Inhoudsopgave
1.1. Inleiding.................................................................................................................................................. 5
1.2. Metabole paden & metabole flux............................................................................................................ 6
1.2.1. Katabole wegen: 4-fasenplan vr netto energievrijstelling..........................................................................7
1.2.2. Anabole wegen: energie-vereisende processen.........................................................................................7
1.2.3. Amphibole reacties.....................................................................................................................................7
1.3. Cellulaire localisaties v metabole paden..................................................................................................8
1.4. Aangeboren metabole ziektes................................................................................................................. 8
1.4.1. Galactosemie..............................................................................................................................................8
1.4.2. Metabool syndroom/syndroom X...............................................................................................................8
2.1. Van glucose (hexose) nr pyruvaat (triose)................................................................................................ 8
Box 1: vorming v 2,3-BPG in rode bloedcellen...............................................................................................11
2.2. Het lot v pyruvaat: anaëroob metabolisme............................................................................................ 11
2.2.1. Van pyruvaat nr ethanol (gistcel).............................................................................................................11
2.2.2. Van pyruvaat nr lactaat (spiercel)............................................................................................................11
box 2: het melkzuur bij lange afstandslopers.................................................................................................12
2.3. vrije energieveranderingen vd glycolyse................................................................................................ 12
2.4. regulatie vd glycolyse............................................................................................................................ 12
2.4.1. regulatie vh hexose transport...................................................................................................................12
2.4.2. Regulatie v hexokinase.............................................................................................................................13
2.4.3. regulatie v fosfofructokinase-1 (PFK-1)....................................................................................................13
2.4.4. Regulatie v pyruvaatkinase (PK)= feedforward regulatie........................................................................13
2.5. Andere suikers die glycolyse-weg vervoegen......................................................................................... 14
Box 3: metaole stoornis Galactosemie...........................................................................................................14
box 4: lactose-intolerantie, normaal of abnormaal?.....................................................................................14
3.1. mitochondriale koolstofverbranding= tweestapsproces........................................................................15
3.2. Oxidatieve decarboxylering................................................................................................................... 15
3.2.1. Pyruvaatdehydrogenase-complex............................................................................................................15
3.2.2. Regulatie v pyruvaatdehydrogenase........................................................................................................16
3.3. citroenzuurcyclus/Krebs cyclus.............................................................................................................. 16
3.3.1. van acetyl-CoA nr CO2...............................................................................................................................16
3.3.2. Waar komen de elektronen id citroenzuurcylcus?...................................................................................18
3.3.3. Gereduceerde coenzymen kù bevoorrading v ATP verzorgen..................................................................18
4.1. elektronentransport & ATP synthese: inleiding......................................................................................19
1
, 4.2. Hoeveel energie komt vrij bij het elektronentransport?..............................................................................20
4.3. Eiwitcomplexen vd elektronentransportketen.......................................................................................20
4.3.1. Complex I..................................................................................................................................................20
4.3.2. Complex II.................................................................................................................................................21
4.3.3. Complex III................................................................................................................................................21
4.3.4. Complex IV................................................................................................................................................22
4.3.5. Complex V.................................................................................................................................................22
4.4. De respiratoire ontkoppeling................................................................................................................. 22
Inhibtoren vd elektronenstransportketen.....................................................................................................23
4.5. Het gevaar v reactieve zuurstofradicalen....................................................................................................23
Respiratoire supercomplexen........................................................................................................................24
4.6. Mitochondirale ziekten................................................................................................................................24
Box 5: superoxide dismutase (SOD) & ALS.....................................................................................................24
5.1. situering & inleiding.............................................................................................................................. 25
Diabetes/suikerziekte.....................................................................................................................................25
5.2. Glycogenolyse= afbraak v glycogeen...................................................................................................... 26
5.3. Het lot v glucose-1-fosfaat in lever & spieren......................................................................................... 27
5.4. Glycogeensynthese............................................................................................................................... 27
5.5. Regulatie v glycogeenmetabolisme........................................................................................................ 27
5.5.1. Regulatie v glycogeenfosforylase => HORMONAAL.................................................................................28
5.6. Glycogenosen........................................................................................................................................ 28
5.6.1. GSD I/ von Gierke’s ziekte.........................................................................................................................28
5.6.2. GSD II/ziekte v Pompe..............................................................................................................................29
