Pathways metabolisme 2016 - 2017 - wikimedica.medica.be · DOC = 11-deoxycorticosterone 11 -hydroxylase NADPH + O 2 + H+ NADP+ + H 2 O 11 -hydroxylase NADPH + O 2 + H+ NADP+ + H 2

PATHWAYS METABOLISME 2017

© Gilles Bossuyt 2017 1

# PRODUCT ENZYM IN UIT

BIOSYNTHESE VAN IMP (DE NOVO)

1. -D-ribose-5-fosfaat

PRPP-synthetase ATP AMP

2. PRPP

= -5-fosforibosyl-1-pyrofosfaat

PRA-synthetase of PRPP-

amidotransferase Gln + H2O Glu + PPi

3. PRA

= -5-fosforibosyl-1-amine

Fosforibosyl glycinamide synthetase Gly + ATP H2O + ADP + Pi

4. GAR

= glycinamide ribonucleotide

Fosforibosyl glycinamide

formyltransferase

H2O + N10-

formyl-FH4 H+ + FH4

5. Formyl-GAR

= -N-formylglycinamide ribonucleotide

Fosforibosylformylglycinamidine

synthetase

Gln + H2O +

ATP Glu + ADP + Pi

6. Formyl-GAMR

= -N-formylglycinamidine

ribonucleotide

Fosforibosylaminoimidazool synthetase ATP H2O + ADP + Pi

7. AIR

= 5-aminoimidazool ribonucleotide

Fosforibosylaminoimidazool

carboxylase CO2

8. Carboxyl-AIR

= 5-aminoimidazool-4-carboxylzuur

ribonucleotide

Fosforibosyl

aminoimidazoolsuccinocarboxamide

synthetase

Asp + ATP H2O + ADP + Pi

9. Succino-AICAR

= 5-amino-imidazool-4-N-

succinocarboxamide ribonucleotide

Adenylsuccinaat lyase Fumaarzuur

10. AICAR

= 5-aminoimidazool-4-carboxamide

ribonucleotide

Fosforibosyl

aminoimidazoolcarboxamide

formyltransferase

N10-formyl-

FH4 FH4

11. Formyl-AICAR

= 5-formamino-imidazool-4-carboxamide

ribonucleotide

IMP cyclohydrolase H2O

12. IMP

= inosine-5’-O-monofosfaat = inosylzuur



BIOSYNTHESE VAN AMP

1. IMP

Adenylsuccinaat synthetase Asp + GTP H2O + GDP + Pi

2. Succino-AMP

Adenylsuccinaat lyase Fumaarzuur

3. AMP

BIOSYNTHESE VAN GMP

1. IMP

IMP dehydrogenase H2O + NAD+ NADH + H+

2. XMP

GMP synthetase Gln + ATP

Glu + AMP +

PPi

3. GMP

BIOSYNTHESE VAN UMP (DE NOVO)

1. Glutamaat

CPS II = Carbamoylfosfaatsynthetase II

2 ATP +

HCO3-

2 ADP + Pi +

H2O

2. Carbamoylfosfaat

ATCase = aspartaattranscarbamoylase Asp Pi

3. N-carbamoylaspartaat

Dihydroorotase H2O

4. Dihydroorotinezuur

Dihydroorotinezuur dehydrogenase NAD+ NADH + H+

5. Orotinezuur

= 6-carboxyluracil

Orotinezuur fosforibosyl transferase PRPP PPi

6. OMP

= orotidylzuur

Orotidylzuur decarboxylase CO2

7. UMP

= uridine-5’-O-monofosfaat = uridylzuur



KATABOLISME VAN PURINEMONONUCLEOTIDEN: VB. AMP

1. AMP

Adenylaat deaminase H2O NH3

2. IMP

Fosfomonoesterase Pi

3. Inosine

Purine nucleoside fosforylase Pi

Ribose-1-

fosfaat

4. Hypoxanthine

Xanthine oxidase O2 + H2O H2O2

5. Xanthine

KATABOLISME VAN URINEZUUR (NIET BIJ PRIMATEN !) (DEEL KATABOLISME VAN PURINEMONONUCLEOTIDEN)

