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Samenvatting Biochemie

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  • Course
  • Celbiologie partim medische biochemie
  • Institution
  • Universiteit Antwerpen (UA)
  • Book
  • Harpers Illustrated Biochemistry 30th Edition

Deze samenvatting is gebaseerd op de hoorcolleges medische biochemie van prof. dr. L. Roosens. Er wordt vaak gebruik gemaakt van de metabole kaart van Stanford en van de cursus 'Harpers illustrated biochemistry'. Dit geeft een mooi geheel van de te kennen leerstof voor het tentamen.

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  • De hoofdstukken die in de colleges aan bod kwamen.
  • October 29, 2020
  • 113
  • 2019/2020
  • Summary

Subjects

  • geneeskunde
  • bachelor
  • biochemie
  • medische biochemie
  • metabole pathways
  • metabolisme
  • ua
  • universiteit antwerpen

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2019-2020 Samenvatting
biochemie




Kjell Van Rompa
1BA GENEESKUNDE

,1

,Inhoudsopgave
Inleidende hoofdstukken ................................................................................................... 8
Bio-energetica ............................................................................................................................................. 8
Rol van ATP ...................................................................................................................................................................... 8
Endergone en exergone reacties ...................................................................................................................................................... 8
Vrije energie ..................................................................................................................................................................................... 8
Koppeling endergone en exergone reacties ..................................................................................................................................... 8
Fysisch gekoppeld ............................................................................................................................................................................ 9
ATP ................................................................................................................................................................................................... 9
Biologische oxidatie ....................................................................................................................................................... 13
Algemeen ....................................................................................................................................................................................... 13
Elektronen doorgeven .................................................................................................................................................................... 13
Zuurstof als elektronendrager ........................................................................................................................................................ 14
Moleculen die hydriden kunnen ontvangen................................................................................................................................... 15
De respiratoire keten en oxidatieve fosforylatie ........................................................................................................... 16
Algemeen ....................................................................................................................................................................................... 16
Mitochondriën ............................................................................................................................................................................... 17
Hoeveelheid ATP ............................................................................................................................................................................ 17
Energierijke elektronendragers ...................................................................................................................................................... 17
Reis vd elektronen .......................................................................................................................................................................... 18
Link met vorming ATP .................................................................................................................................................................... 18
Regulatie ........................................................................................................................................................................................ 19
Toxische producten ........................................................................................................................................................................ 20
Transporters ................................................................................................................................................................................... 21

Enzymologie .............................................................................................................................................. 23
Werkingsmechanisme.................................................................................................................................................... 23
Algemeen ....................................................................................................................................................................................... 23
Enzymen ......................................................................................................................................................................................... 23
Enzymsubstraatcomplex ................................................................................................................................................................ 24
Cofactoren...................................................................................................................................................................................... 25
Isovormen ...................................................................................................................................................................................... 26
Enzymen opsporen ......................................................................................................................................................................... 26
Myocardinfarct diagnosticeren ...................................................................................................................................................... 27
Kinetiek .......................................................................................................................................................................... 28
Algemeen ....................................................................................................................................................................................... 28
Invloed op kinetiek ......................................................................................................................................................................... 28
Reactiesnelheid enzymen bekijken ................................................................................................................................................ 28
Michaelis-Menten enzymen ........................................................................................................................................................... 29
Allostere enzymen.......................................................................................................................................................................... 29
Regulatie ........................................................................................................................................................................ 30
Algemeen ....................................................................................................................................................................................... 30
Verschillende soorten regulatie ..................................................................................................................................................... 30
Inhibitie .......................................................................................................................................................................................... 32

