Cofactors

FMN; Heme b.

Reaction Mechanism

L-lactate dehydrogenase (cytochrome) By Reference

The flavo-cytochrome enzyme is a lactate dehydrogenase that catalyses the transfer of a hydride equivalent from its hydroxy acid substrate to the enzyme bound flavin, and thence to proteins of the mitochondrial electron transport chain via a bound cytochrome. The enzyme contains two domains, the flavin domain, capable of converting lactate to pyruvate by itself, and the heme domain which contains the prosthetic group involved in electron transfer from the reduced flavin to an acceptor cytochrome.




• Summary
• Step 1
• Step 2
• Step 3
• Step 4
• Step 5
• Step 6
• Products

The enzyme catalyses the oxidation of lactate to pyruvate. In the wild type enzyme the OH and CH bond cleavages in lactate are highly asynchronous. The lactate hydroxyl proton is abstracted by His 373 to form the alkoxide either early in the reaction or in a pre-equilibrium. The developing charge on the oxygen is stabilised by Tyr254. The hydride is then transferred to the flavin, forming pyruvate.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
Tyr	P00175	334	1fcb	254
Asp	P00175	362	1fcb	282
His	P00175	453	1fcb	373

Step Components

overall reactant used, overall product formed, radical formation, proton transfer, radical termination, native state of cofactor regenerated, intermediate formation, aromatic bimolecular nucleophilic addition, bimolecular elimination, native state of enzyme regenerated, inferred reaction step, cofactor used, electron transfer, hydride transfer



Step 1.

His373 deprotonates the alcohol of the lactate which eliminates a hydride ion that is added to FAD.



Step 2.

A single electron is transferred from the FAD to the haem cofactor.



Step 3.

The haem cofactor transfers the electron to ferricytochrome c.



Step 4.

Water deprotonates the FAD, initiating the second single electron transfer from FAD to the haem cofactor.



Step 5.

The haem cofactor transfers the electron to ferricytochrome c.



Step 6.

Water deprotonates His373 in an inferred return step.



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Citations

• (R/S)-lactate/2-hydroxybutyrate dehydrogenases in and biosynthesis of block copolyesters by Ralstonia eutropha.
• Lactate metabolism in neurodegenerative diseases.
• Electrochemical characterization of a dual cytochrome-containing lactate dehydrogenase.
• Regulation of Mitochondrial Respiration by Hydrogen Sulfide.
• Bioenergetic alteration in gastrointestinal cancers: The good, the bad and the ugly.
• The role of lactate in cardiovascular diseases.
• Acid tolerance of lactate-utilizing bacteria of the order Bacteroidales contributes to prevention of ruminal acidosis in goats adapted to a high-concentrate diet.
• Lactate oxidation is linked to energy conservation and to oxygen detoxification via a putative terminal cytochrome oxidase in Methanosarcina acetivorans.
• Moderate Effects of Hypoxic Training at Low and Supramaximal Intensities on Skeletal Muscle Metabolic Gene Expression in Mice.
• The Link between Trace Metal Elements and Glucose Metabolism: Evidence from Zinc, Copper, Iron, and Manganese-Mediated Metabolic Regulation.
• Anti-parasitic drug discovery against Babesia microti by natural compounds: an extensive computational drug design approach.