Entner–Doudoroff pathway

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Diagram of the Entner-Doudoroff pathway (KDPG: 2-keto-3-deoxy-6-phosphogluconate) Entner-Doudoroff pathway.svg
Diagram of the Entner–Doudoroff pathway (KDPG: 2-keto-3-deoxy-6-phosphogluconate)

The Entner–Doudoroff pathway (ED Pathway) is a metabolic pathway that is most notable in Gram-negative bacteria, certain Gram-positive bacteria and archaea. [1] Glucose is the substrate in the ED pathway and through a series of enzyme assisted chemical reactions it is catabolized into pyruvate. Entner and Doudoroff (1952) and MacGee and Doudoroff (1954) first reported the ED pathway in the bacterium Pseudomonas saccharophila . [2] While originally thought to be just an alternative to glycolysis (EMP) and the pentose phosphate pathway (PPP), some studies now suggest that the original role of the EMP may have originally been about anabolism and repurposed over time to catabolism, meaning the ED pathway may be the older pathway. [3] Recent studies have also shown the prevalence of the ED pathway may be more widespread than first predicted with evidence supporting the presence of the pathway in cyanobacteria, ferns, algae, mosses, and plants. [4] Specifically, there is direct evidence that Hordeum vulgare uses the Entner–Doudoroff pathway. [4]

Contents

Distinct features of the Entner–Doudoroff pathway are that it:

Archaeal variations

Archaea have variants of the Entner-Doudoroff Pathway. These variants are called the semiphosphorylative ED (spED) and the nonphosphorylative ED (npED): [6]

Some archaea such as Crenacraeota Sul. solfacaricus and Tpt. tenax have what is called branched ED. In branched ED, the organism have both spED and npED that are both operative and work in parallel.

Organisms that use the Entner–Doudoroff pathway

There are several bacteria that use the Entner–Doudoroff pathway for metabolism of glucose and are unable to catabolize via glycolysis (e.g., therefore lacking essential glycolytic enzymes such as phosphofructokinase as seen in Pseudomonas). [1] Genera in which the pathway is prominent include Gram-negative,[ citation needed ] as listed below, Gram-positive bacteria such as Enterococcus faecalis, [7] [ full citation needed ][ page needed ][ better source needed ] as well as several in the Archaea, the second distinct branch of the prokaryotes (and the "third domain of life", after the prokaryotic Eubacteria and the eukaryotes). [6] Due to the low energy yield of the ED pathway, anaerobic bacteria seem to mainly use glycolysis while aerobic and facultative anaerobes are more likely to have the ED pathway. This is thought to be due to the fact that aerobic and facultative anaerobes have other non-glycolytic pathways for creating ATP such as oxidative phosphorylation. Thus, the ED pathway is favored due to the lesser amounts of proteins required. While anaerobic bacteria must rely on the glycolysis pathway to create a greater percentage of their required ATP thus its 2 ATP production is more favored over the ED pathway's 1 ATP production. [5]

Examples of bacteria using the pathway are:

To date there is evidence of Eukaryotes using the pathway, suggesting it may be more widespread than previously thought:

The Entner–Doudoroff pathway is present in many species of Archaea (caveat, see following), whose metabolisms "resemble... in [their] complexity those of Bacteria and lower Eukarya", and often include both this pathway and the Embden-Meyerhof-Parnas pathway of glycolysis, except most often as unique, modified variants. [6]

Catalyzing enzymes

Conversion of glucose to glucose-6-phosphate

The first step in ED is phosphorylation of glucose by a family of enzymes called hexokinases to form glucose 6-phosphate (G6P). This reaction consumes ATP, but it acts to keep the glucose concentration low, promoting continuous transport of glucose into the cell through the plasma membrane transporters. In addition, it blocks the glucose from leaking out – the cell lacks transporters for G6P, and free diffusion out of the cell is prevented due to the charged nature of G6P. Glucose may alternatively be formed from the phosphorolysis or hydrolysis of intracellular starch or glycogen.