5.6.3. GSD III/ ziekte v Cori.................................................................................................................................29
5.6.4. GDS V/ziekte v McArdle............................................................................................................................29
6.1. inleiding................................................................................................................................................ 29
6.2. Gluconeogenese-enzymen..................................................................................................................... 30
6.2.1. Pyruvaat carboxylase...............................................................................................................................30
6.2.2. Fosfoenol pyruvaat carboxykinase (PEPCK).............................................................................................30
Supermuis.......................................................................................................................................................30
6.2.3. Fructose-1,6-bifosfatase...........................................................................................................................30
6.2.4. Glucose-6-fosfatase..................................................................................................................................30
6.3. Precursoren vr gluconeogenese bij mens...............................................................................................31
6.3.1. Lactaat......................................................................................................................................................31
6.3.2. Aminozuren...............................................................................................................................................31
6.3.3. Glycerol.....................................................................................................................................................31
2
, glucose-omzetting nr Sorbitol........................................................................................................................32
6.4. regulatie vd gluconeogenese................................................................................................................. 32
7.1. inleiding................................................................................................................................................ 33
7.2. Oxidatieve fase..................................................................................................................................... 34
7.3. Niet-oxidatieve fase.............................................................................................................................. 34
Box: glucose-6-fosfaat dehydrogenase deficiëntie bij mens.........................................................................34
8.1. inleiding................................................................................................................................................ 35
8.2. Essentiële & niet-essentiële aminozuren................................................................................................ 35
8.3. Synthese v AZ........................................................................................................................................ 36
8.3.1. Novo synthese v niet-essentiëme AZ........................................................................................................36
A) Asparaat & asparagine...............................................................................................................................36
B) Glumataat & glutamine..............................................................................................................................36
C) Serine & glycine..........................................................................................................................................36
Acute lymfoblast leukemie (ALL) bij kinderen kan behandeld worden met asparaginase............................36
8.4. Aminozuurkatabolisme......................................................................................................................... 37
8.4.1. Afbraak vh koolstofskelet v aminozuren..................................................................................................37
Box: fenylketonurie (PKU)= defect in tyrosine vorming.................................................................................37
8.4.2. ureumcyclus ter eliminatie v stikstof........................................................................................................38
8.5. Aminozuurafgeleiden............................................................................................................................ 40
8.5.1. Inleiding....................................................................................................................................................40
8.5.2. Creatine & carnitine..................................................................................................................................40
8.5.3. Synthese & afbraak v haem......................................................................................................................40
a) Synthese.....................................................................................................................................................40
b) Afbraak.......................................................................................................................................................40
8.5.4. Polyaminen...............................................................................................................................................41
8.5.5. Stikstofmonoxide (・NO)..........................................................................................................................41
8.5.6. Neurotransmitters....................................................................................................................................41
9.1. inleiding................................................................................................................................................ 42
9.2. Vetzuursynthese................................................................................................................................... 43
9.2.1. Inleiding....................................................................................................................................................43
9.2.2. Vetzuursynthese volgt niet omgekeerde weg vd ℬ-oxidatie ...................................................................43
9.2.3. De 3 fasen vd vetzuursynthese.................................................................................................................43
9.2.4. Synthese v Malonyl ACP & Acetyl ACP......................................................................................................44
9.2.5. Initiatiereactie v vetzuursynthese.............................................................................................................44
9.2.6. elongatiereacties v vetzuursynthese........................................................................................................44
9.2.7. Activatie v vetzuren (I)..............................................................................................................................44
9.2.8. Vetzuurelongatie -en desaturatie.........................................................................................................45
3
, 9.3. Synthese v triacylglycerolen (triglyceriden) & glycerofosfolipiden..........................................................45
9.4. Synthese v eicosanoïden....................................................................................................................... 45
9.5. synthese v cholesterol........................................................................................................................... 46
9.5.1. stap 1: omzetting v acetyl-CoA nr isopentenyl difosfaat..........................................................................46
9.5.2. stap 2: omzetting v isopentenyl disfosfaat nr squaleen...........................................................................46
