Enzyme

1.1.1.27 - L-lactate dehydrogenase

Alternative Name(s)
  • L-lactic acid dehydrogenase.
  • L-lactic dehydrogenase.

Catalytic Activity

(S)-lactate + NAD(+) = H(+) + NADH + pyruvate

Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

    Lactate dehydrogenase catalyses the interconversion of L-lactate and pyruvate in the glycolytic pathway, coupled with the reduction/oxidation of NAD+ and NADH. The enzyme crystallised from dogfish is a homotetramer. There has been some debate about whether the enzyme mechanism is concerted or stepwise.

    In the forward direction a proton is abstracted from lactate and a hydride donated to NAD+. In the reverse direction a proton is donated to pyruvate and a hydride ion donated from NADH. The proton donor/abstractor depending on direction is His193, which is regulated via hydrogen-bond to Asp166. The hydride is donated/abstracted by NADH/NAD+. It is likely that the reaction proceeds in a stepwise manner with Arg169 stabilising the charge via a strong salt bridge to the substrate, and possibly via electrostatic interactions from Arg106.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    His P00341 194 1ldm 193
    Arg P00341 107 1ldm 106
    Arg P00341 170 1ldm 169
    Asp P00341 167 1ldm 166
    Step Components

    overall reactant used, proton transfer, overall product formed, native state of enzyme regenerated, inferred reaction step, cofactor used, hydride transfer

    Step 1.

    His193 abstracts a proton from the hydroxyl group of the substrate. NAD accepts a hydride in a nucleophilic addition reaction.

    Step 2.

    In an inferred step his193 is deprotonated to regenerate the native state of the enzyme.

    Products.

    The products of the reaction.

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Protein name Organism
Probable L-lactate dehydrogenase Fission yeast
L-lactate dehydrogenase B-A chain Zebrafish
L-lactate dehydrogenase 1 Staphylococcus aureus (strain Newman)
L-lactate dehydrogenase B-B chain Zebrafish
L-lactate dehydrogenase A-like 6B Human

Citations