|Gene:||ALDOA||Accession Number: HS07647 (MetaCyc)|
Synonyms: ALDA, Lung cancer antigen NY-LU-1, Muscle-type aldolase
Species: Homo sapiens
The human fructose bisphosphate aldolase A, B and C genes encode enzymes that catalyze the cleavage of fructose-1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate in glycolysis, the condensation of dihydroxyacetone phosphate and glyceraldehyde-3-phosphate to fructose-1,6-bisphosphate in gluconeogenesis, and fructose-1-phosphate into dihydroxyacetone phosphate and glyceraldehyde in fructose metabolism [Sakakibara89].
The human enzymes, fructose-bisphosphate aldolase A, fructose-bisphosphate aldolase B and fructose-bisphosphate aldolase C are members of the type I aldolase family which utilize a reaction mechanism involving the formation of a covalent Shiff base intermediate between the sugar and enzyme [Choi99]. The type II aldolases are more prevalent in prokaryotes and required cationic metal cofactors to complex with substrate in the active site. These enzymes have been studied as targets for interfering with glycolysis in Trypanosomes, as this is the only source of energy for this parasite when present in human blood [Azema06, Caceres10].
All three isomers are functional in the cytosol as homotetramers, but exhibit distinct developmental and tissue specific expression patterns; aldolase A is expressed in muscle and red blood cells, aldolase B in liver, kidney and small intestine, and aldolase C in brain, smooth muscle and neuronal tissue. These enzymes arose from a common ancestral gene; the family expanded by gene duplications, aldolase B diverged first with aldolase A being the most distantly related [Izzo88]. There is some indication that these enzymes can translocate to the nucleus as a likely regulatory mechanism to rapidly control cytosolic levels of hexose sugars [Mamczur08].
Aldolase A (muscle aldolase) is expressed in muscle and erythrocytes and human mutations have been identified resulting in myopathy and hemolytic anemia [Kreuder96]. This deficiency is well characterized and recognized as glycogen storage disease type 12 (OMIM: 611881). Aldolase A is highly abundant in muscle (comprising up to 5% of muscle protein) and mutations can result in a rare rhabdomyolytis causing degradation of the muscle and kidney failure [Kishi87].
|Map Position: [30,386,996 -> 30,404,259] (33.31 centisomes)|
Unification Links: ArrayExpress:P04075 , Entrez-gene:226 , Entrez:AAA51690 , Entrez:AAA51697 , Entrez:AAH04333 , Entrez:AAH10660 , Entrez:AAH12880 , Entrez:AAH13614 , Entrez:AAH15888 , Entrez:AAH16800 , Entrez:CAA28861 , Entrez:CAA29654 , Entrez:CAA30979 , Mint:MINT-4998828 , PDB:1ALD , PDB:2ALD , PDB:4ALD , PhosphoSite:P04075 , Pride:P04075 , Protein Model Portal:P04075 , SMR:P04075 , String:9606.ENSP00000336927 , UniProt:P04075
|Biological Process:||GO:0006000 - fructose metabolic process
GO:0006096 - glycolytic process
GO:0006941 - striated muscle contraction
|Molecular Function:||GO:0004332 - fructose-bisphosphate aldolase activity
GO:0016829 - lyase activity
Created 15-Jun-2010 by SRI International
Enzymatic reaction of: fructose-bisphosphate aldolase
EC Number: 184.108.40.206
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.
This reaction is reversible.
Enzymatic reaction of: fructose bisphosphate aldolase (fructose-bisphosphate aldolase A)
EC Number: 220.127.116.11
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.
The reaction is favored in the direction shown.
In Pathways: sucrose degradation V (sucrose α-glucosidase)
Azema06: Azema L, Lherbet C, Baudoin C, Blonski C (2006). "Cell permeation of a Trypanosoma brucei aldolase inhibitor: evaluation of different enzyme-labile phosphate protecting groups." Bioorg Med Chem Lett 16(13);3440-3. PMID: 16632348
Caceres10: Caceres AJ, Michels PA, Hannaert V (2010). "Genetic validation of aldolase and glyceraldehyde-3-phosphate dehydrogenase as drug targets in Trypanosoma brucei." Mol Biochem Parasitol 169(1);50-4. PMID: 19748525
Choi99: Choi KH, Mazurkie AS, Morris AJ, Utheza D, Tolan DR, Allen KN (1999). "Structure of a fructose-1,6-bis(phosphate) aldolase liganded to its natural substrate in a cleavage-defective mutant at 2.3 A(,)." Biochemistry 38(39);12655-64. PMID: 10504235
Izzo88: Izzo P, Costanzo P, Lupo A, Rippa E, Paolella G, Salvatore F (1988). "Human aldolase A gene. Structural organization and tissue-specific expression by multiple promoters and alternate mRNA processing." Eur J Biochem 174(4);569-78. PMID: 3391172
Kishi87: Kishi H, Mukai T, Hirono A, Fujii H, Miwa S, Hori K (1987). "Human aldolase A deficiency associated with a hemolytic anemia: thermolabile aldolase due to a single base mutation." Proc Natl Acad Sci U S A 84(23);8623-7. PMID: 2825199
Kreuder96: Kreuder J, Borkhardt A, Repp R, Pekrun A, Gottsche B, Gottschalk U, Reichmann H, Schachenmayr W, Schlegel K, Lampert F (1996). "Brief report: inherited metabolic myopathy and hemolysis due to a mutation in aldolase A." N Engl J Med 334(17);1100-4. PMID: 8598869
Sakakibara89: Sakakibara M, Takahashi I, Takasaki Y, Mukai T, Hori K (1989). "Construction and expression of human aldolase A and B expression plasmids in Escherichia coli host." Biochim Biophys Acta 1007(3);334-42. PMID: 2649152
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