Subsystem: Glycolysis and Gluconeogenesis, including Archaeal enzymes

This subsystem's description is:

This Subsystem focuses on implementaion of glycolysis and glyconeogenesis in Archaea (the corresponding processes in Eubacteria are encoded in SS “Glycolysis and Gluconeogenesis”. This SS has been initiated by Ross Overbeek and is currently curated by Svetlana Gerdes.

Glycolysis (Embden-Meyerhof-Parnas pathway) in Archaea differs significantly from that in bacteria and eukaryotes. Just a few striking examples:
-- zero or very low ATP yields
-- many unusual glycolytic enzymes, including ADP-dependent gluco- and phosphofructo- kinases, non-orthologous PGMs, FBAs, non-phosphorylating GAP dehydrogenases, etc.
-- reduction of ferredoxin rather than NADH, etc

Notably, much less variation is observed in glyconeogenic enzymes. This probably reflects the independent evolution of catabolic branches in bacteria and archaea diverging from originally glyconeogenic EMP pathway (refs. 2, 5) . Since studies of archaeal glycolytic pathways have started only in early 1990s, a large number of open questions (including “missing” enzymes) remains. A diagram of archaeal EMP/glyconeogenesis pathway is posted on SEED Forum at: http://brucella.uchicago.edu/SubsystemForum/showthread.php?p=357#post357

Out of 10 enzymatic steps, which constitute classical EMP 7 are reversible and work in glyconeogenesis as well. However, glycolytic reactions catalyzed by the following enzymes are not reversible:
(i) 6-phosphofructokinase (EC 2.7.1.11),
(ii) Pyruvate kinase (EC 2.7.1.40),
(iii) some forms of glyceraldehyde 3-phosphate dehydrogenase (see below)
They are bypassed during glyconeogenesis via:
(i) Fructose-1,6-bisphosphatase (EC 3.1.3.11),
(ii) PEP synthase (EC 2.7.9.2) or/and Pyruvate,phosphate dikinase (EC 2.7.9.1),
(iii) NAD(P)-dependent glyceraldehyde 3-phosphate dehydrogenase
respectively or by utilizing other central metabolic pathways


References:

RossO: I highly recommend Verhees doctoral thesis -
1."Molecular characterization of glycolysis in Pyrococcus furiosus", for his discussions of what is going on in the Archaea. Most of it has been published since:

2. Verhees CH, Kengen SW, Tuininga JE, Schut GJ, Adams MW, De Vos WM, Van Der Oost J. 2003. The unique features of glycolytic pathways in Archaea. Biochem J. 375:231-46.

3. Ronimus RS, Morgan HW. 2003. Distribution and phylogenies of enzymes of the Embden-Meyerhof-Parnas pathway from archaea and hyperthermophilic bacteria support a gluconeogenic origin of metabolism. Archaea 1(3):199-221. Review.

4. T. Sato, H. Imanaka, N. Rashid, T. Fukui, H. Atomi, and T. Imanaka. 2004. Genetic Evidence Identifying the True Gluconeogenic Fructose-1,6-Bisphosphatase in Thermococcus kodakaraensis and Other Hyperthermophiles. J. Bact., 186: 5799–5807

5. Stec, B., Yang, H., Johnson, K. A., Chen, L. and Roberts, M. F. 2000. MJ0109 is an
enzyme that is both an inositol monophosphatase and the ‘missing’ archaeal
fructose-1,6-bisphosphatase. Nat. Struct. Biol. 7, 1046–1050

For more information, please check out the description and the additional notes tabs, below

DiagramFunctional RolesSubsystem SpreadsheetDescriptionAdditional Notes 

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This Subsystem focuses on implementaion of glycolysis and glyconeogenesis in Archaea (the corresponding processes in Eubacteria are encoded in SS “Glycolysis and Gluconeogenesis”. This SS has been initiated by Ross Overbeek and is currently curated by Svetlana Gerdes.

