Aldolase A

Aldolase A, fructose-bisphosphate
PDB rendering based on 4ALD.
Available structures PDB 1ALD, 2ALD, 4ALD
Identifiers
Symbols	ALDOA; ALDA; GSD12
External IDs	OMIM: 103850 MGI: 87994 HomoloGene: 123896 GeneCards: ALDOA Gene
EC number	4.1.2.13
Gene Ontology Molecular function • actin binding • fructose-bisphosphate aldolase activity • cytoskeletal protein binding • tubulin binding • lyase activity • identical protein binding • fructose binding Cellular component • extracellular region • cytosol • actin cytoskeleton • platelet alpha granule lumen • I band • extracellular vesicular exosome Biological process • platelet degranulation • carbohydrate metabolic process • fructose metabolic process • glucose metabolic process • gluconeogenesis • glycolysis • glycolysis • ATP biosynthetic process • striated muscle contraction • actin filament organization • blood coagulation • regulation of cell shape • platelet activation • fructose 1,6-bisphosphate metabolic process • small molecule metabolic process • muscle cell homeostasis • protein homotetramerization Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	226	11674
Ensembl	ENSG00000149925	ENSMUSG00000030695
UniProt	P04075	P05064
RefSeq (mRNA)	NM_000034.3	NM_001177307.1
RefSeq (protein)	NP_000025.1	NP_001170778.1
Location (UCSC)	Chr 16: 30.06 – 30.08 Mb	Chr 7: 133.94 – 133.94 Mb
PubMed search	[1]	[2]

fructose-bisphosphate aldolase
Identifiers
EC number	4.1.2.13
CAS number	9024-52-6
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles

Aldolase A is an enzyme that catalyses a reverse aldol reaction: The substrate, fructose 1,6-bisphosphate (F-1,6-BP) is broken down into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP). This reaction is a part of glycolysis. Three aldolase isozymes (A, B, and C), encoded by three different genes, are differentially expressed during development. Aldolase A is found in the developing embryo and is produced in even greater amounts in adult muscle. Aldolase A expression is repressed in adult liver, kidney, and intestine and similar to aldolase C levels in brain and other nervous tissue. Aldolase A deficiency has been associated with myopathy and hemolytic anemia. Alternative splicing of this gene results in multiple transcript variants that encode the same protein.

β-D-fructose 1,6-phosphate	fructose bisphosphate aldolase		D-glyceraldehyde 3-phosphate		dihydroxyacetone phosphate
				+
	fructose bisphosphate aldolase

Compound C05378 at KEGG Pathway Database. Enzyme 4.1.2.13 at KEGG Pathway Database. Compound C00111 at KEGG Pathway Database. Compound C00118 at KEGG Pathway Database.

The numbering of the carbon atoms indicates the fate of the carbons according to their position in fructose 6-phosphate.

Mechanism

In mammalian aldolase, the key catalytic amino acid residues involved in the reaction are lysine and tyrosine. The tyrosine acts as an efficient hydrogen acceptor while the lysine covalently binds and stabilizes the intermediates. Many bacteria use two magnesium ions in place of the lysine.

The reaction mechanism of aldolase. The enzyme's reactive site amino acid's side-chains are shown in blue. Abbreviations: DHAP - dihydroxyacetone phosphate; Fru1,6bP - Fructose-1,6-bisphosphate; GAD - glyceraldehyde 3-phosphate;

Interactions

Aldolase A has been shown to interact with PLD2.

