BIOCHEMIE
Inhoudsopgave
1 The scope of Biochemistry ........................................................................................... 5
1.1 Wat is biochemie ............................................................................................................ 5
1.2 Biochemie als chemische wetenschap ............................................................................. 7
1.2.1 basis bouwstenen ............................................................................................................................ 9
1.2.2 belang van stereochemie .............................................................................................................. 11
1.3 Biochemie als biologische wetenschap .......................................................................... 12
1.3.1 memranen laten cellulaire organisa8e toe .................................................................................... 13
1.3.2 biologische schaal .......................................................................................................................... 15
1.3.3 lichtmicroscopie vs electronen microscopie.................................................................................. 15
1.3.4 oppervlakte volume verhouding ................................................................................................... 16
1.3.5 specifieke cellen ............................................................................................................................ 16
2 The matrix of life: weak interac;ons in an aqueous environment .............................. 18
2.1 Soort niet-covalente interac=es..................................................................................... 18
2.1.1 vb proteïnen .................................................................................................................................. 18
2.1.2 vb nucleïnezuren ........................................................................................................................... 19
2.1.3 vb lipiden ....................................................................................................................................... 19
2.1.4 sterkte v covalente & niet-covalente interac8es ........................................................................... 20
2.1.5 electrosta8sche interac8e (tss geladen deeltjes) .......................................................................... 20
2.1.6 par8eel posi8eve of nega8eve lading............................................................................................ 21
2.1.7 Vander waals interac8es (tss niet-geladen deeltjes) ..................................................................... 21
2.1.8 waterstoLruggen .......................................................................................................................... 21
2.2 Rol water in biologische processen................................................................................ 22
2.3 Ionaire evenwichten ..................................................................................................... 25
2.3.1 Bronsted-lowry .............................................................................................................................. 25
2.3.2 henderson-hasselbach................................................................................................................... 26
2.3.3 buffers ........................................................................................................................................... 26
2.3.4 amfolieten ..................................................................................................................................... 27
2.4 Interac=es tss macro-ionen in oplossing ........................................................................ 27
2.5 Osmose......................................................................................................................... 29
2.5.1 osmose en Donnan evenwicht ...................................................................................................... 31
3 Nucleic acids: DNA and RNA...................................................................................... 33
3.1 Structuur van nucleïnezuren ......................................................................................... 33
3.1.1 basen ............................................................................................................................................. 34
3.1.2 nucleoside = suiker + base ............................................................................................................. 34
3.1.3 nucleotide = nucleoside + 5’ fosfaat groep.................................................................................... 35
3.1.4 polynucleo8de = opeenvolging van nucleo8den ........................................................................... 36
3.2 Replica=e van DNA ....................................................................................................... 43
3.3 Transcrip=e DNA " RNA ............................................................................................... 46
3.3.1 Termina8e...................................................................................................................................... 47
3.3.2 post-transcrip8onele wijzigingen .................................................................................................. 49
3.4 CTransla=e RNA " EW (prot) ........................................................................................ 49
3.4.1 post-transla8onele wijzigingen ...................................................................................................... 52
3.4.2 transcrip8e- transla8e overzicht.................................................................................................... 53
1
, 3.5 Farmaceu=sche toepassing: gentherapie ....................................................................... 54
3.5.1 plasmide DNA ................................................................................................................................ 55
3.5.2 mrna .............................................................................................................................................. 56
3.5.3 gene delivery ................................................................................................................................. 57
3.5.4 Zolgensma ® voor zeldzame spierziekte sma (baby pia)................................................................ 58
3.5.5 Luxturna® voor zeldzame oogziekte LCA ....................................................................................... 58
3.5.6 mRNA COVID-19 vaccins ................................................................................................................ 58
4 Chapter 4: introduc;e tot proteïnen: Primaire poreïne structuur ............................... 60
4.1 Structuur van a- aminozuren ........................................................................................ 60
4.1.1 stereochemie van a-aminozuren .................................................................................................. 62
4.2 Eigenschappen van de aminozuur zijketens ................................................................... 64
4.2.1 alifa8sche AZ zijketens................................................................................................................... 65
4.2.2 -OH of s beva`ende AZ zijketens ................................................................................................... 65
4.2.3 aroma8sche az zijketens ................................................................................................................ 66
4.2.4 basische az zijketens ...................................................................................................................... 67
4.2.5 zure az zijketens en hun amides .................................................................................................... 68
4.2.6 iso-elektrisch punt ......................................................................................................................... 70
4.2.7 AZ zijketens: samenvabng ............................................................................................................ 70
4.3 Pep=den en pep=de binding ......................................................................................... 71
4.3.1 polyamfoly8sch gedrag van een tetrapep8de ............................................................................... 72
