Metabolisme en metabole
regeling
Table of Contents
Afkortingenlijst...................................................................................3
1. Biomoleculen............................................................................4
Suikers (koolhydraten)........................................................................4
Lipiden...............................................................................................5
Proteïnen............................................................................................5
Nucleïnezuren.....................................................................................5
2. Metabolisme............................................................................. 5
Stofwisselingsziekten en metabolietherstel..........................................7
3. Cellulaire opbouw en afbraak van glucose in glycolyse................9
Fluxcontrolerende stappen............................................................................................10
Verdere metabolisatie pyruvaat.........................................................11
Metabolisme fructose en galactose.....................................................11
Fructose......................................................................................................................... 11
Galactose....................................................................................................................... 11
Verdieping: Complicaties bij diabetes; rol voor glycolyse.....................12
Verstoringen fructoseMtb..................................................................14
Erfelijke Frct-intolerantie: fructosemie...........................................................................14
Fructosurie..................................................................................................................... 15
Verstoringen galactoseMtb................................................................15
Types galactosemie....................................................................................................... 15
Mtb gevolgen defecten Leloir route...............................................................................15
Verdieping: Kritische ziekte...............................................................16
4. Mitochondriale C-verbranding..................................................16
Regeling PDH-complex................................................................................................... 17
Regeling Krebscyclus..................................................................................................... 18
Kataplerose Krebscyclus................................................................................................ 18
Anaplerose Krebscyclus.................................................................................................18
Hoe geraken VZ in de mt...............................................................................................18
β-oxidatie VZ in mt; telkens 2 C-atomen eraf via acetyl-CoA.........................................19
β-oxidatie VZ in peroxisomen; enkele verschillen..........................................................19
Oxidatie van ketonlichamen.......................................................................................... 20
Oxidatie van AZ............................................................................................................. 20
Verdieping: Peroxisomale ziektes, andere metabole paden..................20
Peroxisoombiogenesestoornissen..................................................................................20
Enkelvoudige enzymdefecten........................................................................................20
,5. Oxidatieve fosforylering..........................................................21
Verdieping: Mitochondriale dysfunctie................................................23
Mitochondriale ziekten: erfelijke defecten mt genoom..................................................23
Mitochondriale ziekten: erfelijke defecten nucleaire genoom........................................23
Superoxide dismutase................................................................................................... 23
ALS................................................................................................................................ 23
6. Glycogeen, gluconeogenese en ketogenese..............................23
Glycogenolyse...................................................................................24
Reciproke regeling synthese/afbraak glycogeen..................................24
Gluconeogenese................................................................................24
Reciproke regeling gluconeogenese en glycolyse................................24
Insuline vs Glucagon pathways......................................................................................25
Ketogenese.......................................................................................25
Verdieping: glycogenosen (glycogeenstapelingsziektes)......................26
7. Vetzuur- en cholesterolsynthese, pentosefosfaatweg................27
1 - Vetzuursynthese en triglyceriden..................................................27
2 – Cholesterolsynthese.....................................................................30
3 – Pentosefosfaatweg generator NADPH...........................................31
4 – Lipidentransport in menselijk bloed...............................................33
Verdieping 7-8............................................................................ 34
1. VZ-synthese en PPW in cancercellen...............................................34
2. PPW in rbc.....................................................................................35
3. G6P-dehydrogenase-deficiëntie......................................................35
4. Leververvetting door alcohol/voeding: (N)AFLD...............................35
5. Dislipidemie en atherosclerose.......................................................36
6. Lysomale stofwisselingsziektes......................................................37
7. Androgenitaal syndroom................................................................37
8. Hormoongevoelige cancer..............................................................38
9. Bijwerkingen glucocorticoid-behandeling........................................38
10. NSAIDs........................................................................................39
8. Vetzuur- en cholesterolafgeleiden............................................39
1. Inleiding........................................................................................39
2. Membraanlipiden...........................................................................39
3. Lipidenboodschappers...................................................................40
4. Cytochroom P450-systeem en detoxificatie........................................41
5. Afgeleiden van cholesterol.............................................................42
,9. Aminozuren............................................................................44
Verdieping: van AZ afgeleide moleculen.............................................46
