Lactate Dehydrogenase

Function L-lactate dehydrogenase (L-LDH) catalyzes the interconversion of pyruvate and NADH+ to L-lactate and NAD+. H-lactate dehydrogenase (H-LDH) catalyzes the interconversion of D-lactate and ferricytochrome c to pyruvate and ferrocytochrome c. Lactate Dehydrogenase (LDH) is an important enzyme in humans. It occurs in different regions of the body, each region having a unique conformation of different subunits. LDH is a key enzyme in anaerobic respiration. Anaerobic Respiration is the in the absence oxygen. This pathway is important to glycolysis in two main ways. The first is that if pyruvate were to build up glycoysis and thus the generation of ATP would slow. The second is anaerobic respiration allows for the regeneration of NAD+ from NADH. NAD+ is required when glyceraldehyde-3-phosphate dehydrogenase oxidizes glyceraldehyde-3-phosphate in glycolysis, which generates NADH. Lactate dehydrogenase is responsible for the anaerobic conversion of NADH to NAD+. in the Lactate Dehydrogenase from Cryptosporidium parvum (4nd4). Human Lactate Dehydrogenase Structure is a quaternary protein formed of the combination of two subunits, M and H (Muscle and Heart) into a structure of four of the subunits. The various combinations found in the human body are: (4H) Heart (3H1M) Reticuloendothelial (2H2M) Lungs (1H3M) Kidneys (4M) Muscle and Liver The of LDH as shown here is comprised of 40% alpha helices and 23% beta sheets. The SCOP data classifies this form of lactate dehydrogenase as mixed beta-alpha-beta, with mainly parallel beta sheets. See Human Lactate Dehydrogenase. See Rossmann fold. Catalysis Studies have shown that the reaction mechanism of LDH follows an ordered sequence. In order for lactate to be oxidized NADH must bind to the enzyme first followed by lactate. . Once the NADH is bound to the enzyme, it is then possible for lactate to bind (substrate oxamate is shown; the ‑CH3 group is replaced by ‑NH2 to form oxamate). Lactate binds to the enzyme between the nicotinamide ring and several LDH residues. Transfer of a hydride ion then happens quickly in either direction giving a mixture of the two tertiary complexes, enzyme-NAD+-lactate and enzyme-NADH-pyruvate .Finally pyruvate dissociates from the enzyme followed by NAD+. Kinetics Kinetic studies of lactate dehydrogenase with oxalate and oxamate (structural analogues of lactate and pyruvate)have proven the mechanism stated above. The rate limiting step in this reaction is the rate of dissociation of NAD+ and NADH. The conversion of pyruvate to lactate with the subsequent regeneration of NAD+ is very favorable. Regulation As the mechanism is one of equilibrium, There appears to be no regulation specifically designed for lactate dehydrogenase, instead it is dependent on the activation of anaerobic reparation and the presence of pyruvate and NADH, or lactate and NAD+.

spinqualitylabelsall models Lactate dehydrogenase dimer complex with cofactor NAD and pyruvate (PDB code 4nd4) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D structures of lactate dehydrogenase3D structures of lactate dehydrogenase

Updated on 20-January-2019

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• L-LDH
  • 2e37, 2v6m – TtL-LDH – Thermus thermophilus
    
  • 3zzn, 4a73– TtL-LDH (mutant)
    
  • 2x8l, 1ceq – PfL-LDH – Plasmodium falciparum
    
  • 2zqy, 2zqz, 1llc – LcL-LDH – Lactobacillus casei
    
  • 3vku - LcL-LDH (mutant)
    
