S.Ramya I M.Sc Microbiology

 Fructose Bisphosphate Aldolase Pathway  Entner-Doudoroff Pathway  Phosphoketolase Pathway

 Warburg and Christian provided the first evidence for the existence of an alternative pathway for the utilization of hexose sugars.  They described the oxidation of glucose-6- phosphate to 6-phosphogluconate (6-P-G) via G-6-P dehydrogenase.  They also described the decarboxylation of 6-P-G to form a pentose sugar.

 For a long time, relatively little attention was paid to the real significance of this alternative pathway because Meyerhof and others strongly asserted that the FBP aldolase (EMP) pathway was the main route of glucose catabolism.  Subsequently, ribulose-6-phosphate was shown to be the first product formed and was converted to ribose-5-phosphate via an isomerase reaction.  This series of reactions is common to several alternate pathways of carbohydrate metabolism

A LTERNATIVE P ATHWAYS Alternative pathways found in different bacteria: Fructose Bisphosphate Aldolase Pathway Found in almost all organisms Entner-Doudoroff pathway Found in Pseudomonas and related genera Phosphoketolase pathway Found in Bifidobacterium and Leuconostoc

 This is also called as Embden-Meyerhof-Parnas pathway or Glycolysis. Important reactions:  Phosphorylation of glucose and fructose-6- phosphate by ATP.  Cleavage of fructose-1,6-bisphosphate to trioses by a specific aldolase.  Structural rearrangements.  Oxidation-reduction and Pi assimilation

1. Phosphorylase. Degradation of glycogen or starch to G-1-P 2. Phosphoglucomutase. Isomerization of G-1- P to G-6-P 3. Hexokinase. Phosphorylation of glucose to G-6-P, using ATP Hexokinase also phosphorylates fructose to F-6-P using ATP

4. Phosphoglucoisomerase (pgi). Isomerization of G-6-P to F-6-P. 5. Phosphofructokinase (pfkA). Phosphorylation of F-6-P to FBP using ATP. 6. Fructose bisphosphate (FBP) aldolase (fbaA). Cleaves FBP to GA-3-P and dihydroxyacetone phosphate. 7. Triose phosphate isomerase (tpi ). Interconverts GA-3-P and dihydroxyacetone-P.

8. Glyceraldehyde-3-phosphate dehydrogenase (gap). Oxidizes GA-3-P to 1,3-diphosphoglycerate using NAD+(nicotinamide adenine dinucleotide) and inorganic phosphate (Pi) to form NADP + H+. 9. Phosphoglycerokinase (pgk) Generates ATP from ADP. 10. Phosphoglyceromutase (pgm). Uses 2,3- diphosphoglycerate to convert 3- phosphoglycerate to 2-phosphoglycerate.

11. Enolase (eno). Enolization of 2-phosphoglycerate forms high-energy phosphate bond (∼P; encircled P) in phosphoenolpyruvate (PEP). 12. Pyruvate kinase (pykA; pykF). Generates ATP from ADP. 13. Lactate dehydrogenase. Reduces pyruvate to lactate using NADP + H+.

14. Pyruvate carboxylase. Converts pyruvate to oxaloacetic acid (OAA) via carbon dioxide (CO2) fixation using ATP. 15. PEP carboxykinase. Forms phosphoenolpyruvate from OAA using GTP. 16. Fructose-1,6-bisphosphatase. Removes Pi from F-1,6-bisP to form F-6-P.

17. Glucose-6-phosphatase. Removes Pi from G-6-P to form glucose. 18. ATP-glucose pyrophosphorylase. Forms ADP-glucose from G-1-P and ATP. 19. Glycogen synthase. Adds α-1,4-glycan to ADP-glucose to form glycogen or starch

20. Glycerophosphate dehydrogenase. Reduces dihydroxyacetone-P to glycerol-3-P. 21. Phosphatase. Removes Pi from glycerol-3-P to form glycerol. 22. Glycerol kinase. Phosphorylates glycerol using ATP.

F RUCTOSE BISPHOSPHATE ALDOLASE PATHWAY

 The Entner–Doudoroff pathway branches from the Ketogluconate pathway of hexose oxidation.  It consist of two enzymes: 6- phosphogluconate dehydratase and 2-keto-3- deoxy-6-phosphogluconate aldolase.  Final product is ethanol.

 glucose-6-phosphate dehydrogenase (zwf, for zwischenferment) oxidizes glucose-6-phosphate to 6-phosphogluconolactone.  The lactone is dehydrated to 6-phosphogluconate via lactonase.  6-phosphogluconate is dehydrated by 6- phosphogluconate dehydratase (edd) to yield 2- keto-3-deoxy-6-phosphogluconate (KDPG).

 The enzyme 2-keto-3-deoxy-6-phosphogluconate aldolase cleaves 2-keto-3-deoxy-6- phosphogluconate to form pyruvate and GA-3-P (glyceraldehyde-3-phosphate).  Pyruvate decarboxylase action yields ethanol and carbon dioxide.  The GA-3-P is metabolized via the triose phosphate portion of the EMP pathway to yield ethanol and carbon dioxide.  The net yield in the Entner-Doudoroff pathway is 2 ethanol + 2 CO2.

E NTNER -D OUDOROFF P ATHWAY

 One major fermentation pathway involves the conversion of ribose-5-phosphate to xylulose-5-phosphate(X-5-P).  The X-5-P is then cleaved to form a C3 compound (glyceraldehyde-3-phosphate) and C2 compound (acetyl phosphate) by the action of the phosphoketolase enzyme.

P HOSPHOKETOLASE P ATHWAY