Enzyme - Tartronate-semialdehyde synthase

Alternative Name(s)
  • Tartronate semialdehyde carboxylase.
  • Glyoxylate carboligase.

Catalytic Activity

2 glyoxylate + H(+) = 2-hydroxy-3-oxopropanoate + CO2


Thiamine diphosphate.

Reaction Mechanism

    Glyoxylate carboligase, also called tartronate-semialdehyde synthase, releases carbon dioxide while synthesising a single molecule of tartronate semialdehyde from two molecules of glyoxylate. It is a thiamine pyrophosphate-dependent enzyme, closely related in sequence to the large subunit of acetolactate synthase. In the D-glycerate pathway, part of allantoin degradation in the Enterobacteriaceae, tartronate semialdehyde is converted to D-glycerate and then 3-phosphoglycerate, a product of glycolysis and entry point in the general metabolism.

    This enzyme utilises a thiamine diphosphate cofactor to catalyse the condensation reaction between two molecules of glyoxylate. The mechanism, however, does not begin with a proton transfer to a conserved gluatmate, as is the case for every other enzyme that uses this cofactor. Instead, the aliphatic residues surrounding the cofactor act to lower the dielectric constant of the active site, leading to activation of the cofactor by intramolecular proton rearrangement.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Leu P0AEP7 421 2pan 444
    Ile P0AEP7 479 2pan 502
    Leu P0AEP7 476 2pan 499
    Val P0AEP7 25 2pan 48
    Val P0AEP7 51 2pan 74
    Step Components

    overall reactant used, proton transfer, overall product formed, intramolecular elimination, bimolecular nucleophilic addition, native state of cofactor regenerated, intermediate formation, native state of enzyme regenerated, inferred reaction step, cofactor used

    Step 1.

    The cofactor undergoes an intramolecular proton transfer between the pyrimidine and thiazole ring, forming a carbon-nitrogen ylid.

    Step 2.

    The carbanion of thiamine diphosphate initiates a nucleophilic attack on the carbonyl carbon of glyoxylate in an addition reaction. The conjugated double bond system of the cofactor undergoes rearrangement.

    Step 3.

    The glyoxylate-TDP adduct undergoes decarboxylation with concomitant bond rearrangement on the thiazole ring. The aliphatic region around the cofactor encourages decarboxylation through polar, non-polar interactions, which act to increase the ground state energy of the intermediate towards that of the transition state [PMID:18176558, PMID:15501823, PMID:15709735]

    Step 4.

    The nitrogen of the thiazole ring initiates conjugate nucleophilic attack at the carbonyl of the second glyoxylate molecule, with inferred, concomitant, intramolecular proton rearrangement.

    Step 5.

    The oxyanion initiates elimination, forming the single S enantiomer of 2-Hydroxy-3-oxopropanoate and regenerating the activated form of the thiamine diphosphate cofactor.

    Step 6.

    Protonation at the C2 position regenerates the thiamine diphosphate cofactor, and the enzyme active site.


    The products of the reaction.

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Protein name Organism
Glyoxylate carboligase Escherichia coli (strain K12)
Carboxylase/decarboxylase/carboligase Streptomyces noursei ATCC 11455
Glyoxylate carboligase (Partial) Ralstonia solanacearum
Putative glyoxylate carboligase protein Ensifer meliloti
Uncharacterized protein - A0A0C5DTV9 Pseudomonas sp. MRSN12121