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 deficiëntie
   
   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:

	Introduction in gluconeogenesis
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