Distinct features of the Entner–Doudoroff pathway are that it:
Uses the unique enzymes 6-phosphogluconate dehydratase aldolase and 2-keto-deoxy-6-phosphogluconate (KDPG) aldolase and other common metabolic enzymes to other metabolic pathways to catabolize glucose to pyruvate.[1]
In the process of breaking down glucose, a net yield of 1 ATP is formed per every one glucose molecule processed, as well as 1
NADH and 1
NADPH. In comparison, glycolysis has a net yield of 2 ATP molecules and 2 NADH molecules per every one glucose molecule metabolized. This difference in energy production may be offset by the difference in protein amount needed per pathway.[5]
Archaeal variations
Archaea have variants of the Entner-Doudoroff Pathway. These variants are called the semiphosphorylative ED (spED) and the nonphosphorylative ED (npED):[6]
In spED, the difference is where
phosphorylation occurs. In the standard ED, phosphorylation occurs at the first step from glucose to G-6-P. In spED, the glucose is first oxidized to
gluconate via a glucose dehydrogenase. Next, gluconate dehydratase converts gluconate into 2-keto-3-deoxy-gluconate (KDG). The next step is where phosphorylation occurs as KDG kinase converts KDG into KDPG. KDPG is then cleaved into glyceraldehyde 3-phosphate (GAP) and pyruvate via KDPG aldolase and follows the same EMP pathway as the standard ED. This pathway produces the same amount of ATP as the standard ED.[6]
In npED, there is no phosphorylation at all. The pathway is the same as spED but instead of phosphorylation occurring at KDG, KDG is instead cleaved GA and pyruvate via KDG aldolase. From here, GA is oxidized via GA dehydrogenase into glycerate. The glycerate is phosphorylated by glycerate kinase into 2PG. 2PG then follows the same pathway as ED and is converted into pyruvate via ENO and PK. In this pathway though, there is no ATP produced.[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
This section needs expansion with: the further known species that use the ED or its variants, based on the reviews provided, and other modern secondary sources. You can help by
adding to it. (August 2015)
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]
Phaeodactylum tricornutum diatom model species presents functional phosphogluconate dehydratase and dehoxyphosphogluconate aldolase genes in its genome [14]
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
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 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
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+
References
^
abcConway,T. (1992) "The Entner–Doudorodd pathway: history, physiology and molecular biology" Microbiology of Reviews103(19; May), pp. 1–28, DOI , see
[1]
^
abcChen, 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.
^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,
ISBN0387241450,
[3], accessed 3 August 2015.
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
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Ahmed, H.; B. Tjaden; R. Hensel & B. Siebers (2004) "Embden–Meyerhof–Parnas and Entner–Doudoroff pathways in Thermoproteus tenax: metabolic parallelism or specific adaptation?," Biochem. Soc. Trans.32(2; April 1), pp. 303–304, DOI 10.1042/bst0320303, see
[6], accessed 3 August 2015.
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