9.5.3. stap 3: omzetting v squalene nr cholesterol.............................................................................................46
BOX: regulatie v cholesterolgehaltes.............................................................................................................46
9.6. Oxidatie v vetzuren............................................................................................................................... 47
9.6.1. Inleiding....................................................................................................................................................47
9.6.2. Activatie v vetzuren (II).............................................................................................................................47
9.6.3. ℬ-oxidatie reacties...................................................................................................................................47
9.6.4. Transport v vetzuur acyl CoA id mitochondriën.......................................................................................48
9.6.5. Hoeveel ATP genereert vetzuuroxidatie?.................................................................................................48
9.7. Lokalisatie metabolisme vetten in eukaryoten.......................................................................................48
9.8. Hormonale regulatie v lipidemetabolisme in zoogdieren........................................................................48
9.9. absorptie en mobilisatie v lipiden als brandstof.....................................................................................49
9.9.1. Absorptie v lipiden uit voedin g............................................................................................................49
9.9.2. Lipoproteïnen............................................................................................................................................50
9.9.3. Serum albumine...................................................................................................................................51
9.10. Ketonlichamen als brandstofmoleculen............................................................................................... 51
9.10.1. Ketonlichamen worden gesynthetiseerd id lever...................................................................................51
Lipidenmetabolisme bij suikerziekte..............................................................................................................52
10.1. Inleiding.............................................................................................................................................. 52
10.2. energiebehoefte v organen & weefsels................................................................................................ 52
10.3. Glucosehomeostase............................................................................................................................ 53
10.4. vethomeostase.................................................................................................................................... 54
10.5. Interacties tssn glucose- en triglyceridemetabolisme...........................................................................54
10.6. diabetes= toestand v verstoorde glucosehomeostase..........................................................................55
10.6.1. type I diabetes........................................................................................................................................55
BOX: ontdekking v insuline.............................................................................................................................56
10.7. obesitas= verstoorde triglyceridenhomeostase....................................................................................56
BOX: spelen vetcellen een actieve rol in obesitas & metabool syndroom?..................................................56
BOX: is er een link tssn ontstekingen & obesitas?.........................................................................................56
1. Definitie v metabolisme
4
1.1. Inleiding.................................................................................................................................................. 5
1.2. Metabole paden & metabole flux............................................................................................................ 6
1.2.1. Katabole wegen: 4-fasenplan vr netto energievrijstelling..........................................................................7
1.2.2. Anabole wegen: energie-vereisende processen.........................................................................................7
1.2.3. Amphibole reacties.....................................................................................................................................7
1.3. Cellulaire localisaties v metabole paden..................................................................................................8
1.4. Aangeboren metabole ziektes................................................................................................................. 8
1.4.1. Galactosemie..............................................................................................................................................8
1.4.2. Metabool syndroom/syndroom X...............................................................................................................8
2.1. Van glucose (hexose) nr pyruvaat (triose)................................................................................................ 8
Box 1: vorming v 2,3-BPG in rode bloedcellen...............................................................................................11
2.2. Het lot v pyruvaat: anaëroob metabolisme............................................................................................ 11
2.2.1. Van pyruvaat nr ethanol (gistcel).............................................................................................................11
2.2.2. Van pyruvaat nr lactaat (spiercel)............................................................................................................11
box 2: het melkzuur bij lange afstandslopers.................................................................................................12
2.3. vrije energieveranderingen vd glycolyse................................................................................................ 12
2.4. regulatie vd glycolyse............................................................................................................................ 12
2.4.1. regulatie vh hexose transport...................................................................................................................12
2.4.2. Regulatie v hexokinase.............................................................................................................................13
2.4.3. regulatie v fosfofructokinase-1 (PFK-1)....................................................................................................13
2.4.4. Regulatie v pyruvaatkinase (PK)= feedforward regulatie........................................................................13
2.5. Andere suikers die glycolyse-weg vervoegen......................................................................................... 14
Box 3: metaole stoornis Galactosemie...........................................................................................................14
box 4: lactose-intolerantie, normaal of abnormaal?.....................................................................................14
3.1. mitochondriale koolstofverbranding= tweestapsproces........................................................................15
3.2. Oxidatieve decarboxylering................................................................................................................... 15
3.2.1. Pyruvaatdehydrogenase-complex............................................................................................................15
3.2.2. Regulatie v pyruvaatdehydrogenase........................................................................................................16
