Gluconeogenese


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Inleiding:

Gluconeogenese : de vorming van glucose uit eiwitten en vetten onder invloed van het hormoon cortisol (hydrocortison ) uit de bijnierschors.

Hoewel de  gluconeogenese niet exact het omgekeerde is van de glycolyse , deelt de gluconeogenese veel enzymen van de glycolyse en de citroenzuurcyclus.

De gluconeogenese voorziet in glucose wanneer er sprake is van schaarsheid aan glucose in de cellen
( met name de cellen in het brein ) en wanneer de melkzuur -( lactaat ) spiegel stijgt. Glucose wordt alleen gevormd in de lever en de nieren , omdat deze het enzym glucose-6-fosfatase bevatten die glucose-6-fosfaat moeten omzetten tot glucose.

Glucose is essentieel voor het brein, zenuwstelsel en andere weefsels. Het menselijk lichaam heeft ongeveer 160 gram glucose per dag nodig. Het brein heeft hiervan 120 gram nodig.

De gluconeogenese volgt 7 stappen van de glycolyse in omgekeerde volgorde. De drie onomkeerbare stappen in de glycolyse ( pyruvate kinase, phosphofructokinase en hexokinase ) worden in de gluconeogenese door andere enzymen uitgevoerd.( pyruvate carboxylase en PEP-carboxy kinase; fructose bis-phosphatase en glucose-6-phosphatase ).

Regulatie die bepaald of glycolyse of gluconeogenese plaatsvindt is essentieel. Glycolyse levert 2 ATP op; terwijl gluconeogese het equivalent van 4 ATP verbruikt.

Het hormoon glucagon signaleert een te laag glucose gehalte in het bloed , laat de glycolyse stoppen en activeert de gluconeogenese.



De enzymen:

De reacties zijn enzym gekatalyseerd, waarbij de volgende enzymen een rol spelen:

 

  1. Pyruvate Carboxylase

    Synoniemen: Pyruvic carboxylase

    ExPASy: EC 6.4.1.1

    ATP + pyruvate + HCO3 -  <> ADP + phosphate + oxaloacetate

    C10H16N5O13P3 + C3H4O3 + CHO3-  <=> C10H15N5O10P2 + H3O4P + C4H4O5

    Human Genetic Disease:

    Pyruvate Carboxilase Deficiency

    Synoniemen: PC Deficiency;  Ataxia with lactic acidosis II;  Leigh Syndrome due to Pyruvate Carboxylase Def.; Leigh Necrotizing Encephalopathy due to pyruvate carboxylase deficiency

    OMIM: 266150

    OMIM: Clinical Synopsis

    e-Medicine: Pyruvate Carboxylase Deficiency


     
  2. Phosphoenolpyruvate carboxykinase (GTP)

    Synoniemen: Phosphopyruvate carboxylase, Phosphoenolpyruvate carboxylase, Phosphoenolpyruvate carboxykinase, PEP carboxykinase, PEPCK.

    ExPASY: EC 4.1.1.32

    GTP + oxaloacetate <> GDP + phosphoenolpyruvate + CO2

    C10H16N5O14P3 + C4H4O5 <=> C10H15N5O11P2  + C3H5O6P + CO2

    Human Genetic Disease:

    Phosphoenolpyruvate carboxykinase deficiency ( PEPCK deficiency )

    OMIM: 261650

    OMIM: Clinical Synopsis



     
  3. Phosphopyruvate hydratase

    Synoniemen: Enolase,  2-phosphoglycerate dehydratase

    ExPASy: EC 4.2.1.11

    2-phospho-D-glycerate <=> phosphoenolpyruvate +  H2O

    C3H7O7P <=>   C3H5O6P + H2O


     
  4. Phosphoglycerate mutase 

    Synoniemen:
    Phosphoglycerate phosphomutase, Phosphoglyceromutase, PGAM.

    ExPASy: EC 5.4.2.1

    2-phospho-D-glycerate +  2,3-diphosphoglycerate <=> 3-phospho-D-glycerate +  2,3-diphosphoglycerate

    C3H7O7P <=> C3H7O7P

    Human Genetic Disease(s):

    Phosphoglycerate mutase deficiency

    OMIM: Myopathy due to phosphoglycerate mutase deficiency

    OMIM: Clinical synopsis


     
  5. Phosphoglycerate kinase

    ExPASy: EC 2.7.2.3

    ATP +  3-phospho-D-glycerate <=>  ADP +  3-phospho-D-glyceroyl phosphate

    C10H16N5O13P3 + C3H7O7P <=> C10H15N5O10P2 + C3H8O10P2 

    Human Genetic Disease(s):

    Phosphoglycerate kinase deficiŽntie

    OMIM: 311800

    OMIM: Clinical Synopsis


     

  6. Glyceraldehyde 3-phosphate dehydrogenase ( phosphorylating ).

    Enzym synoniemen: NAD-dependent glyceraldehyde-3-phosphate dehydrogenase, Triosephosphate dehydrogenase, GAPDH.

    ExPASy: EC 1.2.1.12

    D-glyceraldehyde 3-phosphate +  phosphate +  NAD+ <=> 3-phospho-D-glyceroyl phosphate +  NADH

    C3H7O6P +
    H3O4P + C21H28N7O14P2 <=> C3H8O10P2  + C21H29N7O14P2


     
  7. Triose phosphate isomerase

    Enzym synoniemen: Triosephosphate mutase, Triose phosphoisomerase, Phosphotriose isomerase.