Koolhydraatmetabolisme ................................................................................................ 33
Glycolyse en oxidatie van pyruvaat ........................................................................................................... 33
Overzicht ........................................................................................................................................................................ 33
Algemeen ....................................................................................................................................................................................... 33
Alternatieve richtingen voor de intermediairen ............................................................................................................................. 33
Weefselniveau: andere prioriteiten ............................................................................................................................................... 33
The fates of pyruvate ..................................................................................................................................................................... 34
Glycolyse en oxidatie pyruvaat ...................................................................................................................................... 34
Algemeen ....................................................................................................................................................................................... 34
Glucosetransporters ....................................................................................................................................................................... 34
Glucose is in de cel, wat nu? Reacties ............................................................................................................................................ 35
De 3 irreversibele reacties .............................................................................................................................................................. 36
Lactaat............................................................................................................................................................................................ 38
Zijsprong glycolyse ......................................................................................................................................................................... 39
Acetyl-CoA ...................................................................................................................................................................................... 39
Pyruvaatdehydrogenasecomplex (PDC) ......................................................................................................................................... 39
Andere hexosen ............................................................................................................................................................. 42
Fructose ......................................................................................................................................................................................... 42
Galactose........................................................................................................................................................................................ 43

Krebscyclus (TCA) ...................................................................................................................................... 44



2

, Voorafgaande (herhaling) .............................................................................................................................................. 44
Krebscyclus .................................................................................................................................................................... 44
Algemeen ....................................................................................................................................................................................... 44
Verloop........................................................................................................................................................................................... 45
GTP vs ATP ..................................................................................................................................................................................... 46
De amfibole pathway ..................................................................................................................................................... 46
Algemeen ....................................................................................................................................................................................... 46
Bepaalde pyruvaat evenwichten .................................................................................................................................................... 46
Anabole deel TCA ........................................................................................................................................................................... 47
Regulatie ........................................................................................................................................................................ 47

Gluconeogenese en controle glucosemetabolisme .................................................................................... 48
Algemeen doel ............................................................................................................................................................... 48
Postprandiaal ................................................................................................................................................................. 48
Glucosehomeostase....................................................................................................................................................... 49
Mechanismen................................................................................................................................................................................. 49
Hormonale interventie ingezoomd ................................................................................................................................................ 49
Andere hormoon: ACTH ................................................................................................................................................................. 50
Verloop .......................................................................................................................................................................... 50
Algemeen ....................................................................................................................................................................................... 50
Bypass 1: van pyruvaat tot fosfoenolpyruvaat ............................................................................................................................... 51
Bypass 2: van fructose-1,6-fosfaat tot fructose-6-fosfaat .............................................................................................................. 51
Bypass 3: van glucose-6-fosfaat tot glucose ................................................................................................................................... 51
Belangrijke enzymen ...................................................................................................................................................... 51
Pyruvaatcarboxylase (PC) ............................................................................................................................................................... 51
Fosfoenolpyruvaatcarboxykinase ................................................................................................................................................... 52
Fructose-1,6-bisfosfatase ............................................................................................................................................................... 52
Glucose-6-fosfatase........................................................................................................................................................................ 52
Redenen voor gluconeogenese...................................................................................................................................... 53
Pyruvaatcarboxylase deficiëntie .................................................................................................................................... 53
Andere bouwstenen dan lactaat .................................................................................................................................... 53
Glycerol als bouwsteen .................................................................................................................................................................. 53
Propionzuur als bouwsteen ............................................................................................................................................................ 54
Regulatie glycolyse/gluconeogenese ............................................................................................................................. 54
Algemeen ....................................................................................................................................................................................... 54
Pyruvaatkinase (PK) ........................................................................................................................................................................ 55
Fructose-2,6-bisfosfaat / PFK2-FBP2 .............................................................................................................................................. 55
Pyruvaatcarboxylase (PC) ............................................................................................................................................................... 56
Samenvattende afbeelding (alle regelstappen) .............................................................................................................................. 56
Lever als altruïst ............................................................................................................................................................. 56
Cori cyclus ...................................................................................................................................................................................... 56
Glucose-alanine cyclus ................................................................................................................................................................... 56