3.3. citroenzuurcyclus/Krebs cyclus.............................................................................................................. 16
3.3.1. van acetyl-CoA nr CO2...............................................................................................................................16
3.3.2. Waar komen de elektronen id citroenzuurcylcus?...................................................................................18
3.3.3. Gereduceerde coenzymen kù bevoorrading v ATP verzorgen..................................................................18
4.1. elektronentransport & ATP synthese: inleiding......................................................................................19
1
, 4.2. Hoeveel energie komt vrij bij het elektronentransport?..............................................................................20
4.3. Eiwitcomplexen vd elektronentransportketen.......................................................................................20
4.3.1. Complex I..................................................................................................................................................20
4.3.2. Complex II.................................................................................................................................................21
4.3.3. Complex III................................................................................................................................................21
4.3.4. Complex IV................................................................................................................................................22
4.3.5. Complex V.................................................................................................................................................22
4.4. De respiratoire ontkoppeling................................................................................................................. 22
Inhibtoren vd elektronenstransportketen.....................................................................................................23
4.5. Het gevaar v reactieve zuurstofradicalen....................................................................................................23
Respiratoire supercomplexen........................................................................................................................24
4.6. Mitochondirale ziekten................................................................................................................................24
Box 5: superoxide dismutase (SOD) & ALS.....................................................................................................24
5.1. situering & inleiding.............................................................................................................................. 25
Diabetes/suikerziekte.....................................................................................................................................25
5.2. Glycogenolyse= afbraak v glycogeen...................................................................................................... 26
5.3. Het lot v glucose-1-fosfaat in lever & spieren......................................................................................... 27
5.4. Glycogeensynthese............................................................................................................................... 27
5.5. Regulatie v glycogeenmetabolisme........................................................................................................ 27
5.5.1. Regulatie v glycogeenfosforylase => HORMONAAL.................................................................................28
5.6. Glycogenosen........................................................................................................................................ 28
5.6.1. GSD I/ von Gierke’s ziekte.........................................................................................................................28
5.6.2. GSD II/ziekte v Pompe..............................................................................................................................29
5.6.3. GSD III/ ziekte v Cori.................................................................................................................................29
5.6.4. GDS V/ziekte v McArdle............................................................................................................................29
6.1. inleiding................................................................................................................................................ 29
6.2. Gluconeogenese-enzymen..................................................................................................................... 30
6.2.1. Pyruvaat carboxylase...............................................................................................................................30
6.2.2. Fosfoenol pyruvaat carboxykinase (PEPCK).............................................................................................30
Supermuis.......................................................................................................................................................30
6.2.3. Fructose-1,6-bifosfatase...........................................................................................................................30
6.2.4. Glucose-6-fosfatase..................................................................................................................................30
6.3. Precursoren vr gluconeogenese bij mens...............................................................................................31
6.3.1. Lactaat......................................................................................................................................................31
6.3.2. Aminozuren...............................................................................................................................................31
6.3.3. Glycerol.....................................................................................................................................................31
2
, glucose-omzetting nr Sorbitol........................................................................................................................32
6.4. regulatie vd gluconeogenese................................................................................................................. 32
7.1. inleiding................................................................................................................................................ 33
7.2. Oxidatieve fase..................................................................................................................................... 34
7.3. Niet-oxidatieve fase.............................................................................................................................. 34
Box: glucose-6-fosfaat dehydrogenase deficiëntie bij mens.........................................................................34
8.1. inleiding................................................................................................................................................ 35
8.2. Essentiële & niet-essentiële aminozuren................................................................................................ 35
8.3. Synthese v AZ........................................................................................................................................ 36
8.3.1. Novo synthese v niet-essentiëme AZ........................................................................................................36
A) Asparaat & asparagine...............................................................................................................................36
B) Glumataat & glutamine..............................................................................................................................36
C) Serine & glycine..........................................................................................................................................36
Acute lymfoblast leukemie (ALL) bij kinderen kan behandeld worden met asparaginase............................36
