Fructose Bisphosphate Aldolase

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Human fructose 1,6-bisphosphate aldolase complex with fructose 1,6-bisphosphate , 4ald

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Isotopic labelling has revealed the rate-determining step for the reaction. Either the carbon-carbon bond cleavage or the release of glyceraldehyde-3-phosphate comprise the slow step of the catalysis reaction; however, studies do indicate that the GAP release is likely the slowest step.[3]

It has been shown that aldolase is inhibited allosterically by oxidized glutathione, which is an oxidizing species biologically present. The glutathione oxidizes a thiol 25 angstroms from the catalytic site, which subsequently causes a drop in catalytic activity. In addition, the enzyme shows no positive cooperativity, despite being an oligomer. In fact, kinetics data actually show that the enzyme exhibits negative cooperativity. Thus the catalysis is highly compartmentalized within each subunit and binding causes little distal change of the enzymes structure.[5]


The regulation of fructose 1,6-bisphosphate aldolase is not well understood, but the understanding is every-increasing. As it is currently observed, aldolase C appears to be regulated mainly by the gene expression--the concentration of mRNA in the cytoplasm.[6] It is also known that adenosine 3',5'-cyclicmonophosphate (cAMP) affects the expression of the gene. cAMP concentration has been positively correlated with aldolase C expression. It is believed that cAMP acts upon a section of the promotor region, distal element D, causing the transcriptional promoter, NGFI-B, to bind. Once bound, the promoter activates the transcription of the gene coding for fructose bisphosphate aldolase.[7] Given the inhibitory effects of an oxidant in the presence of aldolase, it is possible that this could be a mechanism of regulation of the enzyme. The deactivation that accompanies the oxidation of the surface thiol of Cys72 could be used intracellularly to slow the catalysis of the enzyme and regulate glycolysis.[5]

3D structures of fructose 1,6-bisphophate aldolase


Additional Resources

For additional information, see: Carbohydrate Metabolism


  1. 1.0 1.1 1.2 Voet, D, Voet, J, & Pratt, C. (2008). Fundamentals of biochemistry, third edition. Hoboken, NJ: Wiley & Sons, Inc.
  2. Protein: fructose-1,6-bisphosphate aldolase from human (homo sapiens), muscle isozyme. (2009). Retrieved from
  3. 3.0 3.1 3.2 Gefflaut, T., B. Casimir, J. Perie, and M. Willson. "Class I Aldolases: Substrate Specificity, Mechanism, Inhibitors and Structural Aspects." Prog. Biophys. molec. Biol.. 63. (1995): 301-340.
  4. Dalby A, Dauter Z, Littlechild JA. Crystal structure of human muscle aldolase complexed with fructose 1,6-bisphosphate: mechanistic implications. Protein Sci. 1999 Feb;8(2):291-7. PMID:10048322
  5. 5.0 5.1 Sygusch, J., and Beaudry, D. "Allosteric communication in mammalian muscle aldolase." Biochem. J.. 327. (1997): 717-720.
  6. Paolella, G, Buono, P, Mancini, F P, Izzo, P, and Salvatore, F. "Structure and expression of mouse aldolase genes." Eur. J. Biochem.. 156. (1986): 229-235.
  7. Buono, P, Cassano, S, Alfieri, A, Mancini, A, and Salvatore, F. "Human aldolase C gene expression is regulated by adenosine 30,50-cyclic monophosphate (cAMP) in PC12 cells." Gene. 291. (2002): 115-121.

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