Glycogeenmetabolisme ............................................................................................................................. 57
Algemeen ....................................................................................................................................................................... 57
Structuur ........................................................................................................................................................................ 57
Glycogenese: mbv glycogeensynthase en branching enzyme ....................................................................................... 57
Glycogenolyse: mbv fosforylase en debranching enzyme ............................................................................................. 58
Vertakte ketens.............................................................................................................................................................. 58
Glucose-6-fosfatase in ER .............................................................................................................................................. 58
Regulatie ........................................................................................................................................................................ 59
Aandoeningen glycogeenmetabolisme .......................................................................................................................... 60
Metabole kaart .............................................................................................................................................................. 60

Hexosemonofosfaat shunt / pentosemonofosfaat pathway ...................................................................... 61
Redenen voor pentosemonofosfaat pathway ............................................................................................................... 61
Kenmerken..................................................................................................................................................................... 61
2 delen ........................................................................................................................................................................... 61
Eerste deel ..................................................................................................................................................................................... 61
Tweede deel ................................................................................................................................................................................... 62
Regulatie ........................................................................................................................................................................ 63
De pathway bij RBC ........................................................................................................................................................ 63

Ethanolmetabolisme ....................................................................................................... 64
Algemeen .................................................................................................................................................. 64
Te veel NADH............................................................................................................................................. 64



3

, Algemeen ....................................................................................................................................................................... 64
Glycolyse ........................................................................................................................................................................ 64
Krebscyclus .................................................................................................................................................................... 65
Gluconeogenese ............................................................................................................................................................ 65
Vetzuursynthese ............................................................................................................................................................ 65

Lipidenmetabolisme........................................................................................................ 66
Lipiden van fysiologisch belang.................................................................................................................. 66
Inleiding ......................................................................................................................................................................... 66
Vetzuren ........................................................................................................................................................................ 67
Inzoomen op verschillende subgroepen ........................................................................................................................ 67
Triglyceriden................................................................................................................................................................................... 67
Fosfolipiden .................................................................................................................................................................................... 68
Fosfosfingosiden/sfingolipiden ...................................................................................................................................................... 68
Glycolipiden/cerebrosiden ............................................................................................................................................................. 68
Lysosomale stapelingsziekten ........................................................................................................................................ 69
Steroïden ....................................................................................................................................................................... 69

Vetzuuroxidatie en ketogenese ................................................................................................................. 70
Algemeen ....................................................................................................................................................................... 70
Classificatie vd vetzuren ................................................................................................................................................ 70
Vetzuurafbraak .............................................................................................................................................................. 70
Carnitine ......................................................................................................................................................................................... 70
Vetzuurtransport naar het mitochondrion ..................................................................................................................................... 70
Vetzuurafbraak/bèta-oxidatie ........................................................................................................................................................ 71
Afbraak vetzuren met oneven vetzuurstaart.................................................................................................................................. 71
Afbraak van vetzuren met >20 C’s .................................................................................................................................................. 72
E-winst ........................................................................................................................................................................................... 72
Samenvattende afbeelding ............................................................................................................................................................ 73
Ketogenese .................................................................................................................................................................... 73
Algemeen ....................................................................................................................................................................................... 73
Proces............................................................................................................................................................................................. 73
Regulatie ........................................................................................................................................................................ 74
Algemeen ....................................................................................................................................................................................... 74
Lipolyse .......................................................................................................................................................................................... 74
Bèta-oxidatie .................................................................................................................................................................................. 74
Samenvattende afbeelding ............................................................................................................................................................ 75

Biosynthese van vetzuren en eicosanoïden ............................................................................................... 75
Vorming vetzuren .......................................................................................................................................................... 75
Algemeen ....................................................................................................................................................................................... 75
De novo synthese ........................................................................................................................................................................... 75
Energievragend proces ................................................................................................................................................................... 76
Proces in het geheel ....................................................................................................................................................................... 76
Verwerking palmitaat ..................................................................................................................................................................... 77
Samenvattende afbeelding ............................................................................................................................................................ 78
Vorming eicosanoïden ................................................................................................................................................... 78
Vorming triglyceriden .................................................................................................................................................... 78
Algemeen ....................................................................................................................................................................................... 78
Afbraak/lipolyse ............................................................................................................................................................................. 79
Aanmaak/lipogenese...................................................................................................................................................................... 79
Insuline ........................................................................................................................................................................................... 79
Vervoer in bloed ............................................................................................................................................................................. 79
Regulatie vetzuurmetabolisme ...................................................................................................................................................... 79
Bijkomende regelmechanisme door acetyl-CoA carboxylase ......................................................................................................... 80