8.4. Aminozuurkatabolisme......................................................................................................................... 37
8.4.1. Afbraak vh koolstofskelet v aminozuren..................................................................................................37
Box: fenylketonurie (PKU)= defect in tyrosine vorming.................................................................................37
8.4.2. ureumcyclus ter eliminatie v stikstof........................................................................................................38
8.5. Aminozuurafgeleiden............................................................................................................................ 40
8.5.1. Inleiding....................................................................................................................................................40
8.5.2. Creatine & carnitine..................................................................................................................................40
8.5.3. Synthese & afbraak v haem......................................................................................................................40
a) Synthese.....................................................................................................................................................40
b) Afbraak.......................................................................................................................................................40
8.5.4. Polyaminen...............................................................................................................................................41
8.5.5. Stikstofmonoxide (・NO)..........................................................................................................................41
8.5.6. Neurotransmitters....................................................................................................................................41
9.1. inleiding................................................................................................................................................ 42
9.2. Vetzuursynthese................................................................................................................................... 43
9.2.1. Inleiding....................................................................................................................................................43
9.2.2. Vetzuursynthese volgt niet omgekeerde weg vd ℬ-oxidatie ...................................................................43
9.2.3. De 3 fasen vd vetzuursynthese.................................................................................................................43
9.2.4. Synthese v Malonyl ACP & Acetyl ACP......................................................................................................44
9.2.5. Initiatiereactie v vetzuursynthese.............................................................................................................44
9.2.6. elongatiereacties v vetzuursynthese........................................................................................................44
9.2.7. Activatie v vetzuren (I)..............................................................................................................................44
9.2.8. Vetzuurelongatie -en desaturatie.........................................................................................................45
3
, 9.3. Synthese v triacylglycerolen (triglyceriden) & glycerofosfolipiden..........................................................45
9.4. Synthese v eicosanoïden....................................................................................................................... 45
9.5. synthese v cholesterol........................................................................................................................... 46
9.5.1. stap 1: omzetting v acetyl-CoA nr isopentenyl difosfaat..........................................................................46
9.5.2. stap 2: omzetting v isopentenyl disfosfaat nr squaleen...........................................................................46
9.5.3. stap 3: omzetting v squalene nr cholesterol.............................................................................................46
BOX: regulatie v cholesterolgehaltes.............................................................................................................46
9.6. Oxidatie v vetzuren............................................................................................................................... 47
9.6.1. Inleiding....................................................................................................................................................47
9.6.2. Activatie v vetzuren (II).............................................................................................................................47
9.6.3. ℬ-oxidatie reacties...................................................................................................................................47
9.6.4. Transport v vetzuur acyl CoA id mitochondriën.......................................................................................48
9.6.5. Hoeveel ATP genereert vetzuuroxidatie?.................................................................................................48
9.7. Lokalisatie metabolisme vetten in eukaryoten.......................................................................................48
9.8. Hormonale regulatie v lipidemetabolisme in zoogdieren........................................................................48
9.9. absorptie en mobilisatie v lipiden als brandstof.....................................................................................49
9.9.1. Absorptie v lipiden uit voedin g............................................................................................................49
9.9.2. Lipoproteïnen............................................................................................................................................50
9.9.3. Serum albumine...................................................................................................................................51
9.10. Ketonlichamen als brandstofmoleculen............................................................................................... 51
9.10.1. Ketonlichamen worden gesynthetiseerd id lever...................................................................................51
Lipidenmetabolisme bij suikerziekte..............................................................................................................52
10.1. Inleiding.............................................................................................................................................. 52
10.2. energiebehoefte v organen & weefsels................................................................................................ 52
10.3. Glucosehomeostase............................................................................................................................ 53
10.4. vethomeostase.................................................................................................................................... 54
10.5. Interacties tssn glucose- en triglyceridemetabolisme...........................................................................54
10.6. diabetes= toestand v verstoorde glucosehomeostase..........................................................................55
10.6.1. type I diabetes........................................................................................................................................55
BOX: ontdekking v insuline.............................................................................................................................56
10.7. obesitas= verstoorde triglyceridenhomeostase....................................................................................56
BOX: spelen vetcellen een actieve rol in obesitas & metabool syndroom?..................................................56
BOX: is er een link tssn ontstekingen & obesitas?.........................................................................................56
1. Definitie v metabolisme
4