Further reading

• Pfleiderer G, Thöner M, Wachsmuth ED (1976). "Histological examination of the aldolase monomer composition of cells from human kidney and hypernephroid carcinoma". Beiträge zur Pathologie 156 (3): 266–79. PMID 766744. 
• Rehbein-Thöner M, Pfleiderer G (1977). "The changes in aldolase isoenzyme pattern during development of the human kidney and small intestine--demonstrated in organ extracts and tissue sections". Hoppe-Seyler's Z. Physiol. Chem. 358 (2): 169–80. PMID 844801. 
• Wachsmuth ED (1976). "Differentiation of epithelial cells in human jejunum: localization and quantification of aminopeptidase, alkaline phosphatase and aldolase isozymes in tissue sections". Histochemistry 48 (2): 101–9. doi:10.1007/BF00494548. PMID 955981. 
• Lee KN, Maxwell MD, Patterson MK, et al. (1992). "Identification of transglutaminase substrates in HT29 colon cancer cells: use of 5-(biotinamido)pentylamine as a transglutaminase-specific probe". Biochim. Biophys. Acta 1136 (1): 12–6. doi:10.1016/0167-4889(92)90078-P. PMID 1353685. 
• Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". J. Infect. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151. 
• Mukai T, Arai Y, Yatsuki H, et al. (1991). "An additional promoter functions in the human aldolase A gene, but not in rat". Eur. J. Biochem. 195 (3): 781–7. doi:10.1111/j.1432-1033.1991.tb15766.x. PMID 1999195. 
• Gamblin SJ, Davies GJ, Grimes JM, et al. (1991). "Activity and specificity of human aldolases". J. Mol. Biol. 219 (4): 573–6. doi:10.1016/0022-2836(91)90650-U. PMID 2056525. 
• Vértessy BG, Orosz F, Ovádi J (1991). "Modulation of the interaction between aldolase and glycerol-phosphate dehydrogenase by fructose phosphates". Biochim. Biophys. Acta 1078 (2): 236–42. PMID 2065091. 
• Takasaki Y, Takahashi I, Mukai T, Hori K (1990). "Human aldolase A of a hemolytic anemia patient with Asp-128----Gly substitution: characteristics of an enzyme generated in E. coli transfected with the expression plasmid pHAAD128G". J. Biochem. 108 (2): 153–7. PMID 2229018. 
• Gamblin SJ, Cooper B, Millar JR, et al. (1990). "The crystal structure of human muscle aldolase at 3.0 A resolution". FEBS Lett. 262 (2): 282–6. doi:10.1016/0014-5793(90)80211-Z. PMID 2335208. 
• Kishi H, Mukai T, Hirono A, et al. (1988). "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. doi:10.1073/pnas.84.23.8623. PMC 299598. PMID 2825199. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=299598. 
• Izzo P, Costanzo P, Lupo A, et al. (1987). "A new human species of aldolase A mRNA from fibroblasts". Eur. J. Biochem. 164 (1): 9–13. doi:10.1111/j.1432-1033.1987.tb10984.x. PMID 3030757. 
• Inagaki H, Haimoto H, Hosoda S, Kato K (1988). "Aldolase C is localized in neuroendocrine cells". Experientia 44 (9): 749–51. doi:10.1007/BF01959149. PMID 3046960. 
• Freemont PS, Dunbar B, Fothergill-Gilmore LA (1988). "The complete amino acid sequence of human skeletal-muscle fructose-bisphosphate aldolase". Biochem. J. 249 (3): 779–88. PMC 1148774. PMID 3355497. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1148774. 
• Izzo P, Costanzo P, Lupo A, et al. (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. doi:10.1111/j.1432-1033.1988.tb14136.x. PMID 3391172. 
• Maire P, Gautron S, Hakim V, et al. (1988). "Characterization of three optional promoters in the 5' region of the human aldolase A gene". J. Mol. Biol. 197 (3): 425–38. doi:10.1016/0022-2836(87)90556-0. PMID 3441006. 
• Kukita A, Yoshida MC, Fukushige S, et al. (1987). "Molecular gene mapping of human aldolase A (ALDOA) gene to chromosome 16". Hum. Genet. 76 (1): 20–6. doi:10.1007/BF00283044. PMID 3570299. 
• Tolan DR, Niclas J, Bruce BD, Lebo RV (1987). "Evolutionary implications of the human aldolase-A, -B, -C, and -pseudogene chromosome locations". Am. J. Hum. Genet. 41 (5): 907–24. PMC 1684339. PMID 3674018. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1684339. 
• Sakakibara M, Mukai T, Hori K (1985). "Nucleotide sequence of a cDNA clone for human aldolase: a messenger RNA in the liver". Biochem. Biophys. Res. Commun. 131 (1): 413–20. doi:10.1016/0006-291X(85)91818-2. PMID 3840020. 
• Ovádi J, Mohamed Osman IR, Batke J (1983). "Interaction of the dissociable glycerol-3-phosphate dehydrogenase and fructose-1,6-bisphosphate aldolase. Quantitative analysis by an extrinsic fluorescence probe". Eur. J. Biochem. 133 (2): 433–7. doi:10.1111/j.1432-1033.1983.tb07482.x. PMID 6406231. 

External links

• http://pdbdev.sdsc.edu:48346/pdb/molecules/pdb50_5.html
• MeSH Fructose-Bisphosphate+Aldolase
• ALDOA
• EC 4.1.2.13