1. Xanthine

Xanthine oxidase O2 + H2O H2O2

2. Urinezuur

Uricase ½ O2 + H2O CO2

3. Allantoine

Allantoinase H2O

4. Allantoinezuur

Allantoicase 2 H2O

2 ureum +

glyoxalaat

5. Ureum

Urease H2O

6. 2 NH3 + CO2

KATABOLISME VAN PYRIMIDINEMONONUCLEOTIDEN: VB. CMP

1. CMP

Fosfomonoesterase = nucleotidase Pi

2. Cytidine

Cytidine deaminase ½ O2 + H2O CO2

3. Uridine

Uridine fosforylase Pi

Ribose-1-

fosfaat

4. Uracil

DPD =

dihydropyrimidinedehydrogenase NADPH + H+ NADP+

5. Dihydrouracil

Dihydropyrimidinecyclohydrolase H2O

6. -ureidopropionzuur

= N-carbamoyl--alanine

Ureidopropionase H2O CO2 + NH3



7. -alanine

Transaminase -ketoglutaarzuur glutaminezuur

8. Malonzuursemialdehyde

CoA H2O

9. Malonyl-CoA

BIOSYNTHESE VAN HEEM

1. Succinyl-CoA

-ALA-synthetase Gly CoA-SH

2. -amino--ketoadipinezuur

-ALA-synthetase

Coënzym vit. B6

codecarboxylase CO2

3. -ALA

= -aminolevulinezuur

ALAD

= -aminolevulinezuur dehydratase 2 -ALA 2 H2O

4. PBG

= porfobilinogeen

Porfobilinogeen deaminase 6 PBG 6 NH3

5. HMB

= hydroxymethylbilaan

Porfobilinogeen deaminase met

uroporfyrinogeen III co-synthase H2O

6. Uroporfyrinogeen III

Uroporfyrinogeen decarboxylase 4 CO2

7. Coproporfyrinogeen III

Coproporfyrinogeen oxidase 2 O2 2 CO2 + 2 H2O2

8. Protoporfyrinogeen IX

Protoporfyrinogeen oxidase 6 H+

9. Protoporfyrine IX

Heem synthetase

= ferrochelatase Fe2+

10. Heem

AFBRAAK VAN HEEM

1. Heem

Heem oxygenase

NADPH + H+ + 2

O2

NADP+ + CO +

Fe3+ + H2O

2. Biliverdine

Biliverdinereductase NADPH + H+ NADP+

3. Bilirubine

Bilirubine uridinedifosfoglucuronaat

transferase

2 UDP-

glucuronzuur 2 UDP

4. Bilirubinediglucuronide



-glucuronidase 8 H+

5. Mesobilirubinogeen

4 H+

6 Urobilinogeen

= stercobilinogeen

½ O2 H2O

7. Urobiline

= stercobiline

-GLUTAMYLCYCLUS

1. Glu

-glutamylcysteïne synthetase ATP + Cys H2O + ADP + Pi

2. -Glu-Cys

Glutathionsynthetase ATP + Gly H2O + ADP + Pi

3. Glutathion

= -Glu-Cys-Gly

-glutamyltranspeptidase AZ

4A. -Glu-AZ

-glutamylcyclotransferase AZ

5A. Oxo-pro

= 5-oxoproline

5-oxoprolinase H2O + ATP ADP + Pi

6A. Glu

4B. Cys-Gly

Dipeptidase H2O

5B. Cys + Gly

UREUMCYCLUS

1. NH3

CPS I

= carbamoylfosfaatsynthetase I 2 ATP + CO2 2 ADP + Pi

2. Carbamoylfosfaat

Ornithinetranscarbamoylase Ornithine Pi

3. Citrulline

Argininosuccinaatsynthase ATP + Asp

AMP + PPi +

H2O

4. Argininosuccinaat

Argininosuccinase Fumaraat

5. Arg

Arginase H2O Ornithine

6. Ureum



BIOSYNTHESE VAN DE GALZUREN

1. Cholesterol

7-hydroxylase O2 + NADPH + H+ H2O + NADP+