4.3.2 iso-electrisch focusing ................................................................................................................... 73
4.3.3 pep8den en de pep8de binding .................................................................................................... 73
4.4 Proteïnen: polypep=den met bepaalde sequen=e ......................................................... 75
5 Drie-dimensionale structuur van proteïnen ............................................................... 76
5.1 Secundaire structuur: opvouwing polypep=de keten..................................................... 77
5.1.1 a-helix ........................................................................................................................................... 80
5.1.2 b- blad ........................................................................................................................................... 81
5.1.3 Ramachandran plot (hoeken) ........................................................................................................ 82
5.2 Fibreuze proteïnen: structureel materiaal van cellen ..................................................... 85
5.2.1 kera8nes ........................................................................................................................................ 86
5.2.2 collageen ....................................................................................................................................... 86
5.2.3 elas8ne .......................................................................................................................................... 88
5.3 Globulaire proteïnen: ter=aire structuur & func=onele diversiteit ................................. 89
5.4 Quaternaire structuur van proteïnen............................................................................. 90
6 Hemoglobine ............................................................................................................ 91
6.1 Zuurstof transport: rol van Hemoglobine en Myoglobine .............................................. 91
6.2 Mechanismen van zuursto`inding door heemproteïnen .............................................. 93
6.2.1 structuur protoporfyrine IX en heem ............................................................................................ 93
6.2.2 geometrie van ijzer coordina8e in oxymyoglobine........................................................................ 93
6.2.3 verandering in het visuele spectrum van Hb ................................................................................. 95
6.2.4 bepaling 𝜃 van myoglobine ........................................................................................................... 96
6.2.5 zuurstoLinding curve voor myoglobine ........................................................................................ 97
6.3 Zuurstoaransport: Hemoglobine ................................................................................... 98
6.3.1 coöpera8eve vs niet-coöpera8eve O2-binding curves .................................................................. 99
6.3.2 hill plot......................................................................................................................................... 100
6.3.3 twee modellen voor de coöpera8eve ligand binding door Hb .................................................... 102
6.4 “Perutz mechanisme” ................................................................................................. 106
2
, 6.5 Allosterische effectors van Hemoglobine ..................................................................... 107
6.5.1 pH: bohr effect............................................................................................................................. 108
6.5.2 CO2 ............................................................................................................................................... 109
6.5.3 2,3-biphosphoglyceraat (2,3-BPG) ............................................................................................... 110
7 Enzymen: biologische katalysatoren ....................................................................... 114
7.1 De rol van enzymen .................................................................................................... 114
7.1.1 enzymen = biologische katalysatoren .......................................................................................... 114
7.1.2 enzyme klassen obv func8e......................................................................................................... 115
7.2 Cofactoren, vitaminen & essen=ële metalen ............................................................... 117
7.2.1 cofactoren ................................................................................................................................... 117
7.2.2 vitaminen..................................................................................................................................... 117
7.2.3 (metaal)ionen .............................................................................................................................. 119
7.3 Benodigde energie en rich=ng van een reac=e ............................................................ 119
7.3.1 de biochemische standaard toestand.......................................................................................... 123
7.4 Chemische reac=e snelheid en het effect van katalyse ................................................ 124
7.4.1 reac8esnelheid ............................................................................................................................ 124
7.4.2 binding substraat-enzym ............................................................................................................. 124
7.4.3 ac8va8e-energie .......................................................................................................................... 125
7.5 Hoe treden enzymes op als katalysatoren: principes & voorbeelden ........................... 129
7.5.1 twee modellen vr enzyme-substraat interac8e ........................................................................... 130
7.5.2 samenvabng enzyme .................................................................................................................. 130
7.6 Kine=ek van enzyma=sche katalyse: Michaelis Menten............................................... 131
7.6.1 steady state in enzyme kine8cs ................................................................................................... 133
7.7 Enzyme efficiën=e ....................................................................................................... 137
7.8 Reac=es met 2 of meerdere substraten ....................................................................... 138
7.8.1 willekeurige sequen8ële substraatbinding .................................................................................. 138
7.8.2 geordende sequen8ële substraatbinding .................................................................................... 138
7.8.3 ping-pong mechanisme ............................................................................................................... 139
7.9 Enzym inhibi=e ........................................................................................................... 140
7.9.1 reversibele inhibi8e ..................................................................................................................... 140
7.9.2 irreversibele inhibi8e ................................................................................................................... 149
7.10 Regula=e van enzyme ac=viteit ................................................................................... 150
7.10.1 allosterische enzymen ............................................................................................................ 150
7.10.2 covalente modifica8es om enzyme ac8viteit te regelen ........................................................ 153
8 Koolhydraten: suikers, sacchariden, glycanen ......................................................... 154
8.1 Monosacchariden ....................................................................................................... 156
8.1.1 triosen (n=3) ................................................................................................................................ 156
8.1.2 tetrosen (n = 4) ............................................................................................................................ 158