In animals, an isozyme of hexokinase called glucokinase is also used in the liver, which has a much lower affinity for glucose (Km in the vicinity of normal glycemia), and differs in regulatory properties. The different substrate affinity and alternate regulation of this enzyme are a reflection of the role of the liver in maintaining blood sugar levels.

Cofactors: Mg2+

Conversion of glucose-6-phosphate to 6-phosphogluconolactone

The G6P is then converted to 6-phosphogluconolactone in the presence of enzyme glucose-6-phosphate dehydrogenase (an oxido-reductase) with the presence of co-enzyme nicotinamide adenine dinucleotide phosphate (NADP+). which will be reduced to nicotinamide adenine dinucleotide phosphate hydrogen along with a free hydrogen atom H+.

Conversion of 6-phosphogluconolactone to 6-phosphogluconic acid

The 6PGL is converted into 6-phosphogluconic acid in the presence of enzyme hydrolase.

Conversion of 6-phosphogluconic acid to 2-keto-3-deoxy-6-phosphogluconate

The 6-phosphogluconic acid is converted to 2-keto-3-deoxy-6-phosphogluconate (KDPG) in the presence of enzyme 6-phosphogluconate dehydratase; in the process, a water molecule is released to the surroundings.

Conversion of 2-keto-3-deoxy-6-phosphogluconate to pyruvate and glyceraldehyde-3-phosphate

The KDPG is then converted into pyruvate and glyceraldehyde-3-phosphate in the presence of enzyme KDPG aldolase. For the pyruvate, the ED pathway ends here, and the pyruvate then goes into further metabolic pathways (TCA cycle, ETC cycle, etc).

The other product (glyceraldehyde-3-phosphate) is further converted by entering into the glycolysis pathway, via which it, too, gets converted into pyruvate for further metabolism.

Conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate

The G3P is converted to 1,3-bisphosphoglycerate in the presence of enzyme glyceraldehyde-3-phosphate dehydrogenase (an oxido-reductase).

The aldehyde groups of the triose sugars are oxidised, and inorganic phosphate is added to them, forming 1,3-bisphosphoglycerate.

The hydrogen is used to reduce two molecules of NAD+, a hydrogen carrier, to give NADH + H+ for each triose.

Hydrogen atom balance and charge balance are both maintained because the phosphate (Pi) group actually exists in the form of a hydrogen phosphate anion (HPO42−), which dissociates to contribute the extra H+ ion and gives a net charge of -3 on both sides.

Conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate

This step is the enzymatic transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP by phosphoglycerate kinase, forming ATP and 3-phosphoglycerate.

Conversion of 3-phosphoglycerate to 2-phosphoglycerate

Phosphoglycerate mutase isomerises 3-phosphoglycerate into 2-phosphoglycerate.

Conversion of 2-phosphoglycerate to phosphoenolpyruvate

Enolase next converts 2-phosphoglycerate to phosphoenolpyruvate. This reaction is an elimination reaction involving an E1cB mechanism.

Cofactors: 2 Mg2+: one "conformational" ion to coordinate with the carboxylate group of the substrate, and one "catalytic" ion that participates in the dehydration

Conversion of phosphoenol pyruvate to pyruvate

A final substrate-level phosphorylation now forms a molecule of pyruvate and a molecule of ATP by means of the enzyme pyruvate kinase. This serves as an additional regulatory step, similar to the phosphoglycerate kinase step.

