Fructose-bisphosphate aldolase

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Fructose-bisphosphate aldolase
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Fructose-bisphosphate aldolase class-I
SCOP2
1ald / SCOPe / SUPFAM
CDDcd00344
Available protein structures:
Pfam  structures / ECOD  
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Fructose-bisphosphate aldolase class-II
SCOP2
1dos / SCOPe / SUPFAM
CDDcd00453
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Fructose-bisphosphate aldolase (

sedoheptulose 1,7-bisphosphate. Gluconeogenesis and the Calvin cycle, which are anabolic pathways, use the reverse reaction. Glycolysis, a catabolic pathway
, uses the forward reaction. Aldolase is divided into two classes by mechanism.

The word aldolase also refers, more generally, to an enzyme that performs an aldol reaction (creating an aldol) or its reverse (cleaving an aldol), such as Sialic acid aldolase, which forms sialic acid. See the list of aldolases.

Mechanism and structure

Class I proteins form a

N-acetyl galactosamine operon protein, agaY, which are tagatose-bisphosphate aldolase, are homologs of class II fructose-bisphosphate aldolase. Two histidine residues in the first half of the sequence of these homologs have been shown to be involved in binding zinc.[1]

The

sequence identity
.

With few exceptions only class I proteins have been found in

endosymbiosis, in addition to the usual cytosolic aldolase. A bifunctional fructose-bisphosphate aldolase/phosphatase, with class I mechanism, has been found widely in archaea and in some bacteria.[4]
The active site of this archaeal aldolase is also in a TIM barrel.

In gluconeogenesis and glycolysis

Gluconeogenesis and glycolysis share a series of six reversible reactions. In gluconeogenesis glyceraldehyde-3-phosphate is reduced to fructose 1,6-bisphosphate with aldolase. In glycolysis fructose 1,6-bisphosphate is made into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate through the use of aldolase. The aldolase used in gluconeogenesis and glycolysis is a cytoplasmic protein.

Three forms of class I protein are found in vertebrates.

substrate.[6] Archaeal fructose-bisphosphate aldolase/phosphatase is presumably involved in gluconeogenesis because its product is fructose 6-phosphate.[7]

In the Calvin cycle

The

sedoheptulose 1,7-bisphosphate from DHAP and erythrose 4-phosphate. The chief products of the Calvin cycle are triose phosphate (TP), which is a mixture of DHAP and G3P, and fructose 6-phosphate. Both are also needed to regenerate RuBP
. The aldolase used by plants and algae in the Calvin cycle is usually a plastid-targeted protein encoded by a nuclear gene.

Reactions

Aldolase catalyzes

fructose 1,6-bisphosphate ⇌ DHAP + G3P

and also

sedoheptulose 1,7-bisphosphate ⇌ DHAP + erythrose 4-phosphate
fructose 1-phosphate ⇌ DHAP + glyceraldehyde

Aldolase is used in the reversible trunk of gluconeogenesis/glycolysis

2(
PEP
+ NADH + H+ + ATP + H2O) ⇌ fructose 1,6-bisphosphate + 2(NAD+ + ADP + Pi)

Aldolase is also used in the part of the Calvin cycle shared with gluconeogenesis, with the irreversible phosphate hydrolysis at the end catalyzed by fructose 1,6-bisphosphatase

2(
3-PG
+ NADPH + H+ + ATP + H2O) ⇌ fructose 1,6-bisphosphate + 2(NADP+ + ADP + Pi)
fructose 1,6-bisphosphate + H2O → fructose 6-phosphate + Pi

In gluconeogenesis 3-PG is produced by enolase and phosphoglycerate mutase acting in series

PEP + H2O ⇌ 2-PG ⇌ 3-PG

In the Calvin cycle 3-PG is produced by RuBisCO

RuBP + CO2 + H2O → 2(3-PG)

G3P is produced by

glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in gluconeogenesis, and in series with glyceraldehyde-3-phosphate dehydrogenase (NADP+) (phosphorylating)
in the Calvin cycle

3-PG + ATP ⇌ 1,3-bisphosphoglycerate + ADP
1,3-bisphosphoglycerate + NAD(P)H + H+ ⇌ G3P + Pi + NAD(P)+

Triose-phosphate isomerase
maintains DHAP and G3P in near equilibrium, producing the mixture called triose phosphate (TP)

G3P ⇌ DHAP

Thus both DHAP and G3P are available to aldolase.

Moonlighting properties

Aldolase has also been implicated in many "moonlighting" or non-catalytic functions, based upon its binding affinity for many other proteins including

Band 3 anion exchanger, phospholipase D (PLD2), glucose transporter GLUT4, inositol trisphosphate, V-ATPase and ARNO (a guanine nucleotide exchange factor of ARF6). These associations are thought to be predominantly involved in cellular structure, however, involvement in endocytosis, parasite invasion, cytoskeleton rearrangement, cell motility, membrane protein trafficking and recycling, signal transduction and tissue compartmentalization have been explored.[8][9][10]

References

  1. .
  2. .
  3. ^ Trung Hieu Pham, Shreesha Rao, Ta-Chih Cheng, Pei-Chi Wang, Shih-Chu Chen, The moonlighting protein fructose 1,6-bisphosphate aldolase as a potential vaccine candidate against Photobacterium damselae subsp. piscicida in Asian sea bass (Lates calcarifer), Developmental & Comparative Immunology,Volume 124,2021,104187,ISSN 0145-305X,https://doi.org/10.1016/j.dci.2021.104187.
  4. PMID 11387336
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Further reading

External links