosphates. This is important when we are double checking that no mass has been lost. There are two phosphates in the reactants so there need to be two phosphates in the products (conservation of mass!). You can double check that all the other atoms are also accounted for. The enzyme that catalyzes this reaction is called Glyceraldehyde-3-phosphate dehydrogenase. The standard free energy change of this reaction is

6.3 kJ/mol so under standard conditions we can say that the free energy of the products is higher than that of the reactants and that this reaction is not spontaneous under standard conditions.

What can we say about this reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase?

This is a redox reaction. We know that because we have produced a reduced electron carrier (NADH) as a product and NAD + is a reactant. Where did the electron come from to make NADH? The electron must have come from the other reactant (the carbon compound).

Recommended discussion: We will spend some time examining the reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase in more detail as we move through the lectures and text. The first thing to discuss here is that the figure above is a highly simplified or condensed version of the steps that take place - one could in fact break that reaction above into TWO conceptual reactions. Can you imagine what those two "subreactions" might be? Bespreek onder mekaar.

Recommended discussion: The text above notes that the standard change in free energy for this complex reaction is

+6.3 kJ/mol. Under standard conditions this reaction is NOT spontaneous. However, this is one of the key reactions in the oxidation of glucose. It needs to GO in the cell. The questions are: why is it important to note things like "standard change of free energy" or "under standard conditions" when reporting that &DeltaG°? What could possibly be going on in the cell to make what is under standard conditions an endergonic reaction "go" under real-life conditions?


Why does NAD+ become reduced if it gains a hydrogen proton? - Biologie

DEFINITIONS OF OXIDATION AND REDUCTION (REDOX)

This page looks at the various definitions of oxidation and reduction (redox) in terms of the transfer of oxygen, hydrogen and electrons. It also explains the terms oxidising agent and reducing agent.

Oxidation and reduction in terms of oxygen transfer

Oxidation is gain of oxygen.

Reduction is loss of oxygen.

For example, in the extraction of iron from its ore:

Because both rooiuction and osidation are going on side-by-side, this is known as a redoks reaksie.

Oxidising and reducing agents

An oxidising agent is substance which oxidises something else. In the above example, the iron(III) oxide is the oxidising agent.

A reducing agent reduces something else. In the equation, the carbon monoxide is the reducing agent.

Oxidising agents give oxygen to another substance.

Reducing agents remove oxygen from another substance.

Oxidation and reduction in terms of hydrogen transfer

These are old definitions which aren't used very much nowadays. The most likely place you will come across them is in organic chemistry.

Oxidation is loss of hydrogen.

Reduction is gain of hydrogen.

Notice that these are exactly the opposite of the oxygen definitions.

For example, ethanol can be oxidised to ethanal:

You would need to use an oxidising agent to remove the hydrogen from the ethanol. A commonly used oxidising agent is potassium dichromate(VI) solution acidified with dilute sulphuric acid.

Let wel: The equation for this is rather complicated for this introductory page. If you are interested, you will find a similar example (ethanol to ethanoic acid) on the page dealing with writing equations for redox reactions.

Ethanal can also be reduced back to ethanol again by adding hydrogen to it. A possible reducing agent is sodium tetrahydridoborate, NaBH4. Again the equation is too complicated to be worth bothering about at this point.

An update on oxidising and reducing agents

Oxidising agents give oxygen to another substance or remove hydrogen from it.

Reducing agents remove oxygen from another substance or give hydrogen to it.

Oxidation and reduction in terms of electron transfer

This is easily the most important use of the terms oxidation and reduction at A' level.

Oxidation is loss of electrons.

Reduction is gain of electrons.

It is essential that you remember these definitions. There is a very easy way to do this. As long as you remember that you are talking about electron transfer:

The equation shows a simple redox reaction which can obviously be described in terms of oxygen transfer.