Glycolysis (Embden-Meyerhof-Parnas pathway) in Archaea differs significantly from that in bacteria and eukaryotes. Just a few striking examples:
-- zero or very low ATP yields
-- many unusual glycolytic enzymes, including ADP-dependent gluco- and phosphofructo- kinases, non-orthologous PGMs, FBAs, non-phosphorylating GAP dehydrogenases, etc.
-- reduction of ferredoxin rather than NADH, etc

Notably, much less variation is observed in glyconeogenic enzymes. This probably reflects the independent evolution of catabolic branches in bacteria and archaea diverging from originally glyconeogenic EMP pathway (refs. 2, 5) . Since studies of archaeal glycolytic pathways have started only in early 1990s, a large number of open questions (including “missing” enzymes) remains. A diagram of archaeal EMP/glyconeogenesis pathway is posted on SEED Forum at: http://brucella.uchicago.edu/SubsystemForum/showthread.php?p=357#post357

Out of 10 enzymatic steps, which constitute classical EMP 7 are reversible and work in glyconeogenesis as well. However, glycolytic reactions catalyzed by the following enzymes are not reversible:
(i) 6-phosphofructokinase (EC 2.7.1.11),
(ii) Pyruvate kinase (EC 2.7.1.40),
(iii) some forms of glyceraldehyde 3-phosphate dehydrogenase (see below)
They are bypassed during glyconeogenesis via:
(i) Fructose-1,6-bisphosphatase (EC 3.1.3.11),
(ii) PEP synthase (EC 2.7.9.2) or/and Pyruvate,phosphate dikinase (EC 2.7.9.1),
(iii) NAD(P)-dependent glyceraldehyde 3-phosphate dehydrogenase
respectively or by utilizing other central metabolic pathways


References:

RossO: I highly recommend Verhees doctoral thesis -
1."Molecular characterization of glycolysis in Pyrococcus furiosus", for his discussions of what is going on in the Archaea. Most of it has been published since:

2. Verhees CH, Kengen SW, Tuininga JE, Schut GJ, Adams MW, De Vos WM, Van Der Oost J. 2003. The unique features of glycolytic pathways in Archaea. Biochem J. 375:231-46.

3. Ronimus RS, Morgan HW. 2003. Distribution and phylogenies of enzymes of the Embden-Meyerhof-Parnas pathway from archaea and hyperthermophilic bacteria support a gluconeogenic origin of metabolism. Archaea 1(3):199-221. Review.

4. T. Sato, H. Imanaka, N. Rashid, T. Fukui, H. Atomi, and T. Imanaka. 2004. Genetic Evidence Identifying the True Gluconeogenic Fructose-1,6-Bisphosphatase in Thermococcus kodakaraensis and Other Hyperthermophiles. J. Bact., 186: 5799–5807

5. Stec, B., Yang, H., Johnson, K. A., Chen, L. and Roberts, M. F. 2000. MJ0109 is an
enzyme that is both an inositol monophosphatase and the ‘missing’ archaeal
fructose-1,6-bisphosphatase. Nat. Struct. Biol. 7, 1046–1050
Multi-positional encoding of variant codes was utilized here in order to capture (at least a fraction of!) endless variations of EMP and glyconeogenesis in different species of Archaea.

Variant code = -1:
(i) assigned to all eubacteria, since this SS is focused on Archaea (please see SS: Glycolysis and Gluconeogenesis for eubacteria)
(ii) assignd to Archaea, if the majority of enzymes are absent, no functional EPM/glyconeogenesis can be asserted, as it is the case in Nanoarchaeum equitans Kin4-M

A star(s) in a variant code indicates that one or more enzymes expected to be present in the genome based on functional context could not be identified (“missing genes”).

FIRST digit reflects the type of a sugar kinase catalyzing formation of glucose-6-P in an organism:

1 = an ATP-dependent hexo- or glucokinase(s) is present
3 = an ADP-dependent glucokinase is present
8 = different types of kinases (ADP - ATP- , or PPi-dependent) can be asserted in an organism
9 = no sugar kinase could be identified. Glucokinases are “missing” enzymes in several saccharolytic archaea, which lack a potential bypass - GDH channeling glucose into non-phosphorylating ED, and hence, are expected to have functional Glk, including: Archaeoglobus fulgidus, Methanococcus maripaludis. Their variant codes have a star.


SECOND digit reflects a type of 6-phosphofructokinase (Pfk) present:

1 = ATP-dependent Pfk is present (one or several types)
2 = PPi-dependent Pfk is present. ATP yield of glycolysis is higher in this case.
3 = an ADP-dependent Pfk is present
8 = different types of kinases (ADP - ATP- , or PPi-dependent) can be asserted
9 = no ortholog of known PFKs can be detected in a genome. In the majority of these organisms the presence of glucose 1-dehydrogenase (GDH, included in this SS) catalyzing the first step of alternative pathways of glucose catabolism indicates that archaeal Entner-Doudoroff and/or Pentose Phosphate pathways are used in place of glycolysis. This is the apparently the case in: Ferroplasma acidarmanus, Picrophilus torridus, Halobacterium sp. NRC-1, Haloarcula marismortui, and all sequenced species of Sulfolobus and Thermoplasma. The absence of both enzymes - Pfk and GDH in an organism is characteristic of autotrophs Methanopyrus kandleri and Methanothermobacter thermautotrophicus, unable to utilize hexoses and apparently lacking internal glycogen cycle (accumulating cyclic 2,3-Diphosphoglycerate instead). On the other hand, Pfk is expected to be present, but is not found (“missing” gene) in genomes of Pyrobaculum aerophilum and Archaeoglobus fulgidus