  • 3d0o - SaL-LDH – Staphylococcus aureus
    
  • 2v65 - L-LDH A chain – Champsocephalus gunnari
    
  • 2v6b – L-LDH – Deinococcus radiodurans
    
  • 4nd5 – CpLDH – Cryptosporidium parvum
    
  • 1sov, 1pze - TgL-LDH – Toxoplasma gondii
    
  • 1v6a – L-LDH A chain – Cyprinus carpio
    
  • 1y6j – L-LDH – Clostridium thermocellum
    
  • 1ldb - GsL-LDH – Geobacillus stearothermophilus
    
  • 1ldm, 6ldh, 8ldh – sdM4-LDH – spiny dogfish
    
  • 2ldx – C4-LDH - mouse
    
  • 4m1q - BseL-LDH – Bacillus selenitireducens
    
  • 3pqe – BsL-LDH (mutant) – Bacillus subtilis
    
  • 4lmr, 4ln1 - LDH – Bacillus cereus
    
  • 3vpg – TcLDH – Thermus caldophilus
    
  • 3wsv – EmLDH – Enteroccocus mundtii
    
  • 4l4r, 4ojn – hLDH A chain – human
    
  • 4uum – TvL-LDH – Trichomonas vaginalis
    
  • 4uul – TvL-LDH (mutant)
    
  • 5hs4 - PvL-LDH – Plasmodium vivax
    
  • 5k0z – LDH B chain – chicken
    
• L-LDH from yeast (cytochrome b2)
  • 1kbj - LDH FMN-binding domain
    
  • 1sze, 1lco, 2oz0 - LDH FMN-binding domain (mutant)
    
  • 1kbi - LDH FMN-binding domain + pyruvate
    
  • 1szf, 1ldc - LDH FMN-binding domain (mutant) + pyruvate
    
  • 1szg - LDH FMN-binding domain + sulfo-FMN
    
  • 3ks0 - LDH residues 86-180 + flavocytochrome b2 heme domain + FAB B2B4
• L-LDH binary complex
  • 4b7u – PfL-LDH + bicine
    
  • 1cet - PfL-LDH + chloroquine
    
  • 1t2c - PfL-LDH + NAD
    
  • 3zh2 - PfL-LDH + DNA aptamer
    
  • 1ez4 - L-LDH + NAD – Lactobacillus pentosus
    
  • 1lld, 2ldb - GsL-LDH + NAD
    
  • 2a92 – PvL-LDH + NAD
    
  • 2a94, 2aa3 - PvL-LDH + NAD-analog
    
  • 5hru, 5hto - PvL-LDH + DNA
    
  • 1u4o, 1u4s, 1u5a, 1xiv – PfL-LDH + inhibitor
    
  • 2xxb – TtL-LDH (mutant) + AMP
    
  • 3pqf – BsL-LDH (mutant) + NAD
    
  • 3vkv - LcLDH + fructose-bisphosphate
    
  • 3vpf – LcLDH (mutant) + pyruvate
    
  • 4aj1, 4aj2, 4aj4, 4aje, 4ajh, 4aji, 4ajj, 4ajk, 4ajl, 4ajn, 4ajo, 4al4, 5kkc – raL-LDH A chain + inhibitor – rat
    