Ergogene aminen: Creatine – Carnitine – Carnosine......................................................46
Heemsynthese............................................................................................................... 47
Afbraak en eliminatie heem........................................................................................... 48
Icterus = geelzucht........................................................................................................ 48
10. Nucleotiden..........................................................................49
Verdieping: Cancermetabolisme.........................................................51
11. Voeding................................................................................ 53
1. Malnutritie/gezonde voeding..........................................................53
2. Dagelijkse energiebehoefte............................................................53
3. Evenwichte voeding.......................................................................54
4. Macronutriënten............................................................................55
5. Mineralen......................................................................................56
6. Vitamines......................................................................................58
12. Lichaam................................................................................ 62
1. Energiebehoefte organen...............................................................62
2. Glucose- en triglyceridenhomeostase..............................................62
3. Vasten..........................................................................................64
4. Fysieke inspanning........................................................................64
5. Diabetes........................................................................................65
6. Obesitas........................................................................................66
Afkortingenlijst
ACP: Acyl Carrier Protein
ADH: aanbevolen dagelijkse hoeveelheid
AGE: Advanced glycation end-products
ANT: Adenine nucleotide translocator
Asp: Aspartaat (Asparaginezuur)
ATGL: Adipocyten-TGlipase
CAF: Cancer-associated fibroblast
CD36: Cluster of differentiation 36 (FAT)
DAG: Diacylglycerol
DH: Dehydrogenase
DHA: Docosahexaeenzuur
()DL: Density lipoprotein
E: energie
EPA: Eicosapentaeenzuur
, FAD: Flavine-adenodinucleotide
FAS: Fatty Acid Synthase
FAT: Fatty acid translocase (CD36)
Glu: Glutamaat (Glutaminezuur)
GCK: Glucokinase
HGD: Homogentisaat dioxygenase
HK: HexoKinase
HSL: Hormone-sensitive lipase
IAPP: Islet Amyloid PolyPeptide
IPPP: Isopentenylpyrofosfaat
LPL: LipoProteïneLipase
MAG: MonoAcylGlycerol
Mbrn: membraan
NAD: Nicotinamide-adenodinucleotide
NAFLD: Non-Alcoholic Fatty Liver Disease
P: fosfaat
PEP: PhosphoEnolPyruvaat
PFK: PhosphoFructoKinase
PPW: Pentosefosfaatweg
PTM: Post Translationele Modificatie
PYY: Peptide YY (3-36)
ROS: Reactieve O-Species
RPE: ribulose-5-fosfaat-3-epimerase
SAM: S-adenosyl-methionine
SCAP: SREBP Cleavage Activating Protein
TPP: ThiaminePyroPhosfaat
VZ: vetzuur
Regulatiemechanismen Gluc/Insuline glycolyse/gluconeogenese/frct-6biP… !
1. Biomoleculen
• De verschillende biomoleculen en hun functies
• Het verschil tussen paraloge en ortologe genen en belangrijke voorbeelden
hiervan
• Het concept polymorfisme
Suikers (koolhydraten)
Monosachariden -glycosidebindingen-> di/oligo/polysachariden
Niet gecodeerd, wel enzymen die suikers aanmaken
meest abundante biomolecuul op aarde
energiebron, structuurgevend
L-isomeer -> HO-groep links
Sucrose (Glu-Fru) ivm cariës en obesitas
regeling
Table of Contents
Afkortingenlijst...................................................................................3
1. Biomoleculen............................................................................4
Suikers (koolhydraten)........................................................................4
Lipiden...............................................................................................5
Proteïnen............................................................................................5
Nucleïnezuren.....................................................................................5
2. Metabolisme............................................................................. 5
Stofwisselingsziekten en metabolietherstel..........................................7
3. Cellulaire opbouw en afbraak van glucose in glycolyse................9
Fluxcontrolerende stappen............................................................................................10
Verdere metabolisatie pyruvaat.........................................................11
Metabolisme fructose en galactose.....................................................11
Fructose......................................................................................................................... 11
Galactose....................................................................................................................... 11
Verdieping: Complicaties bij diabetes; rol voor glycolyse.....................12
Verstoringen fructoseMtb..................................................................14
Erfelijke Frct-intolerantie: fructosemie...........................................................................14
Fructosurie..................................................................................................................... 15
Verstoringen galactoseMtb................................................................15
Types galactosemie....................................................................................................... 15
Mtb gevolgen defecten Leloir route...............................................................................15
Verdieping: Kritische ziekte...............................................................16
4. Mitochondriale C-verbranding..................................................16
Regeling PDH-complex................................................................................................... 17
Regeling Krebscyclus..................................................................................................... 18
Kataplerose Krebscyclus................................................................................................ 18
Anaplerose Krebscyclus.................................................................................................18
Hoe geraken VZ in de mt...............................................................................................18
β-oxidatie VZ in mt; telkens 2 C-atomen eraf via acetyl-CoA.........................................19
β-oxidatie VZ in peroxisomen; enkele verschillen..........................................................19
Oxidatie van ketonlichamen.......................................................................................... 20
Oxidatie van AZ............................................................................................................. 20
Verdieping: Peroxisomale ziektes, andere metabole paden..................20
Peroxisoombiogenesestoornissen..................................................................................20