THIRD digit reflects the presence/absence of Fructose-bisphosphate aldolase, archaeal class I:

1 = FBA, archaeal class I can be asserted
9 = FBA is missing. Note, that Archaeal class I FBA is a divergent family, difficult to separate from other aldolases. Tried to pick only one paralog per genome (but Methanosarcinas apparently have 2 legitimate copies – at least by clustering) – see notes on enzymes


FOURTH digit reflects a type of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) present:

1 = a single universal GAPD(P)H apparently acts in both directions - in glycolysis AND glyconeogenesis
4 = two distinct enzymes: GAPDHs catalyze 1,3-bisP-glycerate → glyceraldehyde-3P conversion in glyconeogenesis, while GAPOR or/and G3PNPa catalyze irreversible oxidation of glyceraldehyde-P to glycerate-3P in the direction of glycolysis. ATP yield of glycolysis is zero in this case
9 = no GAPDH. Extremely rare – occurs only in species missing EMP/glyconeogenic pathway completely (e.g. Nanoarchaeum equitans Kin4-M)


To keep variant encoding as simple as possible, the following variations of EMP/glycolysis have NOT been reflected in variant codes, but should be kept in mind:

5. the presence/ absence of some form of Fructose-1,6-bisphosphatase (FBP), required for glyconeogenesis. Note: It is not clear, whether bifunctional FBP/myoinositol-1-phosphatase (COG0483) proposed for the role of FBP in archaea earlier (e.g. MJ0109, ref 4) does indeed function as FBP.
CONTRA: (i) the phenotypes of FBP knockouts generated in Thermococcus kodakaraensis (ref 3);
(ii) occurence profile: three other forms of FBP nicely cover phylogenetic space in Archaea.
PRO: (i) the presence of FBP activity in vitro in MJ0109 (ref 4),
(ii) MJ0109 (COG0483) clusters with pyruvate kinase, and in the Methanosarcinia COG0483 clusters with glyceraldehyde 3-phosphae dehydrogenase,
(iii) COG0483 homolog (peg.1400) seems to be the only likely FBP in Thermotoga maritima.

6. While several archaea contain orthologs of classical glucose-6P isomerase (Pgi), others posses one of the two archaeal enzymes (unrelated to bacterial Pgi on sequence level). The exceptions are - Methanopyrus kandleri AV19 and Methanothermobacter thermautotrophicus str. Delta H (see above)

7. Archaea have their own class I FBA, unrelated to bacterial FBA I on the sequence level, but with the same Shiff base mechanism. The majority of archaeal genomes sequenced to date contain at least one gene homolog. Clear FBA homolog are missing in the genomes of Pyrobaculum aerophilum, Ferroplasma acidarmanus, Thermoplasma acidophilum and Thermoplasma volcanium, Picrophilus torridus DSM 9790. In addition, in the following genomes none of the “aldolase of the DhnA family” homologs, albeit present, were annotated as FBA: Archaeoglobus fulgidus DSM 4304, Methanopyrus kandleri AV19, Methanothermobacter thermautotrophicus. These proteins appear to be phospho-2-dehydro-3-deoxyheptonate aldolases, rather then FBAs - based on (i) the strong clustering with other chorismate biosynthesis genes and on (ii) the absence of all other known types of phospho-2-dehydro-3-deoxyheptonate aldolase in these genomes. They are currently annotated in SEED as “Alternative step 1 of chorismate biosynthesis”


8. The presence/absence of Pyruvate kinase (PyK) acting in the direction of glycolysis. No clear orthologs of PyK could be asserted in the genomes of: Methanopyrus kandleri AV19 and Methanothermobacter thermautotrophicus, and Archaeoglobus fulgidus DSM 4304


A note of caution: in unfinished genomes any “9” in variant code should be taken with a grain of salt. The gene may be as well present – but could have been missed or fragmented beyond recognition by an ORF-calling program. A DNA BLAST against the genome of interest is recommended. The state of completeness for each genome can be assessed from the FIG Search page – look at the window “If You Need to Pick a Genome for Options Below”. For further details, highlight the genome of interest and press “statistics” button.