Lipidentransport en -opslag ....................................................................................................................... 80
Lipoproteïnepartikels (LPP’s) ......................................................................................................................................... 80
Mechanismen ................................................................................................................................................................ 81
Vetopname uit voeding .................................................................................................................................................................. 81
De novo synthese vetzuren in lever ............................................................................................................................................... 82
Werking HDL .................................................................................................................................................................................. 82
Metabole aandoeningen ................................................................................................................................................................ 82
Verschil chylomicronen en VLDL-partikels ..................................................................................................................................... 82

Cholesterolsynthese .................................................................................................................................. 83
Mechanisme .................................................................................................................................................................. 83
Regulatie ........................................................................................................................................................................ 83



4

, Cholesterolbalans .......................................................................................................................................................... 83

Aminozuurmetabolisme .................................................................................................. 84
Biosynthese van aminozuren ..................................................................................................................... 84
Bouwstenen lichaam ..................................................................................................................................................... 84
Aminozuren ................................................................................................................................................................... 84
Algemeen ....................................................................................................................................................................................... 84
Essentieel/niet-essentieel .............................................................................................................................................................. 84
Onderverdeling volgens chemische kenmerken............................................................................................................................. 84
Aandoeningen ................................................................................................................................................................................ 85
Niet-essentiele AZ .......................................................................................................................................................... 85
12 AZ + 1C eenheid metabolisme ................................................................................................................................................... 85
Collageendeficiënties ..................................................................................................................................................................... 87
AZ-families ..................................................................................................................................................................................... 87
Vertakte essentiële AZ: leucine, valine, isoleucine ........................................................................................................ 88
Gebruik AZ in metabolisme............................................................................................................................................ 88

Katabolisme en aminogroep ...................................................................................................................... 89
AZ-balans in lichaam ...................................................................................................................................................... 89
Inflow: ............................................................................................................................................................................................ 89
Outflow: ......................................................................................................................................................................................... 89
N-balans in lichaam = belangrijk .................................................................................................................................... 89
Halwaardetijd/afbraak enzymen ................................................................................................................................... 89
Afbraak AZ ..................................................................................................................................................................... 90
Overblijvende aminogroep? ........................................................................................................................................................... 90
Proces............................................................................................................................................................................................. 90
Ammoniakintoxicatie/hyperammoniëmie ..................................................................................................................... 91

Katabolisme en C-skelet ............................................................................................................................ 92
Glucose-alanine-cyclus .................................................................................................................................................. 92
AZ afleiden naar intermediairen .................................................................................................................................... 92

Afgeleide structuren .................................................................................................................................. 94
Haem ............................................................................................................................................................................. 94
Algemeen ....................................................................................................................................................................................... 94
Haemsynthese................................................................................................................................................................................ 94
Afbraak porfirinering ...................................................................................................................................................................... 95
Porfyrie........................................................................................................................................................................................... 95
Glutathion ...................................................................................................................................................................... 96
Neurotransmitters ......................................................................................................................................................... 96
Tyrosine omzetten in neurotransmitters........................................................................................................................................ 96
Afbraak neurotransmitters ............................................................................................................................................................. 96
Glutamaat → GABA (gamma-aminoboterzuur) ............................................................................................................................. 96
Tryptofaan → aanmaak serotonine ............................................................................................................................................... 96

