Lactate dehydrogenase A

LDHA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1I10, 4AJP, 4JNK, 4L4R, 4L4S, 4M49, 4OJN, 4OKN, 4QO7, 4QO8, 4QSM, 4QT0, 4R68, 4R69, 4RLS, 4ZVV
Identifiers
Aliases	LDHA , GSD11, HEL-S-133P, LDH1, LDHM, PIG19, lactate dehydrogenase A
External IDs	OMIM: 150000; MGI: 96759; HomoloGene: 56495; GeneCards: LDHA; OMA:LDHA - orthologs
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11p15.1 Start 18,394,560 bp [1] End 18,408,425 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7 B3|7 30.6 cM Start 46,490,899 bp [2] End 46,505,051 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone skin of leg tibial arteries skin of abdomen muscle of leg Achilles tendon epithelium of colon ascending aorta right adrenal gland gastrocnemius muscle Top expressed in otic placode somite primitive streak otic vesicle epiblast triceps brachii muscle vastus lateralis muscle sternocleidomastoid muscle medial head of gastrocnemius muscle saccule More reference expression data BioGPS More reference expression data
Gene ontology Molecular function oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor NAD binding lactate dehydrogenase activity kinase binding protein binding catalytic activity identical protein binding oxidoreductase activity L-lactate dehydrogenase activity cadherin binding Cellular component cytoplasm membrane extracellular exosome nucleus cytosol Biological process post-embryonic animal organ development lactate metabolic process response to hypoxia glycolytic process response to organic cyclic compound substantia nigra development response to nutrient carboxylic acid metabolic process response to glucose NAD metabolic process response to estrogen pyruvate metabolic process positive regulation of apoptotic process response to cAMP response to hydrogen peroxide carbohydrate metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3939 16828 Ensembl ENSG00000134333 ENSG00000288299 ENSMUSG00000063229 UniProt P00338 P06151 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 Mb Chr 7: 46.49 – 46.51 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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).

Function

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 tumors, 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 map

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

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|alt=Glycolysis and Gluconeogenesis edit]]

Glycolysis and Gluconeogenesis edit

1. The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".

LDHA Inhibitors

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

• Oxamate ^[7]
• Epigallocatechin gallate ^[8]
• Quinoline 3-sulfonamide ^[9]
• CHK-336 ^[10]

References

1. ENSG00000288299 GRCh38: Ensembl release 89: ENSG00000134333, ENSG00000288299 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000063229 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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. doi:10.1042/bj2310537. PMC   1152784 . PMID   3000353.
6. "Entrez Gene: LDHA lactate dehydrogenase A".
7. 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.
8. 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.
9. 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.
10. Cox, Jennifer H.; Boily, Marc-Olivier; Caron, Alex; Chefson, Amandine; Chong, Oliver; Ding, Jim; Dumais, Valerie; Gaudreault, Samuel; Gomez, Robert; Guthrie, James; Holmes, Ross P.; King, Andrew J.; Knight, John; Lester, Jeff; Lowther, W. T. (October 2020). "Discovery of CHK-336: A First-in-Class, Liver-Targeted, Small Molecule Inhibitor of Lactate Dehydrogenase for the Treatment of Primary Hyperoxaluria: PO1620" . Journal of the American Society of Nephrology. 31 (10S): 514. doi:10.1681/ASN.20203110S1514a. ISSN   1046-6673.