8.1.3 pentosen (n = 5) .......................................................................................................................... 159
8.1.4 hexosen (n = 6) ............................................................................................................................ 160
8.1.5 ringstructuren van monosacchariden.......................................................................................... 162
8.1.6 derivaten van monosacchariden ................................................................................................. 168
8.2 Disacchariden ............................................................................................................. 173
8.2.1 stabiliteit van glycosidische binding ............................................................................................ 176
8.3 Polysacchariden .......................................................................................................... 178
8.3.1 opslag-polysacchariden ............................................................................................................... 178
8.3.2 structurele polysacchariden in plant ........................................................................................... 181
8.3.3 structurele polysacchariden in mens & dier ................................................................................ 182
3
, 8.4 Koolhydraten als informa=e molecule: ‘the sugar code’ .............................................. 185
8.4.1 oligosaccharides als cel merkers.................................................................................................. 185
8.4.2 glycoproteïnen ............................................................................................................................. 185
8.4.3 glycolipide.................................................................................................................................... 186
9 Lipiden .................................................................................................................... 188
9.1 Moleculaire structuur & gedrag van lipiden................................................................. 188
9.1.1 vetzuren ....................................................................................................................................... 189
9.1.2 triglyceriden (triaglycerolen of ve`en) ........................................................................................ 191
9.1.3 zepen & detergenten ................................................................................................................... 192
9.1.4 wassen ......................................................................................................................................... 193
9.2 Lipide cons=tuenten van biologische membranen ....................................................... 194
9.2.1 glycerofosfolipiden (= fosfolipiden) ............................................................................................ 195
9.2.2 sfingolipiden & glycosfingolipiden ............................................................................................... 196
9.2.3 cholesterol ................................................................................................................................... 198
9.3 Structuur & eigenschappen v membranen & mebraanproteïnen ................................. 199
9.3.1 beweging in membranen ............................................................................................................. 200
9.4 Transport doorheen membranen ................................................................................ 202
9.4.1 passieve diffusie .......................................................................................................................... 202
9.4.2 gefaciliteerde diffusie .................................................................................................................. 203
9.4.3 ac8ef transport ............................................................................................................................ 204
9.5 Energe=sche aspecten van transport over membranen ............................................... 207
9.5.1 passieve diffusie .......................................................................................................................... 207
9.5.2 ionair & ac8ef transport .............................................................................................................. 208
9.5.3 cotransport .................................................................................................................................. 210
9.5.4 transport door modifica8e .......................................................................................................... 211
9.5.5 manieren om obesitas te bestrijden............................................................................................ 211
9.6 Eicosanoïden & NSAIDs ............................................................................................... 212
9.6.1 eicosanoïden: prostaglandines, thromboxanen & leukotriënen ................................................. 212
9.6.2 aanmaak/ synthese eicosanoïden ............................................................................................... 212
9.6.3 close-up eicosanoïden synthese .................................................................................................. 214
9.6.4 COX inhibitoren ........................................................................................................................... 214
9.7 Cholesterol synthese & sta=nes .................................................................................. 218
9.7.1 cholesterol structuur ................................................................................................................... 218
9.7.2 aanmaak cholesterol, via mevalonaat & IPP ............................................................................... 218
9.7.3 regula8e van HMG-CoA reductase .............................................................................................. 220
4
,1 The scope of Biochemistry
¨ Chapter outline:
• Wat is biochemie?
• Biochemie als chemische wetenschap
• Biochemie als biologische wetenschap
1.1 Wat is biochemie
¨ Biochemie = bestuderen van levende organismen op moleculair niveau
¨ Onderscheiding levende materie <-> niet levende materie
• Grens w steeds nauwer/moeilijker (bij meer geavanceerde zaken)
§ Vb virus = dunne lijn (gastheer nodig)
¨ 3 hoofddisciplines
1. Structurele chemie vd componenten v levende materie & relaNe tss biologische
funcNe & chemische structuur
Ø Hoe reageert molecule obv structuur?
2. Metabolisme
Ø Totaal v (mogelijke) chemische reacNes die in levende materie (lichaam) optreden
Ø Vb. aRreken voedsel " E
3. GeneNsche biochemie
Ø Chemie v processen & substanNes die biologische info bewaren & overdragen
Ø Omvat ook moleculaire geneNca " onderzoekt erfelijkheid & expressie
geneNsche info in moleculaire termen
Ø DNA, RNA, hoe w info in lichaam gecontroleerd zodat processen kunnen
doorgaan
¨ Geschiedenis
• IniNeel gedacht: chemische & fysische processen in levende materie totaal
verschillend dan processen in niet-levende materie
• Maar:
• 1828: Friedrich Wöhler " ureum kan gesyntheNseerd w zonder nood aan
nier/ levend wezen " ureum: wortel v biochemie => eerste synthese v
biologische molecule van niet-biologische precursoren
• 1897: Eduard & Hans Buchner " fermentaNe suiker tot ethanol kan w
uitgevoerd met extracten v gist, ook al zijn gist-cellen na extracNe niet meer
levend (levend of niet " componenten zorgen vr reacNes)
Ø Mogelijke reacNes in vitro & in vivo zijn essenNeel dezelfde (reacNes op
zich niet verschillend, gwn manier waarop)
Ø Uniek karakter v organisme = enkel bepaald door totaliteit v chemische
reacNes, niet door aard v reacNe op zich
" enzymen = “ferments” (<1926)
" abio:sch = zonder betrokkenheid v levend systeem
" oorspr: men dacht dat nucleïnezuren structurele rol hadden
5
,¨ Koshland’s 7 “pillars of life”
ð Bepalen hoe we erin slagen om onze chemische reacNes op goeie manier
georganiseerd te krijgen
1. Programma
Ø Georganiseerd plan vr opbouw & regeneraNe v organisme (DNA)
2. ImprovisaNe
Ø Mogelijkheid v levend organisme om het programma aan te passen om
overleving te verzekeren in veranderde omgeving
Ø = aanpassing op lange termijn
Ø Vb DNA mutaNes
Ø (natuurlijke selecNe)
3. ComparNmentalisaNe
Ø Mogelijkheid v levend organisme om zichzelf v omgeving af te scheiden, vb met
membranen (cellen, celorganellen,..)