2. 7-hydroxycholesterol

3-ol dehydrogenase H+

3. 3-oxo-7α-hydroxycholesterol

4 H+

4A. 3,7-dihydroxycoprostaan

O2

5A. 3,7-dihydroxycoprostaanzuur

-oxidatie CoA

6A. Chenodeoxycholyl-CoA

Gly CoA

7AA. Glycochenodeoxycholzuur

Taurine CoA

7AB. Taurochenodeoxycholzuur

12-hydroxylase

4B. 3-oxo-7α,12α-dihydroxycholesterol

4 H+

5B. 3,7,12-trihydroxycoprostaan

O2

6B. 3,7,12-trihydroxycoprostaanzuur

-oxidatie CoA

7B. Cholyl-CoA

Gly CoA

8BA. Glycocholzuur

Taurine CoA

8BB. Taurocholzuur

-OXIDATIECYCLUS VAN ACYL-COA

1. Acyl-CoA

Acyl-CoA dehydrogenase FAD FADH2

2. (trans-Δ2-) enoyl-CoA

Enoyl-CoA hydratase H2O

3. Hydroxyacyl-CoA

Hydroxyacyl-CoA

dehydrogenase NAD+ NADH + H+

4. Ketoacyl-CoA

Β-ketothiolase CoA Propionyl-CoA



5. Acyl-CoA

SYNTHESE VAN TAURINE

1. Cysteïne

3/2 O2

2. L-cysteïnezuur

CO2

3. Taurine

BIOSYNTHESE VAN HET SCHILDKLIERHORMOON

1. Tyrosine

I0

2. MIT

= 3-monoiodotyrosine

I0

3. DIT

= 3,5-diiodotyrosine

Thyroid peroxidase MIT Ser

4A. T3

= 3,5,3-triiodothyronine

Thyroid peroxidase DIT Ser

4B. T4

= thyroxine

BIOSYNTHESE VAN ADRENALINE

1. Tyrosine

Tyrosine hydroxylase O2 + tetrabiopterine

H2O +

dibiopterine

2. DOPA

= 3,4-dihydroxyphenylalanine

Aromatische 1-aminozuur

decarboxylase CO2

3. Dopamine

= 3,4-dihydroxyphenylethylamine

Dopamine -hydroxylase O2 + ascorbaat

H2O +

dehydroascorbaat

4. Noradrenaline

= 3,4-dihydroxyphenylethanolamine

Phenylethanolamine-N-

methyltransferase

SAM = S-

adenosylmethionine

SAH = S-adenosyl

homocysteïne

5. Adrenaline



KATABOLISME VAN ADRENALINE

1. Adrenaline

COMT

= catechol-O-methyltransferase

SAM = S-

adenosylmethionine

SAH = S-adenosyl

homocysteïne

2A. Metadrenaline

MAO

= monoamine oxidase H2O + FAD FADH2 + NH3

3A. 3-methoxy-4-hydroxymandeline

aldehyde

MAO H2O + FAD FADH2 + NH3

4AA. VMA, vanilmandelinezuur

= 3-methoxy-4-

hydroxymandelinezuur

Aldehyde reductase NADH + H+ NAD+

4AB. 3-methoxy-4-hydroxyfenylglycol

…

5AB. Vanillinaat

MAO H2O + FAD FADH2 + NH3

2B. 3,4-dihydroxymandelinezuur

COMT SAM SAH

3B. VMA

KATABOLISME VAN DOPAMINE

1. Dopamine

COMT

= catechol-O-methyltransferase

SAM = S-

adenosylmethionine

SAH = S-adenosyl

homocysteïne

2. 3-methoxy-dopamine

MAO

= monoamine oxidase H2O + FAD FADH2 + NH3

3. Homovanillinaat

BIOSYNTHESE VAN PREGNENOLONE

1. Cholesterol

“mixed-function” oxidase NADPH + O2 + H+ NADP+ + H2O

2. 20-hydroxycholesterol

“mixed-function” oxidase NADPH + O2 + H+ NADP+ + H2O

3. 20,22-dihydroxycholesterol

Desmolase “mixed-function”