Copper(II) oxide and magnesium oxide are both ionic. The metals obviously aren't. If you rewrite this as an ionic equation, it turns out that the oxide ions are spectator ions and you are left with:

A last comment on oxidising and reducing agents

If you look at the equation above, the magnesium is reducing the copper(II) ions by giving them electrons to neutralise the charge. Magnesium is a reducing agent.

Looking at it the other way round, the copper(II) ions are removing electrons from the magnesium to create the magnesium ions. The copper(II) ions are acting as an oxidising agent.

This is potentially very confusing if you try to learn both what oxidation and reduction mean in terms of electron transfer, and also learn definitions of oxidising and reducing agents in the same terms.

Personally, I would recommend that you work it out if you need it. The argument (going on inside your head) would go like this if you wanted to know, for example, what an oxidising agent did in terms of electrons:

An oxidising agent oxidises something else.

Oxidation is loss of electrons (OIL RIG).

That means that an oxidising agent takes electrons from that other substance.

So an oxidising agent must gain electrons.

Or you could think it out like this:

An oxidising agent oxidises something else.

That means that the oxidising agent must be being reduced.

Reduction is gain of electrons (OIL RIG).

So an oxidising agent must gain electrons.

Understanding is a lot safer than thoughtless learning!

Questions to test your understanding

If this is the first set of questions you have done, please read the introductory page before you start. You will need to use the BACK BUTTON on your browser to come back here afterwards.


Cellular respiration results when chemical redox reactions transfer electrons

In metabolic reactions, the most free energy is released by chemical reactions known as redox reactions. Redox reactions transfer electrons between molecules. A molecule that gains electrons is verminder a molecule that loses electrons is oxidized, which is how “redox” gets its name. You can use the phrase “OIL RIG” to remember that Oxidation Is Loss, Reduction Is Gain. Different molecules have different tendencies to gain electrons, called the redox potential. A redox reaction between a pair of molecules with a large difference in redox potential results in a large release of free energy.

Cellular energy metabolism features a series of redox reactions. Heterotrophs oxidize (take electrons from) organic molecules (food) and give those electrons to an electron carrier molecule, called NAD+ (in the oxidized form) that accepts electrons from food to become NADH (the reduced form). NADH then cycles back to NAD+ by giving electrons to (reducing) an electron acceptor protein in a membrane, thus becoming oxidized to NAD+ again. In the membrane, the electrons are transferred down an electron transport chain, consisting of a series of membrane proteins and molecules with increasing redox potential. Components of the electron transport chain use the sequential releases of free energy to pump protons across the membrane against their electrochemical gradient.

The electron transport chain, part of cellular respiration, transfers electrons from donors to acceptors,operating in the cell membrane. The process generates an gradient of protons, in the form of hydrogen ions, outside the membrane. [Image modified by C. Spencer from a Wikimedia image by Fvasconcellos in the public domain.]

Cellular respiration is the cascade of electrons transfers (redox reactions) that culminates in the reduction of the terminal electron acceptor. The amount of energy released by these redox reactions, and thus the amount of energy available for ATP synthesis, depends on the redox potential of the terminal electron acceptor. Suurstof (O2) has the greatest redox potential, and thus respiration in an oxygen-rich environment like earth’s current environment results in the most ATP synthesized. Bacteria and Archaea (and some Eukarya) can use other terminal electron acceptors with lower redox potential when oxygen is not available type of respiration produces less ATP.


Die elektronvervoerketting

Firstly, electrons enter the transport chain through delivery by electron carriers NADH en FADH. These reduced electron carriers from the previous steps of cellular respiration transfer their electrons to molecules near the beginning of the transport chain. Following loss of their electrons, they are oxidised into NAD+ en FADH when can then be herwin to other steps of respiration.

More specifically, NADH starts the process by depositing its electrons at Kompleks ek, turning into NAD+ and releasing a proton into the matrix. FADH2 is not as good at donating electrons as NADH (its electrons are at a lower energy level), so it cannot transfer its electrons to Complex I. Instead, FADH2 deposits electrons at Complex II. It is then reduced to FAD and releases 2 hydrogen atoms.