Ø Chemische reacNes afscheiden dmv comparNmenten (geen interferenNe)
Ø Lipidenmembranen
4. Energie
Ø Levende materie bevat complex geheel v (chemische & kineNsche) processen
om programma & andere “pillars of life” te onderhouden " vereist energie
5. RegeneraNe
Ø Mogelijkheid om te compenseren vr “slijtage” (vb synthese nieuwe proteïnen v
oudere, versleten proteïnen)
Ø Kapome/versleten onderdelen vervangen
Ø Niet alles kan vervangen w (vb fotoreceptoren)
6. Aanpassingsvermogen
Ø Vermogen om te reageren op omgevingsfactoren
Ø = aanpassing op korte termijn
Ø Vb honger " eten
Ø Vb pijnprikkel " hand wegtrekken
7. Afscheiding
Ø Metabole processen & pathways kunnen in isolaNe v elkaar doorgaan, zelfs
indien ze in zelfde celcomparNment (vb cytoplasma) plaatsvinden (enzyme
specificiteit)
Ø Vb in zelfde comparNment zowel omzeong glucose " pyridine als omzeong
pyridine " glucose
• Enzymen bepalen welke richNng/ reacNe doorgaat (ap v wat lichaam
nodig heeq)
6
,¨ Belangrijke principes om “pillars of life” te onderhouden:
• Semipermeabele membranen
§ Omgeven cellen & intracellulaire celorganellen (vb mitochondria)
§ = alle membranen in lichaam
§ SelecNef doorlaatbaar vr bepaalde moleculen, andere w
tegengehouden
• Homeostase
§ Fysische & chemische composiNe v biologisch syst w constant gehouden
binnen bepaalde range
§ Oa dmv semipermeabele membranen
§ Vb temp, pH, ionenceonc,…
§ ≠ chemisch evenwicht !!!
Ø Homeostase: alle reacNes zo op elkaar afgestemd zodat stabiele staat
Ø Vaste verhoudingen (componenten tov elkaar) (E nodig om
verhoudingen te verkrijgen)
§ <-> evenwicht: geen energie nodig
§ Homeostase binnen bepaalde range verstoord " lichaam kan
ingrijpen/herstellen
§ // te veel verstoord " lichaam kan niet meer herstellen (vb visolie Sanda Dia "
ionenbalans verstoord)
" non-equilibrium steady state
1.2 Biochemie als chemische wetenschap
¨ Elementen in organismen:
• Eerste rij (meest aanwezig)
§ 4 basiselementen: C, H, O, N
§ > 99% v celmassa
§ 50% v droge cel = uit C
• Tweede rij (minder, maar wel belangrijk)
§ S, P, Na+ , K+,Cl- Ca2+, Mg2+
• Derde rij
§ Fe " in Hg (O2 transport)
• Vierde rij
§ Spoorelementen (in bepaalde organismen)
¨ Veelzijdigheid C-verbinding:
• C kan 4 verb aangaan
• H: 1 verb
• N: 3 verb
• O: 2 verb
7
,¨ Belangrijke chemische verbindingen:
Methyl Ethyl
Phenyl Amino
Amido Carbonyl (aldehyde)
Carbonyl (keton) Carboxyl
Hydroxyl (alcohol) Ether
Ester Phosphoryl
Sulpydryl Disulfide
" disulfidebrug (verb maken tss versch delen v EW
" vastklikken " 3D struct)
Thioester
8
, " acetyl CoA
" versch groepen kunnen
herkennen in molecules !