oxidase NADPH + O2 + H+

NADP+ + H2O +

Isocaproaldehyde

4. Pregnenolone



BIOSYNTHESE VAN CORTISOL

1. Pregnenolone


2A. Progesterone

17-hydroxylase NADPH + O2 + H+ NADP+ + H2O


2B. 17-hydroxypregnenolone


3. 17-hydroxyprogesterone


4. 11-deoxycortisol


5. Cortisol

BIOSYNTHESE VAN CORTICOSTERONE

1. Pregnenolone


2. Progesterone


3A. DOC

= 11-deoxycorticosterone



3B. 11-hydroxyprogesterone


4. Corticosterone

BIOSYNTHESE VAN ALDOSTERONE

1. Corticosterone


2. 18-hydroxycorticosterone

H+

3. Aldosterone

BIOSYNTHESE VAN SEROTONINE

1. Tryptofaan

Tryptofaan hydroxylase

O2 +

tetrahydrobiopterine

H2O +

dihydrobiopterine

2. 5-hydroxytryptofaan

Aromatisch aminozuur

decarboxylase CO2

3. Serotonine



AFBRAAK VAN SEROTONINE

1. Serotonine

Monoamine oxidase H2O + FAD NH3 + FADH2

2. 5-hydroxy-indool-3-acetaldehyde

Aldehyde dehydrogenase NAD+ + H2O NADH + H+

3. 5-hydroxy-indool-3-azijnzuur

BIOSYNTHESE VAN MELATONINE

1. Serotonine

N-acetyltransferase Acetyl-CoA CoA

2. N-acetylserotonine

O-methyltransferase SAM SAH

3. Melatonine

GABA-SHUNT

1. α-ketoglutaraat

Glutamaat dehydrogenase NH4+ + NADPH + H+ NADP+ + H2O

2. Glutamaat

Glutamaat decarboxylase CO2

3. GABA

= γ-aminoboterzuur

GABA transaminase H2O NH4+ + 2 H+

4. Succinaat semialdehyde

Succinaat semialdehyde

dehydrogenase NAD+ + H2O NADH + 2 H+

5. Succinaat

BIOSYNTHESE VAN CREATININE

1. Arginine

Arginine glycine aminidase Glycine Ornithine

2. Guanidinio-acetaat

Guanidinio-acetaat

methyltransferase SAM + ATP SAH + ADP

3. Creatine-fosfaat

[spontaan] Pi

4. Creatinine



GLYCOLYSE

1. Glucose

Hexokinase ATP ADP + H+

2. Glucose-6-fosfaat

GPI

= fosfoglucose isomerase

3. Fructose-6-fosfaat

FFK

= fosfofructokinase ATP ADP + H+

4. Fructose-1,6-bisfosfaat

Aldolase

5. GAP + DHAP

= glyceraldehyde-3-fosfaat +

dihydroxyaceton fosfaat

TIM

= triofosfaatisomerase

6. 2 GAP

GAPDH

= glyceraldehyde-3-fosfaat

dehydrogenase

2 NAD+ + 2 Pi 2 NADH + 2 H+

7. 2 1,3-BPG

= 1,3-bisfosfoglyceraat

PGK

= fosfoglyceraatkinase 2 ADP + 2 H+ 2 ATP

8. 2 3-fosfoglyceraat

PGM

= fosfoglyceraatmutase

9. 2 2-fosfoglyceraat

Enolase 2 H2O

10. 2 PEP

= fosfoenolpyruvaat

Pyruvaat kinase 2 ADP + 2 H+ 2 ATP

11. 2 pyruvaat

PYRUVAAT → ETHANOL

1. Pyruvaat

Pyruvaat decarboxylase

Thiamine

pyrofosfaat

Thiamine

pyrofosfaat

2. Acetaldehyde

Alcohol dehydrogenase Zn2+ Zn2+

3. Ethanol



FRUCTOSE-1-FOSFAAT PATHWAY

1. Fructose

Fructokinase ATP ADP + H+


Fructose-1-fosfaat aldolase DHAP

3. Glyceraldehyde

Triosekinase ATP ADP + H+

4. GAP

GALACTOSE PATHWAY

1. Galactose

Galactokinase ATP ADP + H+

2. Galactose-1-fosfaat

Galactose 1-fosfaat uridyltransferase UDP-glucose

3A. UDP-galactose

UDP-galactose 4-epimerase

4A. UDP-glucose

3B. Glucose-1-fosfaat

Fosfoglucomutase

4B. Glucose-6-fosfaat

GLUCONEOGENESE

1. Pyruvaat

Pyruvaat carboxylase ATP + HCO3- ADP + Pi

2. Oxaloacetaat

Malaat dehydrogenase NADH + H+ NAD+

3. Malaat

PEP carboxykinase GTP GDP + CO2

4. PEP

= fosfoenolpyruvaat

Enolase H2O

5. 2-fosfoglyceraat

PGM

= fosfoglyceraat mutase

6. 3-fosfoglyceraat

PGK

= fosfoglyceraat kinase ATP ADP

7. 1,3-bisfosfoglyceraat

GAPDH

= glyceraldehyde-3-fosfaat

dehydrogenase

NADH + H+ NAD+ + Pi

8. GAP + DHAP