The electrons from Complexes I and II are then passed to another carrier, ubiquinone (Q). Q (now in the reduced form QH2) is a mobile electron carrier, free to travel through the membrane. Q transports the electrons to Kompleks III. As electrons pass through Complex III, more hydrogen ions are pumped across the membrane, and the electrons are passed to cytochrome C, which is also mobile and free to pass through the membrane.

Cytochrome C passes the electrons to Kompleks IV. Complex IV passes the electrons to suurstof, the terminal electron acceptor. Oxygen is split into two oxygen atoms, and accepts H+ from the matrix to form water. It takes two electrons, one oxygen (1/2 O2 molecule), and 2 H+ ions to form one water molecule. Complexes I, III, and IV use the energy released from electrons moving from higher to lower energy levels to move protons out of the matrix and into the intermembrane space. This generates a proton gradient.


Gain and Loss of Electrons

The original view of oxidation and reduction is that of adding or removing oxygen. An alternative view is to describe oxidation as the losing of electrons and reduction as the gaining of electrons. One example in which this approach is of value is in the high temperature reaction of lead dioxide .

In this reaction the lead atoms gain an electron (reduction) while the oxygen loses electrons (oxidation).

This electron view of oxidation and reduction helps you deal with the fact that "oxidation" can occur even when there is no oxygen! The definition of redox reactions is extended to include other reactions with nonmetals such as chlorine and bromine. For example, the reaction

Magnesium loses electrons and is therefore said to be "oxidized", whereas the chlorines gain electrons and are said to be reduced. Another way to judge that the chlorine has been reduced is the fact that the charge on the atoms is made more negative, or reduced. Treating that charge as an "oxidation number" is another way to characterize oxidation and reduction.

The view of oxidation and reduction as the loss and gain of electrons, respectively, is particularly appropriate for discussing reactions in electrochemical cells. For example, in the zinc-copper cell, the oxidation and reduction half-reactions are


Consider the reaction between zinc metal and hydrochloric acid.

If this reaction where broken down to the ion level:

First, look at what happens to the zinc atoms. Initially, we have a neutral zinc atom. As the reaction progresses, the zinc atom loses two electrons to become a Zn 2+ ion.

The zinc was oxidized into Zn 2+ ions. This reaction is an oxidation reaction.

The second part of this reaction involves the hydrogen ions. The hydrogen ions are gaining electrons and bonding together to form dihydrogen gas.

The hydrogen ions each gained an electron to form the neutrally charged hydrogen gas. The hydrogen ions are said to be reduced and the reaction is a reduction reaction. Since both processes are going on at the same time, the initial reaction is called an oxidation-reduction reaction. This type of reaction is also called a redox reaction (REDuction/OXidation).


The nature of the respiratory chain

Four types of hydrogen or electron carriers are known to participate in the respiratory chain, in which they serve to transfer two reducing equivalents (2H) from reduced substrate (AH.2) to molecular oxygen (reaction [49]) the products are the oxidized substrate (A) en water (H.2O).

The carriers are NAD + and, less frequently, NADP + the flavoproteins FAD and FMN (flavin mononucleotide) ubiquinone (or coenzyme Q) and several types of cytochromes. Each carrier has an oxidized and reduced form (e.g., FAD and FADH2, respectively), the two forms constituting an oxidation-reduction, or redox, couple. Within the respiratory chain, each redox couple undergoes cyclic oxidation-reduction i.e., the oxidized component of the couple accepts reducing equivalents from either a substrate or a reduced carrier preceding it in the series and in turn donates these reducing equivalents to the next oxidized carrier in the sequence. Reducing equivalents are thus transferred from substrates to molecular oxygen by a number of sequential redox reactions.

