Zaloge metaboličnih goriv
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1 Osnovne naloge metabolizma Integracija metabolizma 1. Zagotavljanje metaboličnih goriv vsem celicam 2. Odstranjevanje odpadnih produktov 3. Zaščita 4. Integracija prof.dr.m.žakelj-mavrič Zagotavljanje metaboličnih goriv vsem celicam Funkcijo opravljajo: maščevje, jetra, mišice, tanko črevo, pankreas Pomembna metabolična goriva: glukoza, maščobne kisline, ketonske spojine, AK Poleg tega potrebujemo še vitamine, ione (Na +, K +, Ca 2+, Mg 2+, Zn 2+...), vodo Zaloge metaboličnih goriv Metabolična goriva pridobimo s hrano, iz endogenih zalog ali pa jih sintetiziramo sami iz drugih goriv (ketonske spojine) 400 1
2 Stopnje katabolizma Pridobivanje energije iz metaboličnih goriv je razdeljeno na tri stopnje. V prisotnosti kisika in funkcionalnih mitohondrijev poteka oksidacija metaboličnih goriv SH 2 + NAD + S + NADH + H + (FAD) (FADH 2 ) NADH + H + + 1/2 O 2 NAD + + H 2 0 (FADH 2 ) (FAD) Oksidativna fosforilacija Pridobivanje ATP iz metaboličnih goriv NADH + H + + 3ADP + 3 P i +1/2 O 2 > NAD + + H 2 O + 3 ATP + 3H 2 O 1 MK, Glc,(AK), ketonska telesa AcCoA Kaj pa če ni kisika ali funkcionalnih mitohondrijev? 2NAD + glukoza 2NAD + 2NADH + 2H + 2piruvat V tem slučaju celice pridobivajo energijo z anaerobno glikolizo 2laktat Anaerobna glikoliza lahko predstavlja izhod v sili!!! 2
3 Prekurzorji za biosinteze Metabolične poti Glikoliza in citratni ciklus dajeta prekurzorje za sintezo številnih biomolekul JETRA pentoza-p pentoze glukoza-6-p glikogen acetil-coa piruvat laktat maščobe FAT CO 2 Poiščite razlike med jetri, mišicami in maščevjem! MOŽGANI ERITROCIT glukoza pentoza-p pentoze glukoza-6-p pentoza-p pentoze glukoza-6p acetil-coa piruvat piruvat CO 2 Kateri procesi omogočajo pridobivanje energije iz Glc v možganih? laktat laktat 3
4 Katere skupne intermediate še poznamo? fosfatidat Kaj pa HMG-CoA in karbamoilfosfat? Od česa zavisi, po kateri poti se usmeri metabolit????? Odstranjevanje odpadnih produktov Zaščita Funkcijo opravljajo: jetra, ledvica.. Odpadni produkti: npr. sečnina, sečna kislina, bilirubin, ksenobiotiki, CO 2... Pri tej vlogi sodelujejo: mišice, kri (sistem za strjevanje krvi), koža in sluznice, imunski sistem... jetra in ledvica (detoksifikacija in izločanje npr. NH 3, ksenobiotikov) Integracija Integracija ob stresu-os hipotalamus-hipofiza-adrenalka Povezava centralnega živčevja z deli telesa preko živčevja in s pomočjo hormonov. Pri tej nalogi sodelujejo centralno živčevje, kri, pankreas... 4
5 Integracija ob stresu-os hipotalamus-hipofiza-adrenalka Osnovne naloge metabolizma 1. Zagotavljanje metaboličnih goriv vsem celicam 2. Odstranjevanje odpadnih produktov 3. Zaščita 4. Integracija Odziv metabolizma na različna prehrambena in hormonska stanja Metabolični procesi v stanju dobre prehranjenosti Metabolične povezave v stanju dobre prehranjenosti Odziv metabolizma na različna prehrambena in hormonska stanja 5
6 Spremembe v koncentracijah metaboličnih goriv med stradanjem Metabolične povezave ob podaljšanem stradanju Metabolični procesi ob stradanju Po cca 60 dneh se začno porabljati pomembni proteini, npr. proteini srčne mišice in nastopi smrt. Primerjava metabolizma Metabolična goriva in telesna aktivnost A)v času dobre hranjenosti B) ob podaljšanem stradanju 6