  • 5es3 – raL-LDH + oxamate
    
  • 5nqb – raL-LDH A chain (mutant) + malonate
    
  • 4ajp, 4m49, 4qsm, 4qt0, 5w8h, 5w8i, 5w8j – hLDH A chain + inhibitor
    
  • 4l4s – hLDH α chain + NAD
    
  • 4i8x, 4i9h, 4i9n, 4i9u – rLDH A chain + pyridine derivative - rabbit
    
  • 4uun – TvL-LDH + NAD
    
• L-LDH ternary complex with inhibitor
  • 1u5c - PfL-LDH + inhibitor + NAD
    
  • 1t24, 1t25, 1t26 - PfL-LDH + azole derivative + NAD
    
  • 1t2e - PfL-LDH (mutant) + oxamate + NAD
    
  • 1ldg, 4plz - PfL-LDH + oxamate + NAD
    
  • 1t2d - PfL-LDH + oxalate + NAD
    
  • 2xxj – TtL-LDH (mutant) + oxamate + NAD
    
  • 2v7p - TtL-LDH + oxamate + NAD
    
  • 3om9, 3czm – TgL-LDH + OXQ + NAD
    
  • 1sow, 1pzh - TgL-LDH + oxalate + NAD
    
  • 1pzf - TgL-LDH + oxalate + NAD-analog
    
  • 1pzg - TgL-LDH + sulfate + NAD-analog
    
  • 3h3f – rL-LDH A chain + oxamate + NAD
    
  • 5nqq - rL-LDH A chain + oxalacetate + NAD
    
  • 4nd1 - CpLDH + oxamate + NAD
    
  • 1t2f - hL-LDH B chain + azole derivative + NAD
    
  • 1i0z - hL-LDH H chain + oxamate + NAD
    
  • 1i10 - hL-LDH M chain + oxamate + NAD
    
  • 4qo7, 4qo8, 4r68, 4r69, 4rls, 4zvv, 5ixs, 5ixy, 5w8k, 5w8l - hL-LDH A chain + inhibitor + NAD
    
  • 3wsw – EmL-LDH + NAD + fructose diphosphate
    
  • 1oc4 – L-LDH + oxamate + NAD – Plasmodium berghei
    
  • 1a5z - L-LDH + oxamate + NAD – Thermotoga maritima
    
  • 1lth - L-LDH + oxamate + NAD – Bifidobacterium longum
    
  • 1ldn - GsL-LDH + oxamate + NAD
    
  • 9ldb, 9ldt, 6cep - pL-LDH + oxamate + NAD – pig
    
  • 4plc, 4plf – ApLDH + NAD + pyruvate - Apicomplexa
    
  • 4plg – ApLDH + NAD + oxamate
    
  • 5a1t – TvL-LDH + NAD + oxamate
    
• L-LDH ternary complex with reactants
  • 3h3j – SaL-LDH (mutant) + pyruvate + NAD
    
  • 3d4p - SaL-LDH + pyruvate + NAD
    
  • 2fn7 - CpLDH + lactate + NAD
    
  • 4nd2 - CpLDH + pyruvate + NAD-analog
    
  • 4nd4 - CpLDH + pyruvate + NAD
    
  • 5ldh - pLDH + citrate + NAD-analog
    
  • 3ldh - sdLDH + pyruvate + NAD
    
  • 3pqd - BsLDH + fructose-bisphosphate + NAD
• L-LDH quaternary complex
  • 4jnk - hL-LDH A chain + inhibitor + lactate + NAD
    
  • 4okn - hL-LDH A chain + katamycin+ oxalate + NAD
    
  • 3vph - TcL-LDH + oxamate + NAD + fructose diphosphate
    
• D-LDH
  • 3kb6 – D-LDH + lactate + NAD – Aquifex aeolicus
    
  • 1j49 – LdD-LDH + sulfate + NAD – Lactobacillus delbrueckii
    
  • 1j4a - LdD-LDH + sulfate
    
  • 1f0x – EcD-LDH + FAD – Escherichia coli
    
  • 2dld - D-LDH + oxamate + NAD – Lactobacillus helveticus
    
  • 3wwy – D-LDH – Fusobacterium nucleatum
    
  • 3wwz – D-LDH – Peudomonas aeruginosa
    
  • 4xkj – D-LDH + NAD – Sporolactobacillus inulinus
    
  • 4cuj – SeD-LDH – Salmonella enterica
    
  • 4cuk – SeD-LDH + NAD
    
• L-LDH II
  • 1x0a, 1vbi – TtL-LDH II
• L-Lactate/malate dehydrogenase
  • 1hye, 1hyg – L-LDH/MDH – Methanocaldococcus jannaschi
    
  • 2g8y - EcL-LDH/MDH

Additional InformationAdditional Information

For additional information, see Carbohydrate Metabolism

ReferenceReference

• 1- http://www.bioc.aecom.yu.edu/labs/calllab/highlights/LDH.htm
• 2- http://www.cheric.org/ippage/e/ipdata/2004/05/file/e200405-701.pdf
• 3- http://resources.metapress.com/pdf-preview.axd?code=ulnhp23038060m21&size=largest
• 4- http://www.u676.org/Documents/Chretien-ClinChimActa-95.pdf
• 5- http://www.jbc.org/content/243/17/4526.full.pdf+html