Comparative Analysis of EMP, HMP, and ED Pathways in Glucose Metabolism: Biochemical Features, Steps, Modifications, and Significance in Prokaryotes and Eukaryotes

FeaturesEMPHMPED
SubstrateGlucose 
In modified EMP,
Halophilic archae like Haloarcula vallismortis can also transport fructose via active transport converting it to Fructose-1,6diphosphate via through fructose-1phosphate by ketohexokinase and 1phosphofructokinase. Hyperthermophilic archae like Pyrococcus furiosus can ferment Laminarin not glucose and can hydrolyse it outside cell into oligosaccharides and transport into cell for glycolysis.
Glucose-6-phosphateGlucose mostly,
Gluconate (when
gluconate and
other acid sugars
are present eg: In
E. coli, Gluconate
is available in the
intestinal milieu,
can be as an
energy source.
ATP Yield2 ATP per glucose molecule.
No direct use or production of
ATP
One ATP per glucose molecule
Final product2 pyruvic acids. In case of hyperthermophilic archae like Pyrococcus furiosus, pyruvate is reduced as an electron acceptor to alanine.Produces
Phosphoglyceraldehyde , fructose-6-phosphate and CO2
One pyruvic acid and one
Glyceraldehyde 3phosphate
Nature of pathwayCatabolicAnabolic in natureCatabolic
Organisms using pathwaysAlmost a universal pathway occurring in both eukaryotes and prokaryotes in cytoplasm. Essential for brain which is highly dependent on glucose for energy.Both eukaryotes and prokaryotes in cytoplasm, most steps taking place in plastids in plants. In human, tissues like liver, adipose tissue, mammary gland, testes, RBCs where active biosynthesis of steroids and fatty acids is high.Prokaryotes in cytoplasm. Occurring in microorganisms that lack
Phosphofructokina se-1 and aerobes which depend largely on TCA for ATP generation
utilize this
pathway. E.g. Pseudomonads
Phases of pathwayPreparatory and pay-off phaseOxidative and non-oxidative phaseNo such distinction of phases in ED pathway
Phosphoryl group donorATP and so ATP dependent kinase is used.
In case of modified
EMP in Pyrococcus furiosus, ADP act as phosphoryl donor as ADP is more stable in high temperature so ADP dependent kinase
is used
No ATP directly usedATP and so ATP dependent kinase is used for phosphorylation.
SignificanceEnergy generation in aerobic condition (Net
ATP: 8 moles)
Produces pentoses for nucleic acid synthesis and many nucleotides and NADPH for biosynthesis of fatty acids and steroids, phagocytosis, antioxidation.  Energy generation in the form of ATP though lower than EMP and has higher thermodynamic driving force. Also generated 1
NADHP.
Reducing equivalent generatedNADH+ H+NADPHProduces NADH and NADPH both

Introduction to Glucose Metabolic Pathways:

 EMP, HMP, and the ED pathways, all three pathways, are the best-characterized pathways for sugar catabolism in bacteria and are crucial for their physiology and nutrition.

  • All three pathways take place in cytoplasm. EMP takes place in cytoplasm in two phases: preparatory and pay-off phase. The HMP occurs in the cytosol two biochemical branches: An oxidative and a non-oxidative branch. ED pathway also occurs in cytoplasm. In some pseudomonads, ED pathway can occur in periplasm when glucose concentration is high.
  • All three pathways have modified versions which are used by organisms based on genetic capabilities and environmental conditions that they need to survive.
  • All three pathways are highly regulated and have key enzymes that govern the cycles. In EMP pathway, the key enzymes are glucokinase, phosphofructokinase and pyruvate kinase Glucose 6 phosphate dehydrogenase is the primary regulatory enzyme in the HMP pathway. Glucose Dehydrogenase, Gluconate Dehydratase, and 2-Keto-3-Deoxy-6-Phosphogluconate Aldolase are the main enzymes in the ED route.

ED and EMP modifications are seen in Archae and both modified pathways use ferrodoxin oxidoreductase (Glyceraldehyde-3-phosphate: ferrodoxin oxidoreductase in EMP pathway and Glucose: ferrodoxin oxidoreductase in ED pathway) which have relatively lower reduction potential that other reducing equivalents like NAD+) ED and EMP pathways are widespread in prokaryotes. The overall designs of the ED and EMP pathways are somewhat similar: Six-carbon sugars are primed by phosphorylation and subsequently broken down into two 3-carbon intermediates by the enzyme aldolase. Both the ED and EMP pathways create pruvate. The cytoplasmic HMP shunt occurs concurrently with the glycolysis process. A 6-carbon sugar called glucose may enter the glycolytic pathway or the alternative HMP shunt, depending on the particular needs of the cell at that time.

The hexose monophosphate pathway of glucose metabolism comprises a rather complicated series of reactions which can be carried out by many organisms that metabolize glucose via the EMP or ED pathway. The transformation of glucose into glucose-6-phosphate mirrors the initial step of the EMP pathway. However, from that point onward, the HMP pathway diverges. Interestingly, not all organisms that metabolize sugars adhere to the traditional EMP route. Prokaryotes, in particular, exhibit a wide range of glycolytic strategies tailored to their environmental energy conditions. Anaerobic microbes with limited energy resources typically favor the EMP pathway due to its higher ATP output. In contrast, facultative anaerobes and aerobic bacteria often utilize the ED pathway or the HMP pathway, the latter being more associated with biosynthetic functions than energy production.

Glycolysis sets the stage by supplying the initial six-carbon glucose molecule needed to fuel the pentose phosphate pathway. This pathway is flexible, drawing on any available glucose-6-phosphate, regardless of its origin—be it glycolysis or another metabolic route. When comparing pathways with lactate as the end product, both routes converge on an identical net reaction. These metabolic routes intersect at the stage known as lower glycolysis, beginning with glyceraldehyde 3-phosphate (G3P) and culminating in pyruvate formation. Chemically, the ED pathway can be seen as a streamlined variant of the EMP route, with its upper phase reconfiguring the six-carbon framework before proceeding through the shared lower glycolysis steps.

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