Nucleïnezuurmetabolisme ............................................................................................... 97
Nucleotiden ............................................................................................................................................... 97
Metabolisme ............................................................................................................................................. 97
Verschil de novo en salvage ........................................................................................................................................... 97
Biosynthese purine nucleotiden .................................................................................................................................... 97
De novo .......................................................................................................................................................................................... 97
Salvage ........................................................................................................................................................................................... 98
Regulatie ........................................................................................................................................................................ 98
De novo biosynthese pyrimidine nucleotiden ............................................................................................................... 99
RNA → DNA ................................................................................................................................................................... 99
Afbraak .......................................................................................................................................................................... 99
Purines ........................................................................................................................................................................................... 99
Pyrimidines................................................................................................................................................................................... 100
Aandoeningen .............................................................................................................................................................. 100
Lesh-Nyhan syndroom.................................................................................................................................................................. 100
Von Gierke.................................................................................................................................................................................... 100
Adenosine deaminase deficiëntie ................................................................................................................................................ 100
Orootzuur acidurie ....................................................................................................................................................................... 100

Extracellulaire matrix .....................................................................................................102



5

, Algemeen ................................................................................................................................................ 102
Collageen ................................................................................................................................................. 102
Ellastine en fibrilline ................................................................................................................................ 103
Glycosaminoglycanen, proteoglycanen en mucopolysachariden ............................................................. 103

Spiermetabolisme ..........................................................................................................104
Cardiac output ......................................................................................................................................... 104
Soorten spierweefsel ............................................................................................................................... 104
Spiercel .................................................................................................................................................... 104
Myofibril .................................................................................................................................................. 104
Belangrijke eiwitten................................................................................................................................. 105
Actine ........................................................................................................................................................................... 105
Myosine ....................................................................................................................................................................... 105

Spiercontractie ........................................................................................................................................ 105
Aandoeningen ......................................................................................................................................... 105
Maligne hyperthermie ................................................................................................................................................. 105
Duchenne musculaire dystrofie ................................................................................................................................... 106
Skeletspier vs hartspier ........................................................................................................................... 106
Energie .................................................................................................................................................... 106
ATP nodig voor contractie: waar komt het vandaan? .................................................................................................. 106
E-voorziening afhankelijk van soort spierweefsel ........................................................................................................ 107
E-voorziening in de tijd ................................................................................................................................................ 107

Neonatale screening ......................................................................................................108
Algemeen ................................................................................................................................................ 108
12 aandoeningen in de screening ............................................................................................................ 108
Fenylketonurie (PKU) ................................................................................................................................................... 108
Congenitale hypothyreoïdie (CHT) ............................................................................................................................... 109
Congenitale bijnierschorshyperplasie (CAH) ................................................................................................................ 109
Mean chain acyl CoA dehydrogenase deficiëntie (MCAD) ........................................................................................... 109
Multiple acyl CoA dehydrogenase deficiëntie (MADD) = glutaaracidurie type 2 (GA2) ............................................... 110
Isovaleriaanacidemie (IVA) .......................................................................................................................................... 110
Methylmalonacidemie (MMA) en Propionacidemie (PA) ............................................................................................ 110
Maple syrup urine disease (MSUD) ............................................................................................................................. 110
Glutaaracidemie type 1 (GA1) ..................................................................................................................................... 111
Biotinidase deficiëntie ................................................................................................................................................. 111
Mucoviscidose ............................................................................................................................................................. 111




6

,7

,Inleidende hoofdstukken
Bio-energetica
Rol van ATP
Bio-energetica: studie waarbij je kijkt naar de chemische energie die gepaard gaat bij het
uitvoeren van een bepaalde reactie.