Most oxidizable catabolic intermediates initially undergo a dehydrogenation reaction, during which a dehydrogenase enzyme transfers the equivalent of a hydride ion (H + + 2e − , with e − representing an electron) to its coenzyme, either NAD + or NADP + . The reduced NAD + (or NADP + ) thus produced (usually written as NADH + H + or NADPH + H + ) diffuses to the membrane-bound respiratory chain to be oxidized by an enzyme known as NADH dehydrogenase the enzyme has as its coenzyme FMN. There is no corresponding NADPH dehydrogenase in mammalian mitochondria instead, the reducing equivalents of NADPH + H + are transferred to NAD + in a reaction catalyzed by a transhydrogenase enzyme, with the products being reduced NADH + H + and NADP + . A few substrates (e.g., acyl coenzyme A and succinate reactions [22] and [44]) bypass this reaction and instead undergo immediate dehydrogenation by specific membrane-bound dehydrogenase enzymes. During the reaction, the coenzyme FAD accepts two hydrogen atoms and two electrons (2H + 2e − ). The reduced flavoproteins (i.e., FMNH2 and FADH2) donate their two hydrogen atoms to the lipid carrier ubiquinone, which is thus reduced.

The fourth type of carrier, the cytochromes, consists of hemoproteins—i.e., proteins with a nonprotein component, or prosthetic group, called heme (or a derivative of heme), which is an iron-containing pigment molecule. The iron atom in the prosthetic group is able to carry one electron and oscillates between the oxidized, or ferric (Fe 3+ ), and the reduced, or ferrous (Fe 2+ ), forms. The five cytochromes present in the mammalian respiratory chain, designated cytochromes b, c1, c, a, en a3, act in sequence between ubiquinone and molecular oxygen. The terminal cytochrome of this sequence (a3, also known as cytochrome oxidase) is able to donate electrons to oxygen rather than to another electron carrier a3 is also the site of action of two substances that inhibit the respiratory chain, potassium cyanide and carbon monoxide. Special Fe-S complexes play a role in the activity of NADH dehydrogenase and succinate dehydrogenase.

In each redox couple, the reduced form has a tendency to lose reducing equivalents (i.e., to act as an electron or hydrogen donor) similarly, the oxidized form has a tendency to gain reducing equivalents (i.e., to act as an electron or hydrogen acceptor). The oxidation-reduction characteristics of each couple can be determined experimentally under well-defined standard conditions. The value thus obtained is the standard oxidation-reduction (redox) potential (Eó). Values for respiratory chain carriers range from Eó = −320 millivolts (one millivolt = 0.001 volt) for NAD + /reduced NAD + to Eó = +820 millivolts for 1 /2 O2/H2O the values for intermediate carriers lie between. Reduced NAD + is the most electronegative carrier, oxygen the most electropositive acceptor. During respiration, reducing equivalents undergo stepwise transfer from the reduced form of the most electronegative carrier (reduced NAD + ) to the oxidized form of the most electropositive couple (oxygen). Each step is accompanied by a decline in standard free energy (ΔG′) proportional to the difference in the standard redox potentials (ΔE0) of the two carriers involved.

Overall oxidation of reduced NAD + by oxygen (ΔE0 = +1,140 millivolts) is accompanied by the liberation of free energy (ΔG′ = −52.4 kilocalories per mole). In theory, this energy is sufficient to allow the synthesis of six or seven molecules of ATP. In the cell, however, this synthesis of ATP, called oxidative phosphorylation, proceeds with an efficiency of about 46 percent. Thus, only three molecules of ATP are produced per atom of oxygen consumed—this being the so-called P/2e - , P/O, or ADP/O ratio. The energy that is not conserved as ATP is lost as heat. The oxidation of succinate by molecular oxygen (ΔE0 = +790 millivolts), which is accompanied by a smaller liberation of free energy (ΔG′ = −36.5 kilocalories per mole), yields only two molecules of ATP per atom of oxygen consumed (P/O = 2).


Kyk die video: What is NAD+? (September 2022).