H4. Acetyl-CoA-productiemechanismen en de
Krebscyclus
1. Respiratie
= aerobe vorm v metabolisme
Pyruvaat geoxideerd -> H2O & CO2 in aerobe omst
-> 3 stadia
1. Organische brandstofmolec, glucose, vetz, Bep AZ & ethanol oxideren
-> 2-C-fragmenten in vorm acetylgroep
2. Acetylgroepen enzymatisch geoxideerd -> CO2 in Krebscyclus:
E vrijgesteld = NADH & FADH2
3. Co-enz zelf gereduc: p+ & e- afgeven
e- getransfereerd -> O2 : ATP geconserveerd = ‘oxidatieve fosforylatie’
2. Acetyl-CoA-productiemechanismen
Aanmaak van Acetyl-CoA uit pyruvaat
Pyruvaat geoxideerd->acetyl-CoA & CO2 —> PDH-complex
= cluster 3 enz in mitoch EU & cytosol PRO
= multi-enzcomplex
= 5 cofactoren
=geregelde metabole ux
= prototype :
Pyruvaat wordt geoxideerd tot acetyl-CoA en CO2
Het PDH-complex heeft 5 co-enzymen nodig
- TPP
- FAD
- CoA
- NAD
- lipoïnezuur
4 vitaminen
- Thiamine in TPP
- Ribo avine in FAD
- Niacine in NAD
- Pantotheenzuur in CoA
Co-enzym A : reactieve thiolgroep = acylcarrier
-> acrylgroepen binden cov aan thiolgroepen => thio-esters
Thiaminepyrofosfaat
functioneel deel = thiazoliumring : zure p+ op C2
Lipoïnezuur
2 thiolgroepen reversibele oxidatie -> Sα-brug
1 Metabolisme & metabole regeling Julie De Wit
fl fl
, vrijdag 22 april 2022
Werking van het PDH-Complex (5 stappen)
Stap 1:
TPP dissoc -> carbanion: bindt gemak aan carbonylgroep pyruvaat
posi geladen ring TPP = e-aantrekker
=>stabilisatie neg lading
promonering => hydroxyethyl-TPP
Pyruvaat + TPP -> hydroxyethylTPP
De B-oxidatie van de vetzuren
Cellen verkrijgen vetzuurbrandsto en
—>vetten gegeten in voeding
—> opgestapeld in cellen als lipidedruppels
—> gensynth in orgaan vo export -> ander orgaan
Hormonen detecteren: behoefte metabole E => vetz gemobiliseerd uit vetweefsel
1. Hormonen adrenaline & glucagon activeren enz adenylcyclase
2. Adenylcyclase produc cAMP
3. cAMP-afh kinase fosforyleert & activeert triglyceride lipase
4. Triglyceride lipase katalyseert hydrolysering esterbindingen in triglyceriden
5. Vetz binden aan eiw serum albumine -> andere weefsels
Enz B-oxidatie in mitochondriale matrix
Vetzuur valt aan op ATP => ° vetzuur-adenylaat en 2 Pi
Thiolgroep van CoA nucleo ele aanval, gekatalyseerd —> vetzuur-acetyl CoA synthetase,
op C => ° acetyl-CoA
B-oxidatie = progressieve oxidatieve verwijdering 2 C-units in vorm v acetyl-CoA
2 Metabolisme & metabole regeling Julie De Wit
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