Aldolase A

Aldolase A, fructose-bisphosphate
File:Fructose-1,6-bisphosphate aldolase 4ALD wpmp.png PDB rendering based on 4ALD.
Available structures PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB List of PDB id codes 1ado​, 1ald​, 1ewd​, 1ewe​, 1ewg​, 1ex5​, 1j4e​, 1zah​, 1zai​, 1zaj​, 1zal​, 2ald​, 2ot0​, 2ot1​, 4ald​, 6ald​
Identifiers
Symbols	ALDOA ; ALDA; MGC10942; MGC17716; MGC17767
External IDs	Template:OMIM5 Template:MGI HomoloGene: 68996
Gene ontology Molecular function Template:GNF GO Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

Aldolase A is an enzyme which catalyses one of the aldol reactions: 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 which encode the same protein.

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 catylitic 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;

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.CS1 maint: Multiple names: authors list (link)
• 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. 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. PMID 1353685.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". J. Infect. 24 (3): 317–20. 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. PMID 1999195.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Gamblin SJ, Davies GJ, Grimes JM; et al. (1991). "Activity and specificity of human aldolases". J. Mol. Biol. 219 (4): 573–6. PMID 2056525.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Multiple names: authors list (link)
• 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. PMID 2335208.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. PMID 2825199.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. PMID 3030757.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Inagaki H, Haimoto H, Hosoda S, Kato K (1988). "Aldolase C is localized in neuroendocrine cells". Experientia. 44 (9): 749–51. PMID 3046960.CS1 maint: Multiple names: authors list (link)
• 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. PMID 3355497.CS1 maint: Multiple names: authors list (link)
• 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. PMID 3391172.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. PMID 3441006.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. PMID 3570299.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. PMID 3674018.CS1 maint: Multiple names: authors list (link)
• 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. PMID 3840020.CS1 maint: Multiple names: authors list (link)
• 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. PMID 6406231.CS1 maint: Multiple names: authors list (link)

External links

• http://pdbdev.sdsc.edu:48346/pdb/molecules/pdb50_5.html
• Fructose-Bisphosphate+Aldolase at the US National Library of Medicine Medical Subject Headings (MeSH)
• ALDOA
• EC 4.1.2.13