Further reading

• Miyajima H, Shimizu T, Kaneko E (October 1992). "[Gene expression in lactate dehydrogenase-A subunit deficiency]". Rinsho Shinkeigaku. 32 (10): 1087–92. PMID   1297552.
• Sudo K, Maekawa M, Shioya M, Ikeda K, Takahashi N, Isogai Y, Li SS, Kanno T, Machida K, Toriumi J (September 1992). "Molecular analysis of genetic mutation in electrophoretic variant of human lactate dehydrogenase-A(M) subunit". Biochemistry International. 27 (6): 1051–7. PMID   1445373.
• Maekawa M, Sudo K, Li SS, Kanno T (October 1991). "Analysis of genetic mutations in human lactate dehydrogenase-A(M) deficiency using DNA conformation polymorphism in combination with polyacrylamide gradient gel and silver staining". Biochemical and Biophysical Research Communications. 180 (2): 1083–90. Bibcode:1991BBRC..180.1083M. doi:10.1016/S0006-291X(05)81177-5. PMID   1953713.
• Maekawa M, Sudo K, Li SS, Kanno T (November 1991). "Genotypic analysis of families with lactate dehydrogenase A (M) deficiency by selective DNA amplification". Human Genetics. 88 (1): 34–8. doi:10.1007/BF00204925. PMID   1959923. S2CID   19321774.
• Scrable HJ, Johnson DK, Rinchik EM, Cavenee WK (March 1990). "Rhabdomyosarcoma-associated locus and MYOD1 are syntenic but separate loci on the short arm of human chromosome 11". Proceedings of the National Academy of Sciences of the United States of America. 87 (6): 2182–6. Bibcode:1990PNAS...87.2182S. doi: 10.1073/pnas.87.6.2182 . PMC   53650 . PMID   2315312.
• Maekawa M, Sudo K, Kanno T, Li SS (April 1990). "Molecular characterization of genetic mutation in human lactate dehydrogenase-A (M) deficiency". Biochemical and Biophysical Research Communications (Submitted manuscript). 168 (2): 677–82. Bibcode:1990BBRC..168..677M. doi:10.1016/0006-291X(90)92374-9. PMID   2334430.
• Gosti F, Marty MC, Courvalin JC, Maunoury R, Bornens M (February 1987). "Centrosomal proteins and lactate dehydrogenase possess a common epitope in human cell lines". Proceedings of the National Academy of Sciences of the United States of America. 84 (4): 1000–4. Bibcode:1987PNAS...84.1000G. doi: 10.1073/pnas.84.4.1000 . PMC   304349 . PMID   2434947.
• 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. doi:10.1042/bj2310537. PMC   1152784 . PMID   3000353.
• Tsujibo H, Tiano HF, Li SS (February 1985). "Nucleotide sequences of the cDNA and an intronless pseudogene for human lactate dehydrogenase-A isozyme". European Journal of Biochemistry. 147 (1): 9–15. doi: 10.1111/j.1432-1033.1985.tb08711.x . PMID   3838278.
• Glass RD, Doyle D (April 1972). "Genetic control of lactate dehydrogenase expression in mammalian tissues". Science. 176 (4031): 180–1. Bibcode:1972Sci...176..180G. doi:10.1126/science.176.4031.180. PMID   5014440. S2CID   20224553.
• Maekawa M, Sudo K, Kobayashi A, Sugiyama E, Li SS, Kanno T (April 1994). "Fast-type electrophoretic variant of lactate dehydrogenase M(A) and comparison with other missense mutations in lactate dehydrogenase M(A) and H(B) genes". Clinical Chemistry. 40 (4): 665–8. doi: 10.1093/clinchem/40.4.665 . PMID   7908613.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.
• Miyajima H, Takahashi Y, Suzuki M, Shimizu T, Kaneko E (July 1993). "Molecular characterization of gene expression in human lactate dehydrogenase-A deficiency". Neurology. 43 (7): 1414–9. doi:10.1212/wnl.43.7.1414. PMID   8327147. S2CID   41011165.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID   9373149.
• Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, Gure AO, Jäger D, Jäger E, Knuth A, Chen YT, Old LJ (November 1999). "Antigens recognized by autologous antibody in patients with renal-cell carcinoma". International Journal of Cancer. 83 (4): 456–64. doi: 10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5 . PMID   10508479.
• Vilà MR, Nicolás A, Morote J, de I, Meseguer A (July 2000). "Increased glyceraldehyde-3-phosphate dehydrogenase expression in renal cell carcinoma identified by RNA-based, arbitrarily primed polymerase chain reaction". Cancer. 89 (1): 152–64. doi:10.1002/1097-0142(20000701)89:1<152::AID-CNCR20>3.0.CO;2-T. PMID   10897012. S2CID   44477008.
• Boutet A, Altmeyer R, Héry C, Tardieu M (December 2000). "Direct role of plasma membrane-expressed gp120/41 in toxicity to human astrocytes induced by HIV-1-infected macrophages". AIDS. 14 (17): 2687–97. doi: 10.1097/00002030-200012010-00008 . PMID   11125887. S2CID   12747999.
• Read JA, Winter VJ, Eszes CM, Sessions RB, Brady RL (May 2001). "Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase". Proteins. 43 (2): 175–85. doi:10.1002/1097-0134(20010501)43:2<175::AID-PROT1029>3.0.CO;2-#. PMID   11276087. S2CID   196599144.
• Sung JH, Shin SA, Park HK, Montelaro RC, Chong YH (October 2001). "Protective effect of glutathione in HIV-1 lytic peptide 1-induced cell death in human neuronal cells". Journal of NeuroVirology. 7 (5): 454–65. doi:10.1080/135502801753170318. PMID   11582518. S2CID   12958486.
• Pioli PA, Hamilton BJ, Connolly JE, Brewer G, Rigby WF (September 2002). "Lactate dehydrogenase is an AU-rich element-binding protein that directly interacts with AUF1". Journal of Biological Chemistry. 277 (38): 35738–45. doi: 10.1074/jbc.M204002200 . PMID   12107167.

External links

• Overview of all the structural information available in the PDB for UniProt : P00338 (Human L-lactate dehydrogenase A chain) at the PDBe-KB .