Endergone en exergone reacties
E geïnvesteerd of gewonnen bij reactie:
Endergone (anabole-opbouw) Exergone (katabole-afbraak)
Energie in-/output Energie-input nodig Energie komt vrij
Spontane reactie? Reactie niet spontaan Reactie spontaan
Gunstigheid Energieongunstig Energiegunstig




Meest voorkomende reacties → endergone


Vrije energie
= Gips vrije E = energie die vrijkomt of geïnvesteerd wordt in een reactie.
→ bepaalt of de reactie al dan niet spontaan zal verlopen
• Reacties die E nodig hebben verlopen niet spontaan, maar zijn nog altijd
levensnoodzakelijk → opl.: endergone reactie zal dus gekoppeld worden aan
exergone reactie → na de 2 reacties marge E blijft over → verzekert ons dat de
reactie door zal gaan + houdt lichaamsT op peil → overmaat E zal lichaam verlaten
als warmte

Koppeling endergone en exergone reacties
Gemeenschappelijk intermediair:
• Eerste reactie brengt intermediair tot stand = substraat voor 2de reactie → verzekert
dat de reacties simultaan zullen verlopen (voordelen: zie ‘fysisch gekoppeld’)
o reactiespecifiek
• Grafiek (hierboven):
o A → B: exergone: E-rijke e- komen vrij
o C → D: endergone: E-rijke e- worden gebruikt
• Gebruik van carriers (bij dehydrogenatie): Dehydrogenatiereactie
o = eiwitten die E-rijke e- oppikken om ze later op een andere plek af te geven
waar nodig → E-winst is in evenwicht met E-verbruik (evenveel E-rijke e-
opgenomen als afgegeven)
o Niet reactiespecifiek → voordeel: verschillende metabole pathways op elkaar
afstemmen (bv: koolhydraten- en lipidenmetabolisme)


8

, Hoogenergetische componenten:
• Deze worden op een bepaalde manier en plaats
afgebroken (bv hydrolyse ATP)
• Zeer exergonisch, want de gips vrije E = negatief
• Grafiek:
o A → B: E komt vrij waardoor de
hoogenergetische component gevormd kan
worden.
o C → D: fosfaatgroep komt vrij van ATP (exergone reactie), vrijgekomen E
wordt verbruikt. De reacties worden gekoppeld door de hoogenergetische
component af te breken en aan te maken.
• Bv: de fosforylatie van glucose heeft E nodig, gaat dus niet vanzelf → opl.: reactie
samen laten verlopen met de hydrolyse van ATP
o In ATP zit adenine
• Grote voordeel: het intermediair moet niet structureel verwant zijn
• Hoogenergetische energiedrager is meestal ATP

Fysisch gekoppeld
• Voordeel: E-winst en het E-verbruik zijn evenredig aan elkaar en er wordt geen E
verbruikt die er eigenlijk niet is
o Zowel bij degene waarbij een carrier gebruikt wordt om e- te dragen als bij
degene waarbij ATP gebruikt wordt
• Bv: Fosforylatie glucose wordt gekatalyseerd door glucokinase/hexokinase (welk vd 2
de reactie katalyseert is afhankelijk van in welk deel vh lichaam we kijken). Zowel
glucose als ATP zullen zich op de actieve site vh enzyme bevinden tijdens de reactie.
o Fosforylering glucose omvat vorming van glucose-6-fosfaat + hydrolyse ATP
o Reacties gekoppeld via een intermediair, MAAR moeten ook fysisch in elkaars
buurt zijn
o Plaats waar alles zal samenkomen is bij het enzymen. Daar zal de transfer van
ATP of e- zo efficiënt mogelijk verlopen.
ATP
Algemeen
= de energy currency
• ATP maken we zelf aan in ons lichaam, MAAR brandstof nodig uit voeding.
Belangrijkste bouwstenen zijn koolhydraten, eiwitten en vetten
• Bij vorming ATP → bepaalde mate chemical waste (CO2)
• E die we in ATP steken → gebruikt om heel het metabolisme vooruit te drijven
• Overmaat E → gebruikt om lichaamsT op peil te houden (E komt vrij als warmte)
• Opbouw: adenine, ribose (vormt samen met adenine het
nucleotide adenosine) en 3 fosfaatgroepen
• E-inhoud ATP wordt enkel bepaald door
fosfaatbindingen. De E inhoud daalt wanneer men van
ATP → ADP → AMP gaat.
• In alle reacties waar ATP gebruikt wordt, zal ook altijd
magnesium betrokken zijn.




9

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