= glyceraldehyde-3-fosfaat +

dihydroxyaceton fosfaat

Aldolase

9. Fructose-1,6-bisfosfaat

Fructose-1,6-bisfosfatase H2O Pi


GPI

= fosfoglucose isomerase


Glucose-6-fosfatase H2O Pi

12. Glucose

CITROENZUURCYCLUS

1. Pyruvaat

Pyruvaat dehydrogenase NAD+ + CoA

NADH + H+ +

CO2

2. Acetyl-CoA

Citraatsynthase Oxaloacetaat CoA

3. Citraat

Acitonase

4. Isocitraat

Isocytraat dehydrogenase NAD+ NADH + CO2

5. -ketoglutaraat

-ketoglutaraat dehydrogenase NAD+ + CoA NADH + CO2

6. Succinyl-CoA

Succinyl-CoA synthetase ADP + Pi ATP + CoA

7. Succinaat

Succinaat dehydrogenase FAD FADH2

8. Fumaraat

Fumarase H2O

9. Malaat

Malaat dehydrogenase NAD+ NADH + H+

10. Oxaloacetaat



PPPATHWAY


Glucose-6-fosfaat dehydrogenase NADP+ NADPH + H+

2. Fosfoglucono-𝛿-lacton

Lactonase H2O

3. Fosfogluconaat

Fosfogluconaat dehydrogenase NADP+

NADPH + H+ +

CO2

4. Ribulose-5-fosfaat

Fosfopentose isomerase

5A. Ribose-5-fosfaat

Fosfopentose epimerase

5B. Xylulose-5-fosfaat Ribose-5-fosfaat

Transketolase

6B. Sedoheptulose-7-fosfaat + GAP

Transaldolase

Fructose-6-

fosfaat

7B. Erythrose-4-fosfaat

Transketolase

Xylulose-5-

fosfaat

8B. Fructose-6-fosfaat + GAP

VETZUURSYNTHESE

1. Acetyl-CoA

Acetyl transacylase ACP CoA

2A. Acetyl-ACP

Acetyl-CoA carboxylase CO2

2B. Malonyl-CoA

Malonyl transacylase ACP CoA

2B. Malonyl-ACP

Acetyl-malonyl-ACP condensing enzym

Acetyl-ACP +

malonyl-ACP ACP

3. Acetoacetyl-ACP

β-ketoacyl-ACP reductase NADPH + H+ NADP+

4. 3-hydroxybuturyl-CoA

Hydroxyacyl-ACP dehydratase H2O

5. Crotonyl-CoA

Enoyl-ACP reductase NADPH + H+ NADP+

6. Butyryl-CoA

[na 7 cycli] Thio-esterase

Palmitaat



AFBRAAK VAN VERTAKTE AMINOZUREN (BV. LEUCINE)

1. Leucine

[transaminatie] NH4+

2. α-ketoisocapronzuur

Vertakte keten α-ketozuur

dehydrogenase CoA CO2

3. Isovaleryl-CoA

[dehydrogenatie] NAD+ NADH + H+

4. β-methylcrotonyl-CoA

[carboxylatie] CO2

5. β-methylglutaconyl-CoA

[hydratatie] H2O

6. HMG-CoA

= 3-hydroxy-3-methylglutaryl-CoA

HMG-CoA klieving enzyme Acetyl-CoA

7. Acetoacetaat

AFBRAAK VAN AROMATISCHE AMINOZUREN (BV. FENYLALANINE)

1. Fenylalanine

Fenylalanine hydroxylase Tetrabiopterine Dibiopterine

2. Tyrosine

[transaminatie] NH4+

3. p-hydroxyfenylpyruvaat

p-hydroxyfenylpyruvaat hydroxylase

4. Homogentisinezuur

Homogentisinezuur oxidase

5. …

…

6. Fumaraat + ocetoacetaat

AFBRAAK VAN PROPIONYL-COA

1. Propionyl-CoA

Propionyl-CoA carboxylase ATP + CO2 ADP + Pi

2. Methylmalonyl-CoA

Methylmalonyl-CoA isomerase

3. Succinyl-CoA

BIOSYNTHESE VAN CYSTEÏNE

1. Homocysteïne

Cystathionine β-synthase Ser

2. Cystathionine



Cystathioninase

α-

ketobutyraat +

NH4+

3. Cysteïne

BIOSYNTHESE VAN NO

1. Arginine

NOS

= NO synthase NADPH + H+ + O2 NADP+ + H2O

2. N-hydroxy-arginine

NOS NADPH + O2

NADP+ + H2O +

citrulline

3. NO

BIOSYNTHESE VAN CHOLESTEROL

1. 2 acetyl-CoA

β-ketothiolase CoA

2. Acetoacetyl-CoA

Hydroxymethylglutaryl-CoA synthase

H2O + acetyl-

CoA CoA

3. HMG-CoA

= 3-hydroxy-3-methylglutaryl-CoA

Hydroxymethylglutaryl-CoA reductase

4. Mevalonzuur

…

5. Isopreen

…

6. Cholesterol

Documents

Pathways metabolisme 2016 - 2017 - wikimedica.medica.be · DOC = 11-deoxycorticosterone 11 -hydroxylase NADPH + O 2 + H+ NADP+ + H 2 O 11 -hydroxylase NADPH + O 2 + H+ NADP+ + H 2