7 Metabolična goriva in telesna aktivnost Hitrost sinteze ATP v primerjavi s sposobnostjo vzdrževanja maksimalne mišične aktivnosti sprint Miokinaza!!!! Uravnavanje metabolizma glukoze med telesno aktivnostjo Med aktivnostjo se poveča izločanje glukagona, ki v jetrih omogoči proces glikogenolize Adrenalin in noradrenalin dodatno stimulirata glikogenolizo Raven kortizola se med vadbo tudi poveča, sproščene AK iz procesa proteolize služijo kot substrati za glukoneogenezo Kortizol, adrenalin in NE stimulirajo metabolizem MK Spremembe v konc. hormonov so odvisne od vrste in trajanja aktivnosti, treniranosti... Sproščeni hormoni omogočijo uravnavanje metaboličnih procesov na ravni organizma - omogočajo integracijo metaboličnih procesov med celicami in organi (npr. hormoni v jetrih stimulirajo sintezo glukoze,ki jo porabijo mišice). Na ravni celice poteka prilagoditev glede na razmere v celici- npr. uravnavanje celičnega metabolizma glede na energijsko stanje v celici - nastanek ATP v skladu s potrebami po ATP 7
8 vezava z regulatornim proteinom prisotnost encima v določenem celičnem razdelku Smo si podobni ali se razlikujemo???? Kako je z našimi metaboličnimi potmi?????? sinteza ENCIM razgradnja uravnavanje z alosteričnimi modulatorji uravnavanje s kovalentno modifikacijo Izražanje individualnosti Metabolomika Geni Individualnost Okolje sprememba poškodba... metaboliti filtracija resorpcija redčenje koncentracija prstni odtis metabolitov Porast koncentracije celičnih encimov (še( e posebej značilnih izoencimov) v krvi ima diagnostičen pomen (AST) (ALT) Številne bolezni so posledica sprememb v strukturi biomolekul (npr. DNA), množini biomolekul ali motenj v pomembnih biokemijskih reakcijah ali procesih. Poznavanje vzrokov bolezni lahko omogoči diagnostiko bolezni in pravilen tretma bolnika ( npr. diagnostika na osnovi metabolitov fenilalanina in pravilna dieta pri fenilketonuriji) 8
9 Uporaba inhibitorjev 1. Nekateri inhibitorji procesov pri človeku so hudi strupi, uporaba smrtno nevarna (npr. CO) (?) 2. Druge inhibitorje človeških encimov uporabljamo kot zdravila (npr. statini inhibirajo HMG-CoA-reduktazo, aspirin inhibira COX) 3. Inhibitorji lahko selektivno inhibirajo proces pri bakterijah (najprimernejše mesto delovanja proces, ki pri človeku ne poteka, kot npr. biosinteza celične stene bakterij oz. proces, ki se pri človeku razlikuje od bakterijskega) Sept. 30, 2004: Merck pulls popular pain drug due to risks of heart attacks COX-1 konstitutivna Cox-1 / Cox-2 Stališče izpred nekaj let arahidonska k. COX-2 inducibilna dobri prostaglandini slabi prostaglandini zaščita GI akt. trombocitov funkcija ledvic vnetje bolečina vročina COX-1 konstitutivna (izjeme!) Cox-1 / Cox-2 Ugotovitve danes arahidonska k. COX-2 inducibilna (izjeme!) Hvala za pozornost! prostaglandini zaščita GI akt. trombocitov funkcija ledvic prostaglandini patološki vnetje bolečina vročina fiziološki funkcija ledvic žilni popravilo tkiv Vprašanja naslovite na: Marija.Zakelj-Mavric@mf.uni-lj.si ali Marijo Žakelj-Mavrič (osebno!) 9
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