1.2.1 BASIS BOUWSTENEN
Macromolculen (uit micro) Micromoleculen Linker
(meeste = polymeer) (= bouwstenen om EW te (om bouwstenen te
vormen) koppelen)
Proteïnen AZ’en PepNde (amide)
Polysacchariden Monosacchariden Glycoside (ether)
(vb cellulose) (glucose)
Nucleïnezuren NucleoNden Fosfodiëster
(lipiden) (max 3 VZ’en om (vetzuren) ester
lipide te vormen " niet echt
polymeer)
" cellulose = homopolymeer " uit idenNeke monomeren
" veel polysacchariden, alle nucleïnezuren, alle proteïnen = heteropolymeren " uit versch
soorten monomeren
" zetmeel = glucose polymeer (planten) (homopolymeer)
¨ Vb polysaccharide
9
, ¨ Vb polynucleoNde
• DNA: A,C,G,T
• RNA: A,C,G,U
¨ Vb polypepNde
¨ Chemische reacNes VS biochemische reacNes: essenNeel zelfde, maar:
10
Inhoudsopgave
1 The scope of Biochemistry ........................................................................................... 5
1.1 Wat is biochemie ............................................................................................................ 5
1.2 Biochemie als chemische wetenschap ............................................................................. 7
1.2.1 basis bouwstenen ............................................................................................................................ 9
1.2.2 belang van stereochemie .............................................................................................................. 11
1.3 Biochemie als biologische wetenschap .......................................................................... 12
1.3.1 memranen laten cellulaire organisa8e toe .................................................................................... 13
1.3.2 biologische schaal .......................................................................................................................... 15
1.3.3 lichtmicroscopie vs electronen microscopie.................................................................................. 15
1.3.4 oppervlakte volume verhouding ................................................................................................... 16
1.3.5 specifieke cellen ............................................................................................................................ 16
2 The matrix of life: weak interac;ons in an aqueous environment .............................. 18
2.1 Soort niet-covalente interac=es..................................................................................... 18
2.1.1 vb proteïnen .................................................................................................................................. 18
2.1.2 vb nucleïnezuren ........................................................................................................................... 19
2.1.3 vb lipiden ....................................................................................................................................... 19
2.1.4 sterkte v covalente & niet-covalente interac8es ........................................................................... 20
2.1.5 electrosta8sche interac8e (tss geladen deeltjes) .......................................................................... 20
2.1.6 par8eel posi8eve of nega8eve lading............................................................................................ 21
2.1.7 Vander waals interac8es (tss niet-geladen deeltjes) ..................................................................... 21
2.1.8 waterstoLruggen .......................................................................................................................... 21
2.2 Rol water in biologische processen................................................................................ 22
2.3 Ionaire evenwichten ..................................................................................................... 25
2.3.1 Bronsted-lowry .............................................................................................................................. 25
2.3.2 henderson-hasselbach................................................................................................................... 26
2.3.3 buffers ........................................................................................................................................... 26
2.3.4 amfolieten ..................................................................................................................................... 27
2.4 Interac=es tss macro-ionen in oplossing ........................................................................ 27
2.5 Osmose......................................................................................................................... 29
2.5.1 osmose en Donnan evenwicht ...................................................................................................... 31
3 Nucleic acids: DNA and RNA...................................................................................... 33
3.1 Structuur van nucleïnezuren ......................................................................................... 33
3.1.1 basen ............................................................................................................................................. 34
3.1.2 nucleoside = suiker + base ............................................................................................................. 34
3.1.3 nucleotide = nucleoside + 5’ fosfaat groep.................................................................................... 35
3.1.4 polynucleo8de = opeenvolging van nucleo8den ........................................................................... 36
3.2 Replica=e van DNA ....................................................................................................... 43
3.3 Transcrip=e DNA " RNA ............................................................................................... 46
3.3.1 Termina8e...................................................................................................................................... 47
3.3.2 post-transcrip8onele wijzigingen .................................................................................................. 49
3.4 CTransla=e RNA " EW (prot) ........................................................................................ 49
3.4.1 post-transla8onele wijzigingen ...................................................................................................... 52
3.4.2 transcrip8e- transla8e overzicht.................................................................................................... 53
1
, 3.5 Farmaceu=sche toepassing: gentherapie ....................................................................... 54
3.5.1 plasmide DNA ................................................................................................................................ 55
3.5.2 mrna .............................................................................................................................................. 56
3.5.3 gene delivery ................................................................................................................................. 57
3.5.4 Zolgensma ® voor zeldzame spierziekte sma (baby pia)................................................................ 58
3.5.5 Luxturna® voor zeldzame oogziekte LCA ....................................................................................... 58
3.5.6 mRNA COVID-19 vaccins ................................................................................................................ 58
4 Chapter 4: introduc;e tot proteïnen: Primaire poreïne structuur ............................... 60
4.1 Structuur van a- aminozuren ........................................................................................ 60
4.1.1 stereochemie van a-aminozuren .................................................................................................. 62
4.2 Eigenschappen van de aminozuur zijketens ................................................................... 64
4.2.1 alifa8sche AZ zijketens................................................................................................................... 65
4.2.2 -OH of s beva`ende AZ zijketens ................................................................................................... 65
4.2.3 aroma8sche az zijketens ................................................................................................................ 66
4.2.4 basische az zijketens ...................................................................................................................... 67
4.2.5 zure az zijketens en hun amides .................................................................................................... 68
