Lactate dehydrogenase A (LDHA) is an enzyme which in humans is encoded by the LDHAgene.[1] It is a monomer of lactate dehydrogenase, which exists as a tetramer. The other main subunit is lactate dehydrogenase B (LDHB).
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.[2]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
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Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[8][15] Twenty seven tests were carried out on mutant mice and five significant abnormalities were observed.[8] Few homozygousmutant 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.[8]
LDHA
The following compounds have been demonstrated to inhibit the LDHA enzyme:
↑ 8.08.18.28.3Gerdin 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.
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. PMID1445373.
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. doi:10.1016/S0006-291X(05)81177-5. PMID1953713.
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. PMID1959923.
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. PMID3838278.
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. PMID7908613.
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. PMID8125298.
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. PMID8327147.
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. PMID9373149.
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. PMID10508479.
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. PMID10897012.
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. PMID11125887.
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. PMID11582518.
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. PMID12107167.
