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Lactate dehydrogenase A

  (Redirected from LDHA)

Lactate dehydrogenase A (LDHA) is an enzyme which in humans is encoded by the LDHA gene.[5] It is a monomer of lactate dehydrogenase, which exists as a tetramer. The other main subunit is lactate dehydrogenase B (LDHB).

LDHA
Protein LDHA PDB 1i10.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesLDHA, GSD11, HEL-S-133P, LDH1, LDHM, PIG19, lactate dehydrogenase A
External IDsMGI: 96759 HomoloGene: 56495 GeneCards: LDHA
Gene location (Human)
Chromosome 11 (human)
Chr.Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for LDHA
Genomic location for LDHA
Band11p15.1Start18,394,560 bp[1]
End18,408,425 bp[1]
RNA expression pattern
PBB GE LDHA 200650 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001135239
NM_001165414
NM_001165415
NM_001165416
NM_005566

NM_001136069
NM_010699

RefSeq (protein)

NP_001128711
NP_001158886
NP_001158887
NP_001158888
NP_005557

NP_001129541
NP_034829

Location (UCSC)Chr 11: 18.39 – 18.41 MbChr 7: 46.84 – 46.86 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Contents

FunctionEdit

Lactate dehydrogenase A catalyzes the inter-conversion of pyruvate and L-lactate with concomitant inter-conversion of NADH and NAD+. LDHA is found in most somatic tissues, though predominantly in muscle tissue and tumours, and belongs to the lactate dehydrogenase family. It has long been known that many human cancers have higher LDHA levels compared to normal tissues. It has also been shown that LDHA plays an important role in the development, invasion and metastasis of malignancies. Mutations in LDHA have been linked to exertional myoglobinuria.[6]

Interactive pathway mapEdit

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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|{{{bSize}}}px|alt=Glycolysis and Gluconeogenesis edit]]
Glycolysis and Gluconeogenesis edit
  1. ^ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".

Model organismsEdit

Model organisms have been used in the study of LDHA function. A conditional knockout mouse line, called Ldhatm1a(EUCOMM)Wtsi[14][15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty seven tests were carried out on mutant mice and five significant abnormalities were observed.[12] Few homozygous mutant embryos were identified during gestation, and none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice. Animals of both sex had abnormal plasma chemistry, males also had improved glucose tolerance and increased red blood cell distribution width.[12]

LDHAEdit

The following compounds have been demonstrated to inhibit the LDHA enzyme:

ReferencesEdit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000134333 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000063229 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Chung FZ, Tsujibo H, Bhattacharyya U, Sharief FS, Li SS (November 1985). "Genomic organization of human lactate dehydrogenase-A gene". Biochemical Journal. 231 (3): 537–41. PMC 1152784. PMID 3000353.
  6. ^ "Entrez Gene: LDHA lactate dehydrogenase A".
  7. ^ "Glucose tolerance test data for Ldha". Wellcome Trust Sanger Institute.
  8. ^ "Clinical chemistry data for Ldha". Wellcome Trust Sanger Institute.
  9. ^ "Haematology data for Ldha". Wellcome Trust Sanger Institute.
  10. ^ "Salmonella infection data for Ldha". Wellcome Trust Sanger Institute.
  11. ^ "Citrobacter infection data for Ldha". Wellcome Trust Sanger Institute.
  12. ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  13. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  14. ^ "International Knockout Mouse Consortium".
  15. ^ "Mouse Genome Informatics".
  16. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  17. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  18. ^ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  19. ^ van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
  20. ^ Miskimins WK, Ahn HJ, Kim JY, Ryu S, Jung YS, Choi JY (2014). "Synergistic anti-cancer effect of phenformin and oxamate". PLoS One. 9 (1): e85576. Bibcode:2014PLoSO...985576M. doi:10.1371/journal.pone.0085576. PMC 3897486. PMID 24465604.
  21. ^ Lu QY, Zhang L, Yee JK, Go VW, Lee WN (February 2015). "Metabolic Consequences of LDHA inhibition by Epigallocatechin Gallate and Oxamate in MIA PaCa-2 Pancreatic Cancer Cells". Metabolomics. 11 (1): 71–80. doi:10.1007/s11306-014-0672-8. PMC 4523095. PMID 26246802.
  22. ^ Billiard J, Dennison JB, Briand J, Annan RS, Chai D, Colón M, Dodson CS, Gilbert SA, Greshock J, Jing J, Lu H, McSurdy-Freed JE, Orband-Miller LA, Mills GB, Quinn CJ, Schneck JL, Scott GF, Shaw AN, Waitt GM, Wooster RF, Duffy KJ (September 2013). "Quinoline 3-sulfonamides inhibit lactate dehydrogenase A and reverse aerobic glycolysis in cancer cells". Cancer & Metabolism. 1 (1): 19. doi:10.1186/2049-3002-1-19. PMC 4178217. PMID 24280423.

Further readingEdit