4.2.6 iso-elektrisch punt ......................................................................................................................... 70
4.2.7 AZ zijketens: samenvabng ............................................................................................................ 70
4.3 Pep=den en pep=de binding ......................................................................................... 71
4.3.1 polyamfoly8sch gedrag van een tetrapep8de ............................................................................... 72
4.3.2 iso-electrisch focusing ................................................................................................................... 73
4.3.3 pep8den en de pep8de binding .................................................................................................... 73
4.4 Proteïnen: polypep=den met bepaalde sequen=e ......................................................... 75
5 Drie-dimensionale structuur van proteïnen ............................................................... 76
5.1 Secundaire structuur: opvouwing polypep=de keten..................................................... 77
5.1.1 a-helix ........................................................................................................................................... 80
5.1.2 b- blad ........................................................................................................................................... 81
5.1.3 Ramachandran plot (hoeken) ........................................................................................................ 82
5.2 Fibreuze proteïnen: structureel materiaal van cellen ..................................................... 85
5.2.1 kera8nes ........................................................................................................................................ 86
5.2.2 collageen ....................................................................................................................................... 86
5.2.3 elas8ne .......................................................................................................................................... 88
5.3 Globulaire proteïnen: ter=aire structuur & func=onele diversiteit ................................. 89
5.4 Quaternaire structuur van proteïnen............................................................................. 90
6 Hemoglobine ............................................................................................................ 91
6.1 Zuurstof transport: rol van Hemoglobine en Myoglobine .............................................. 91
6.2 Mechanismen van zuursto`inding door heemproteïnen .............................................. 93
6.2.1 structuur protoporfyrine IX en heem ............................................................................................ 93
6.2.2 geometrie van ijzer coordina8e in oxymyoglobine........................................................................ 93
6.2.3 verandering in het visuele spectrum van Hb ................................................................................. 95
6.2.4 bepaling 𝜃 van myoglobine ........................................................................................................... 96
6.2.5 zuurstoLinding curve voor myoglobine ........................................................................................ 97
6.3 Zuurstoaransport: Hemoglobine ................................................................................... 98
6.3.1 coöpera8eve vs niet-coöpera8eve O2-binding curves .................................................................. 99
6.3.2 hill plot......................................................................................................................................... 100
6.3.3 twee modellen voor de coöpera8eve ligand binding door Hb .................................................... 102
6.4 “Perutz mechanisme” ................................................................................................. 106
2
, 6.5 Allosterische effectors van Hemoglobine ..................................................................... 107
6.5.1 pH: bohr effect............................................................................................................................. 108
6.5.2 CO2 ............................................................................................................................................... 109
6.5.3 2,3-biphosphoglyceraat (2,3-BPG) ............................................................................................... 110
7 Enzymen: biologische katalysatoren ....................................................................... 114
7.1 De rol van enzymen .................................................................................................... 114
7.1.1 enzymen = biologische katalysatoren .......................................................................................... 114
7.1.2 enzyme klassen obv func8e......................................................................................................... 115
7.2 Cofactoren, vitaminen & essen=ële metalen ............................................................... 117
7.2.1 cofactoren ................................................................................................................................... 117
7.2.2 vitaminen..................................................................................................................................... 117
7.2.3 (metaal)ionen .............................................................................................................................. 119
7.3 Benodigde energie en rich=ng van een reac=e ............................................................ 119
7.3.1 de biochemische standaard toestand.......................................................................................... 123
7.4 Chemische reac=e snelheid en het effect van katalyse ................................................ 124
7.4.1 reac8esnelheid ............................................................................................................................ 124
7.4.2 binding substraat-enzym ............................................................................................................. 124
7.4.3 ac8va8e-energie .......................................................................................................................... 125
7.5 Hoe treden enzymes op als katalysatoren: principes & voorbeelden ........................... 129
7.5.1 twee modellen vr enzyme-substraat interac8e ........................................................................... 130
7.5.2 samenvabng enzyme .................................................................................................................. 130
7.6 Kine=ek van enzyma=sche katalyse: Michaelis Menten............................................... 131
7.6.1 steady state in enzyme kine8cs ................................................................................................... 133
7.7 Enzyme efficiën=e ....................................................................................................... 137
7.8 Reac=es met 2 of meerdere substraten ....................................................................... 138
7.8.1 willekeurige sequen8ële substraatbinding .................................................................................. 138
7.8.2 geordende sequen8ële substraatbinding .................................................................................... 138
7.8.3 ping-pong mechanisme ............................................................................................................... 139
7.9 Enzym inhibi=e ........................................................................................................... 140
7.9.1 reversibele inhibi8e ..................................................................................................................... 140
7.9.2 irreversibele inhibi8e ................................................................................................................... 149
7.10 Regula=e van enzyme ac=viteit ................................................................................... 150
7.10.1 allosterische enzymen ............................................................................................................ 150
7.10.2 covalente modifica8es om enzyme ac8viteit te regelen ........................................................ 153
8 Koolhydraten: suikers, sacchariden, glycanen ......................................................... 154
8.1 Monosacchariden ....................................................................................................... 156