Cofactors: Mg2+

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References

  1. 1 2 3 Conway,T. (1992) "The Entner–Doudorodd pathway: history, physiology and molecular biology" Microbiology of Reviews103(19; May), pp. 1–28, DOI , see
  2. Kersters, K.; De Ley, J. (December 1968). "The occurrence of the Entner-Doudoroff pathway in bacteria". Antonie van Leeuwenhoek. 34 (1): 393–408. doi:10.1007/BF02046462. ISSN   0003-6072. PMID   5304016. S2CID   6151383.
  3. Romano, A. H.; Conway, T. (1996-07-01). "Evolution of carbohydrate metabolic pathways". Research in Microbiology. 147 (6): 448–455. doi: 10.1016/0923-2508(96)83998-2 . ISSN   0923-2508. PMID   9084754.
  4. 1 2 3 Chen, Xi, et al. "The Entner–Doudoroff pathway is an overlooked glycolytic route in cyanobacteria and plants." Proceedings of the National Academy of Sciences (2016): 201521916.
  5. 1 2 Flamholz, A.; Noor, E.; Bar-Even, A.; Liebermeister, W.; Milo, R. (2013-04-29). "Glycolytic strategy as a tradeoff between energy yield and protein cost". Proceedings of the National Academy of Sciences. 110 (24): 10039–10044. Bibcode:2013PNAS..11010039F. doi: 10.1073/pnas.1215283110 . ISSN   0027-8424. PMC   3683749 . PMID   23630264.
  6. 1 2 3 4 5 6 7 Bräsen C.; D. Esser; B. Rauch & B. Siebers (2014) "Carbohydrate metabolism in Archaea: current insights into unusual enzymes and pathways and their regulation," Microbiol. Mol. Biol. Rev.78(1; March), pp. 89–175, DOI 10.1128/MMBR.00041-13, see "Carbohydrate Metabolism in Archaea: Current Insights into Unusual Enzymes and Pathways and Their Regulation". Archived from the original on 2015-11-22. Retrieved 2015-08-04. or , accessed 3 August 2015.
  7. Willey; Sherwood; Woolverton. Prescott's Principles of Microbiology.[ full citation needed ][ page needed ]
  8. 1 2 Peekhaus N, Conway T (1998). "What's for dinner?: Entner–Doudoroff metabolism in Escherichia coli". J Bacteriol. 180 (14): 3495–502. doi:10.1128/JB.180.14.3495-3502.1998. PMC   107313 . PMID   9657988.
  9. Michael P. Stephenson; Frank A. Jackson; Edwin A. Dawes (1978). "Further Observations on Carbohydrate Metabolism and its Regulation in Azotobacter beijerinckii". Journal of General Microbiology. 109 (1): 89–96. doi: 10.1099/00221287-109-1-89 .
  10. Kuykendall, L. David; John M. Young; Esperanza Martínez-Romero; Allen Kerr & Hiroyuka Sawada (2006) Genus I. Rhizobium Frank 1889, 389AL [Order VI. Rhizobiales ord. nov., Family I Rhizobiaceae Conn 1938, 321AL (L. David Kuykendall, Ed.)], pp. 324–339, in Bergey's Manual® of Systematic Bacteriology, Vol. 2 The Proteobacteria, Part 3 The Alpha-, Beta-, Delta-, and Epsilonproteobacteria, (Don J. Brenner, Noel R. Krieg, James T. Staley, Vol. Eds., George M. Garrity, Ed.-in-Chief), New York, NY, USA: Springer Science & Business, ISBN   0387241450, , accessed 3 August 2015.
  11. Arthur LO, Nakamura LK, Julian G, Bulla LA (1975). "Carbohydrate catabolism of selected strains in the genus Agrobacterium". Appl Microbiol. 30 (5): 731–7. doi:10.1128/AEM.30.5.731-737.1975. PMC   187263 . PMID   128316.
  12. Goddard J. L.; J.R. Sokatch (1964). "2-Ketogluconate fermentation by Streptococcus faecalis". J. Bacteriol. 87 (4): 844–851. doi:10.1128/JB.87.4.844-851.1964. PMC   277103 . PMID   14137623.
  13. Lu, G. T.; J.R. Xie; L. Chen; J. R. Hu; S. Q. An; H. Z. Su; et al. (2009). "Glyceraldehyde-3-phosphate dehydrogenase of Xanthomonas campestris pv. campestris is required for extracellular polysaccharide production and full virulence". Microbiology. 155 (5): 1602–1612. doi: 10.1099/mic.0.023762-0 . PMID   19372163.
  14. Fabris M., et al., "The metabolic blueprint of Phaeodactylum tricornutum reveals a eukaryotic Entner–Doudoroff glycolytic pathway", The Plant Journal (2012) 70, 1004–1014

Further reading