Enkelvoudige enzymdefecten........................................................................................20
,5. Oxidatieve fosforylering..........................................................21
Verdieping: Mitochondriale dysfunctie................................................23
Mitochondriale ziekten: erfelijke defecten mt genoom..................................................23
Mitochondriale ziekten: erfelijke defecten nucleaire genoom........................................23
Superoxide dismutase................................................................................................... 23
ALS................................................................................................................................ 23
6. Glycogeen, gluconeogenese en ketogenese..............................23
Glycogenolyse...................................................................................24
Reciproke regeling synthese/afbraak glycogeen..................................24
Gluconeogenese................................................................................24
Reciproke regeling gluconeogenese en glycolyse................................24
Insuline vs Glucagon pathways......................................................................................25
Ketogenese.......................................................................................25
Verdieping: glycogenosen (glycogeenstapelingsziektes)......................26
7. Vetzuur- en cholesterolsynthese, pentosefosfaatweg................27
1 - Vetzuursynthese en triglyceriden..................................................27
2 – Cholesterolsynthese.....................................................................30
3 – Pentosefosfaatweg generator NADPH...........................................31
4 – Lipidentransport in menselijk bloed...............................................33
Verdieping 7-8............................................................................ 34
1. VZ-synthese en PPW in cancercellen...............................................34
2. PPW in rbc.....................................................................................35
3. G6P-dehydrogenase-deficiëntie......................................................35
4. Leververvetting door alcohol/voeding: (N)AFLD...............................35
5. Dislipidemie en atherosclerose.......................................................36
6. Lysomale stofwisselingsziektes......................................................37
7. Androgenitaal syndroom................................................................37
8. Hormoongevoelige cancer..............................................................38
9. Bijwerkingen glucocorticoid-behandeling........................................38
10. NSAIDs........................................................................................39
8. Vetzuur- en cholesterolafgeleiden............................................39
1. Inleiding........................................................................................39
2. Membraanlipiden...........................................................................39
3. Lipidenboodschappers...................................................................40
4. Cytochroom P450-systeem en detoxificatie........................................41
5. Afgeleiden van cholesterol.............................................................42
,9. Aminozuren............................................................................44
Verdieping: van AZ afgeleide moleculen.............................................46
Ergogene aminen: Creatine – Carnitine – Carnosine......................................................46
Heemsynthese............................................................................................................... 47
Afbraak en eliminatie heem........................................................................................... 48
Icterus = geelzucht........................................................................................................ 48
10. Nucleotiden..........................................................................49
Verdieping: Cancermetabolisme.........................................................51
11. Voeding................................................................................ 53
1. Malnutritie/gezonde voeding..........................................................53
2. Dagelijkse energiebehoefte............................................................53
3. Evenwichte voeding.......................................................................54
4. Macronutriënten............................................................................55
5. Mineralen......................................................................................56
6. Vitamines......................................................................................58
12. Lichaam................................................................................ 62
1. Energiebehoefte organen...............................................................62
2. Glucose- en triglyceridenhomeostase..............................................62
3. Vasten..........................................................................................64
4. Fysieke inspanning........................................................................64
5. Diabetes........................................................................................65
6. Obesitas........................................................................................66
Afkortingenlijst
ACP: Acyl Carrier Protein
ADH: aanbevolen dagelijkse hoeveelheid
AGE: Advanced glycation end-products
ANT: Adenine nucleotide translocator
Asp: Aspartaat (Asparaginezuur)
ATGL: Adipocyten-TGlipase
CAF: Cancer-associated fibroblast
CD36: Cluster of differentiation 36 (FAT)
DAG: Diacylglycerol
DH: Dehydrogenase
DHA: Docosahexaeenzuur
()DL: Density lipoprotein
E: energie
EPA: Eicosapentaeenzuur
, FAD: Flavine-adenodinucleotide
FAS: Fatty Acid Synthase
FAT: Fatty acid translocase (CD36)
Glu: Glutamaat (Glutaminezuur)
GCK: Glucokinase
HGD: Homogentisaat dioxygenase
HK: HexoKinase
HSL: Hormone-sensitive lipase
IAPP: Islet Amyloid PolyPeptide
IPPP: Isopentenylpyrofosfaat
LPL: LipoProteïneLipase
MAG: MonoAcylGlycerol
Mbrn: membraan
NAD: Nicotinamide-adenodinucleotide
NAFLD: Non-Alcoholic Fatty Liver Disease
P: fosfaat
PEP: PhosphoEnolPyruvaat
PFK: PhosphoFructoKinase
PPW: Pentosefosfaatweg
PTM: Post Translationele Modificatie
PYY: Peptide YY (3-36)
ROS: Reactieve O-Species
RPE: ribulose-5-fosfaat-3-epimerase
SAM: S-adenosyl-methionine
SCAP: SREBP Cleavage Activating Protein
TPP: ThiaminePyroPhosfaat
VZ: vetzuur
Regulatiemechanismen Gluc/Insuline glycolyse/gluconeogenese/frct-6biP… !
1. Biomoleculen
• De verschillende biomoleculen en hun functies
• Het verschil tussen paraloge en ortologe genen en belangrijke voorbeelden
hiervan
• Het concept polymorfisme
Suikers (koolhydraten)
Monosachariden -glycosidebindingen-> di/oligo/polysachariden
Niet gecodeerd, wel enzymen die suikers aanmaken
meest abundante biomolecuul op aarde
energiebron, structuurgevend
L-isomeer -> HO-groep links
Sucrose (Glu-Fru) ivm cariës en obesitas
