TABLE 3

Overview of enzymes involved in gluconeogenesis in Archaea, Bacteria, and Eukarya

EnzymeEC no.AbbreviationReactionProtein superfamily(ies) (according to the SCOP database)Protein family(ies)Distribution
Phosphoenolpyruvate carboxykinase4.1.1.32 (GTP), 4.1.1.49 (ATP)PCKOxaloacetate + GTP ⇆ phosphoenolpyruvate + CO2 + GDP (ADP)PEP carboxykinase N-terminal domain superfamily; PEP carboxykinase C-terminal domain superfamilyPEP carboxykinase N-terminal domain family, PEP carboxykinase C-terminal domain familyEukarya, Bacteria, Euryarchaeota, Crenarchaeota
Pyruvate:phosphate dikinase2.7.9.1PPDKPyruvate + ATP + Pi ⇆ phosphoenolpyruvate + AMP + PPiGlutathione synthetase ATP binding domain-like superfamily (N-terminal domain) (ATP grasp fold), phosphohistidine domain superfamily (central domain), phosphoenolpyruvate/pyruvate domain superfamily (C-terminal domain) (TIM barrel fold)Pyruvate:phosphate dikinase N-terminal, central, and C-terminal domain families, respectively (also known as the PEP-utilizing enzyme family)Eukarya, Bacteria, Archaea
Phosphoenolpyruvate synthase (pyruvate, water dikinase)2.7.9.2PEPSPyruvate + ATP + H2O ⇆ phosphoenolpyruvate + AMP + PiFrom sequence comparisons, domain organization likely similar to that of the glutathione synthetase ATP-binding domain-like superfamily (N-terminal domain) (ATP grasp fold); phosphohistidine domain superfamily (central domain); phosphoenolpyruvate-pyruvate domain superfamily (C-terminal domain) (TIM barrel fold)Pyruvate:phosphate dikinase N-terminal, central, and C-terminal domain families, respectively (also known as the PEP-utilizing enzyme family)Eukarya, Bacteria, Archaea
Enolase4.2.1.11ENOPhosphoenolpyruvate + H2O ⇆ 2-phosphoglycerateEnolase-like, N- and C-terminal domain superfamilyEnolase-like, N- and C-terminal domain-like familyEukarya, Bacteria, Archaea
2,3-Bisphosphoglycerate-independent phosphoglycerate mutase5.4.2.1iPGAM2-Phosphoglycerate ⇆ 3-phosphoglycerateAlkaline phosphatase superfamily, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase; substrate binding domain superfamily2,3-Bisphosphoglycerate-independent phosphoglycerate mutase, catalytic domain family; 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, substrate binding domain familyPlants, nematodes, Bacteria, Archaea
2,3-Bisphosphoglycerate-dependent phosphoglycerate mutase5.4.2.1dPGAM2-Phosphoglycerate ⇆ 3-phosphoglyceratePhosphoglycerate mutase-like superfamilyCofactor-dependent phosphoglycerate mutase familyVertebrates, yeasts, Bacteria, mainly thermoacidophilic Archaea and Methanosarcina spp.
Phosphoglycerate kinase2.7.3.2PGK3-Phosphoglycerate + ATP ⇆ 1,3-bisphosphoglycerate + ADPPhosphoglycerate kinase superfamilyPhosphoglycerate kinase familyEukarya, Bacteria, Archaea
Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)1.2.1.13 (NADP+), 1.2.1.12 (NAD+)GAPDH1,3-Bisphosphoglycerate + NAD(P)H + H+ ⇆ glyceraldehyde 3-phosphate + NAD(P)+ + PiN-terminal domain NAD(P) binding Rossman fold-like domain superfamily; C-terminal glyceraldehyde 3-phosphate dehydrogenase-like C-terminal domain superfamilyGAPDH N- and C-terminal domain families, respectivelyEukarya, Bacteria, Archaea
Triosephosphate isomerase5.3.1.1TIMGlyceraldehyde 3-phosphate ⇆ dihydroxyacetone phosphateTriosephosphate isomerase superfamily [(βα)8 barrel fold]Triosephosphate isomerase familyEukarya, Bacteria, Archaea
Fructose-1,6-bisphosphatase3.1.3.11FBPaseFructose 1,6-bisphosphate → fructose 6-phosphate + PiCarbohydrate phosphatase superfamilyInositol monophosphatase/fructose-1,6-bisphosphatase-like family (classes I and IV); GlpX-like bacterial fructose-1,6-bisphosphatase family (class II)Type I, Eukarya, Bacteria, and a few haloarchaea and methanogens; type II, Bacteria and a few methanogens; type III, Bacteria; type IV, Euryarchaeota, Crenarchaeota, and a few Bacteria (Thermotoga)
Fructose-1,6-bisphosphate aldolase class II4.1.2.13FBPA IIDihydroxyacetone phosphate + glyceraldehyde 3-phosphate ⇆ fructose 1,6-bisphosphateAldolase superfamily [(βα)8 barrel fold]Class II FBP aldolase familyA few halophilic Euryarchaeota, Bacteria, fungi
Archaeal-type class I fructose-1,6-bisphosphate aldolase4.1.2.13FBPA IADihydroxyacetone phosphate + glyceraldehyde 3-phosphate ⇆ fructose 1,6-bisphosphateAldolase superfamily [(βα)8 barrel fold]Class I aldolase familyArchaea, Bacteria
Fructose-1,6-bisphosphate aldolase class I4.1.2.13FBPA IDihydroxyacetone phosphate + glyceraldehyde 3-phosphate ⇆ fructose 1,6-bisphosphateAldolase superfamily [(βα)8 barrel fold]Class I aldolase familyEukarya
PPi-dependent phosphofructokinase2.7.1.90PPi-PFKFructose 1,6-bisphosphate + Pi ⇆ glucose 6-phosphate + PPiPhosphofructokinase superfamilyPhosphofructokinase family (known as PFK-A), forming a distinct subfamilyCrenarchaeota (Thermoproteus tenax), some Bacteria, Eukarya (protists, plants)
Fructose-1,6-bisphosphate aldolase/phosphatase (type V fructose-1,6-bisphosphatase)3.1.3.11FBPA/aseDihydroxyacetone phosphate + glyceraldehyde 3-phosphate → fructose 6-phosphate + PiSulfolobus fructose-1,6-bisphosphatase-like protein superfamily (SCOP database) (similarity to the ferredoxin fold in their N-terminal part and to bacterial S-adenosylmethionine decarboxylase in their C-terminal part)Sulfolobus fructose-1,6-bisphosphatase-like protein superfamily (SCOP database)Archaea, deeply branching Bacteria
Cupin-type phosphoglucose isomerase5.3.1.9cPGIFructose 6-phosphate ⇆ glucose 6-phosphateCupin superfamilycPGI familyAnaerobic Euryarchaeota (including Methanosarcina mazei), some Bacteria (Ensifer meliloti, Salmonella Typhimurium, horizontal gene transfer)
Phosphoglucose isomerase/phosphomannose isomerase5.3.1.9/5.3.1.8PGI/PMIFructose 6-phosphate ⇆ glucose 6-phosphate/mannose 6-phosphatePGI superfamily (SIS domain superfamily)PGI/PMI familyCrenarchaeota, Euryarchaeota (Thermoplasma)
Phosphoglucose isomerase5.3.1.9PGIFructose 6-phosphate ⇆ glucose 6-phosphatePGI superfamily (SIS domain superfamily)PGI familyEukarya, Bacteria, halophilic Euryarchaeota, methanogenic Euryarchaeota (Methanococcus)