8.1.1 triosen (n=3) ................................................................................................................................ 156
8.1.2 tetrosen (n = 4) ............................................................................................................................ 158
8.1.3 pentosen (n = 5) .......................................................................................................................... 159
8.1.4 hexosen (n = 6) ............................................................................................................................ 160
8.1.5 ringstructuren van monosacchariden.......................................................................................... 162
8.1.6 derivaten van monosacchariden ................................................................................................. 168
8.2 Disacchariden ............................................................................................................. 173
8.2.1 stabiliteit van glycosidische binding ............................................................................................ 176
8.3 Polysacchariden .......................................................................................................... 178
8.3.1 opslag-polysacchariden ............................................................................................................... 178
8.3.2 structurele polysacchariden in plant ........................................................................................... 181
8.3.3 structurele polysacchariden in mens & dier ................................................................................ 182
3
, 8.4 Koolhydraten als informa=e molecule: ‘the sugar code’ .............................................. 185
8.4.1 oligosaccharides als cel merkers.................................................................................................. 185
8.4.2 glycoproteïnen ............................................................................................................................. 185
8.4.3 glycolipide.................................................................................................................................... 186
9 Lipiden .................................................................................................................... 188
9.1 Moleculaire structuur & gedrag van lipiden................................................................. 188
9.1.1 vetzuren ....................................................................................................................................... 189
9.1.2 triglyceriden (triaglycerolen of ve`en) ........................................................................................ 191
9.1.3 zepen & detergenten ................................................................................................................... 192
9.1.4 wassen ......................................................................................................................................... 193
9.2 Lipide cons=tuenten van biologische membranen ....................................................... 194
9.2.1 glycerofosfolipiden (= fosfolipiden) ............................................................................................ 195
9.2.2 sfingolipiden & glycosfingolipiden ............................................................................................... 196
9.2.3 cholesterol ................................................................................................................................... 198
9.3 Structuur & eigenschappen v membranen & mebraanproteïnen ................................. 199
9.3.1 beweging in membranen ............................................................................................................. 200
9.4 Transport doorheen membranen ................................................................................ 202
9.4.1 passieve diffusie .......................................................................................................................... 202
9.4.2 gefaciliteerde diffusie .................................................................................................................. 203
9.4.3 ac8ef transport ............................................................................................................................ 204
9.5 Energe=sche aspecten van transport over membranen ............................................... 207
9.5.1 passieve diffusie .......................................................................................................................... 207
9.5.2 ionair & ac8ef transport .............................................................................................................. 208
9.5.3 cotransport .................................................................................................................................. 210
9.5.4 transport door modifica8e .......................................................................................................... 211
9.5.5 manieren om obesitas te bestrijden............................................................................................ 211
9.6 Eicosanoïden & NSAIDs ............................................................................................... 212
9.6.1 eicosanoïden: prostaglandines, thromboxanen & leukotriënen ................................................. 212
9.6.2 aanmaak/ synthese eicosanoïden ............................................................................................... 212
9.6.3 close-up eicosanoïden synthese .................................................................................................. 214
9.6.4 COX inhibitoren ........................................................................................................................... 214
9.7 Cholesterol synthese & sta=nes .................................................................................. 218
9.7.1 cholesterol structuur ................................................................................................................... 218
9.7.2 aanmaak cholesterol, via mevalonaat & IPP ............................................................................... 218
9.7.3 regula8e van HMG-CoA reductase .............................................................................................. 220
4
,1 The scope of Biochemistry
¨ Chapter outline:
• Wat is biochemie?
• Biochemie als chemische wetenschap
• Biochemie als biologische wetenschap
1.1 Wat is biochemie
¨ Biochemie = bestuderen van levende organismen op moleculair niveau
¨ Onderscheiding levende materie <-> niet levende materie
• Grens w steeds nauwer/moeilijker (bij meer geavanceerde zaken)
§ Vb virus = dunne lijn (gastheer nodig)
¨ 3 hoofddisciplines
1. Structurele chemie vd componenten v levende materie & relaNe tss biologische
funcNe & chemische structuur
Ø Hoe reageert molecule obv structuur?
2. Metabolisme
Ø Totaal v (mogelijke) chemische reacNes die in levende materie (lichaam) optreden
Ø Vb. aRreken voedsel " E
3. GeneNsche biochemie
Ø Chemie v processen & substanNes die biologische info bewaren & overdragen
Ø Omvat ook moleculaire geneNca " onderzoekt erfelijkheid & expressie
geneNsche info in moleculaire termen
Ø DNA, RNA, hoe w info in lichaam gecontroleerd zodat processen kunnen
doorgaan
¨ Geschiedenis
• IniNeel gedacht: chemische & fysische processen in levende materie totaal
verschillend dan processen in niet-levende materie
• Maar:
• 1828: Friedrich Wöhler " ureum kan gesyntheNseerd w zonder nood aan
nier/ levend wezen " ureum: wortel v biochemie => eerste synthese v
biologische molecule van niet-biologische precursoren
• 1897: Eduard & Hans Buchner " fermentaNe suiker tot ethanol kan w
uitgevoerd met extracten v gist, ook al zijn gist-cellen na extracNe niet meer
levend (levend of niet " componenten zorgen vr reacNes)
Ø Mogelijke reacNes in vitro & in vivo zijn essenNeel dezelfde (reacNes op
zich niet verschillend, gwn manier waarop)
Ø Uniek karakter v organisme = enkel bepaald door totaliteit v chemische
reacNes, niet door aard v reacNe op zich
" enzymen = “ferments” (<1926)
" abio:sch = zonder betrokkenheid v levend systeem
" oorspr: men dacht dat nucleïnezuren structurele rol hadden
5
,¨ Koshland’s 7 “pillars of life”
ð Bepalen hoe we erin slagen om onze chemische reacNes op goeie manier
georganiseerd te krijgen
1. Programma
Ø Georganiseerd plan vr opbouw & regeneraNe v organisme (DNA)
2. ImprovisaNe
Ø Mogelijkheid v levend organisme om het programma aan te passen om
overleving te verzekeren in veranderde omgeving
Ø = aanpassing op lange termijn
Ø Vb DNA mutaNes
Ø (natuurlijke selecNe)
3. ComparNmentalisaNe
Ø Mogelijkheid v levend organisme om zichzelf v omgeving af te scheiden, vb met
membranen (cellen, celorganellen,..)