    ExPASy: EC 5.3.1.1

    D-glyceraldehyde 3-phosphate <=> glycerone phosphate

    C3H7O6P <=>
    C3H7O6P

    Human Genetic Disease:

    Triosephosphate isomerase deficiency

    OMIM: Triosephosphate isomerase deficiency ( Hemolytic anemia due to triosephosphate isomerase deficiency )

    OMIM: Clinical synopsis



     
  8. Fructose biphosphate aldolase

    Enzym synoniemen: Aldolase,  Fructose-1,6-bisphosphate triosephosphate-lyase.

    ExPASy: EC 4.1.2.13

    D-fructose 1,6-bisphosphate <=> glycerone phosphate  +  D-glyceraldehyde 3-phosphate

    C6H14O12P2 <=> C3H7O6P + C3H7O6P

    Human Genetic Disease(s):

    Heriditaire fructose intolerantie

    Synoniemen: Fructosemie;   fructose-1-phosphate aldolase deficiency;   

    Fructose-1,6-biphosphate aldolase  deficiency; Aldolase B deficiency.

    OMIM: 229600   (
    Fructose intolerance )

    Omim: Clinical Synopsis

    e-Medicine: Fructose 1-Phosphate Aldolase Deficiency (Fructose Intolerance)

    Aldolase A Deficiency

    Synoniemen: erythrocyte Aldolase Deficiency with nonspherocytic hemolytic anemia

    OMIM: 103850   ( Hemolytic anemia due to aldolase A deficiency )

    Omim: Clinical Synopsis


     

  9. Fructose-bisphosphatase

    Synoniemen: Fructose-1,6-bisphosphatase, Hexosediphosphatase

    ExPASy: EC 3.1.3.11

    D-fructose 1,6-bisphosphate +  H2O <=> D-fructose 6-phosphate +  phosphate

    C6H14O12P2 + H2O <=> C6H13O9P + H3O4P

    Human Genetic Disease(s):

    Fructose-1,6-bisphosphatase deficiency

    OMIM: 229700

    OMIM: Clinical Synopsis



     

  10. Glucose-6-phosphate isomerase 

    Synoniemen voor dit enzym zijn: Phosphoglucose isomerase, Phosphohexose isomerase, Phosphohexomutase, Oxoisomerase, Hexosephosphate isomerase, Hexose monophosphate isomerase, Phosphosaccharomutase, Phosphoglucoisomerase, Phosphohexoisomerase.

    ExPASy: EC 5.3.1.9

    D-glucose 6-phosphate <=> D-fructose 6-phosphate

    C6H13O9P <=> C6H13O9P

    Human Genetic Disease:

    Glucose-6-phosphate isomerase deficiency

    OMIM: Hemolytic anemia due to phosphoglucose isomerase deficiency


    OMIM: Clinical Synopsis


     

  11. Glucose-6-phosphatase

    ExPASy: EC 3.1.3.9

    D-glucose 6-phosphate + H2O <=> D-glucose + phosphate

    C6H13O9P + H2O <=> C6H12O6 + H3O4P

    Human Genetic Disease:

    Glycogen Storage Disease I

    Synoniemen: Von Gierke Disease; Glucose-6-phosphatase deficiency; Hepatorenal Glycogenosis

    OMIM: 232200

    OMIM: Clinical Synopsis

    e-Medicine: Glycogen Storage Disease Type I

    Who Named It?:  Edgar Otto Conrad von Gierke

 

 

Overzicht Gluconeogenese:

 

GenomeNet: Pyruvate (2-Oxopropanoate; 2-Oxopropanoic acid ) GenomeNet: oxaloacetate (2-oxobutanedioic acid) GenomeNet: Phosphoenolpyruvate ( PEP ) GenomeNet: 2-Phospho-D-glycerate (D-Glycerate 2-phosphate) GenomeNet: 3-Phospho-D-glycerate ( D-Glycerate 3-phosphate ) GenomeNet: 3-Phospho-D-glyceroyl phosphate ( 1,3-Bisphospho-D-glycerate) GenomeNet: D-Glyceraldehyde 3-phosphate GenomeNet: Glycerone phosphate (Dihydroxyacetone phosphate) GenomeNet: beta-D-Fructose 1,6-bisphosphate GenomeNet: beta-D-Fructose 6-phosphate GenomeNet: beta-D-Glucose 6-phosphate GenomeNet: D-Glucose ( Grape sugar; Dextrose ) GeneNet: ATP ( Adenosine 5'-triphosphate ) GeneNet: ADP ( Adenosine 5'-diphosphate ) GeneNet: ADP ( Adenosine 5'-diphosphate ) GeneNet: GTP ( Guanosine 5'-triphosphate ) GeneNet: GDP ( Guanosine 5'-diphosphate; Guanosine diphosphate ) GeneNet: ATP (Adenosine 5'-triphosphate; C10H16N5O13P3 ) GeneNet: NADH ( C21H29N7O14P2 ) GeneNet: NAD+ ( Nicotinamide adenine dinucleotide; C21H28N7O14P2 ) Overzicht Gluconeogenese

 

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