Ø Chemische reacNes afscheiden dmv comparNmenten (geen interferenNe)
Ø Lipidenmembranen
4. Energie
Ø Levende materie bevat complex geheel v (chemische & kineNsche) processen
om programma & andere “pillars of life” te onderhouden " vereist energie
5. RegeneraNe
Ø Mogelijkheid om te compenseren vr “slijtage” (vb synthese nieuwe proteïnen v
oudere, versleten proteïnen)
Ø Kapome/versleten onderdelen vervangen
Ø Niet alles kan vervangen w (vb fotoreceptoren)
6. Aanpassingsvermogen
Ø Vermogen om te reageren op omgevingsfactoren
Ø = aanpassing op korte termijn
Ø Vb honger " eten
Ø Vb pijnprikkel " hand wegtrekken
7. Afscheiding
Ø Metabole processen & pathways kunnen in isolaNe v elkaar doorgaan, zelfs
indien ze in zelfde celcomparNment (vb cytoplasma) plaatsvinden (enzyme
specificiteit)
Ø Vb in zelfde comparNment zowel omzeong glucose " pyridine als omzeong
pyridine " glucose
• Enzymen bepalen welke richNng/ reacNe doorgaat (ap v wat lichaam
nodig heeq)
6
,¨ Belangrijke principes om “pillars of life” te onderhouden:
• Semipermeabele membranen
§ Omgeven cellen & intracellulaire celorganellen (vb mitochondria)
§ = alle membranen in lichaam
§ SelecNef doorlaatbaar vr bepaalde moleculen, andere w
tegengehouden
• Homeostase
§ Fysische & chemische composiNe v biologisch syst w constant gehouden
binnen bepaalde range
§ Oa dmv semipermeabele membranen
§ Vb temp, pH, ionenceonc,…
§ ≠ chemisch evenwicht !!!
Ø Homeostase: alle reacNes zo op elkaar afgestemd zodat stabiele staat
Ø Vaste verhoudingen (componenten tov elkaar) (E nodig om
verhoudingen te verkrijgen)
§ <-> evenwicht: geen energie nodig
§ Homeostase binnen bepaalde range verstoord " lichaam kan
ingrijpen/herstellen
§ // te veel verstoord " lichaam kan niet meer herstellen (vb visolie Sanda Dia "
ionenbalans verstoord)
" non-equilibrium steady state
1.2 Biochemie als chemische wetenschap
¨ Elementen in organismen:
• Eerste rij (meest aanwezig)
§ 4 basiselementen: C, H, O, N
§ > 99% v celmassa
§ 50% v droge cel = uit C
• Tweede rij (minder, maar wel belangrijk)
§ S, P, Na+ , K+,Cl- Ca2+, Mg2+
• Derde rij
§ Fe " in Hg (O2 transport)
• Vierde rij
§ Spoorelementen (in bepaalde organismen)
¨ Veelzijdigheid C-verbinding:
• C kan 4 verb aangaan
• H: 1 verb
• N: 3 verb
• O: 2 verb
7
,¨ Belangrijke chemische verbindingen:
Methyl Ethyl
Phenyl Amino
Amido Carbonyl (aldehyde)
Carbonyl (keton) Carboxyl
Hydroxyl (alcohol) Ether
Ester Phosphoryl
Sulpydryl Disulfide
" disulfidebrug (verb maken tss versch delen v EW
" vastklikken " 3D struct)
Thioester
8
, " acetyl CoA
" versch groepen kunnen
herkennen in molecules !
1.2.1 BASIS BOUWSTENEN
Macromolculen (uit micro) Micromoleculen Linker
(meeste = polymeer) (= bouwstenen om EW te (om bouwstenen te
vormen) koppelen)
Proteïnen AZ’en PepNde (amide)
Polysacchariden Monosacchariden Glycoside (ether)
(vb cellulose) (glucose)
Nucleïnezuren NucleoNden Fosfodiëster
(lipiden) (max 3 VZ’en om (vetzuren) ester
lipide te vormen " niet echt
polymeer)
" cellulose = homopolymeer " uit idenNeke monomeren
" veel polysacchariden, alle nucleïnezuren, alle proteïnen = heteropolymeren " uit versch
soorten monomeren
" zetmeel = glucose polymeer (planten) (homopolymeer)
¨ Vb polysaccharide
9
, ¨ Vb polynucleoNde
• DNA: A,C,G,T
• RNA: A,C,G,U
¨ Vb polypepNde
¨ Chemische reacNes VS biochemische reacNes: essenNeel zelfde, maar:
10
