LDHA (Lactate Dehydrogenase A)
The LDHA gene encodes the A subunit, which is also often called M subunit, of lactate dehydrogenase, an enzyme which catalyzes the interconversion of pyruvate to lactate and NADH to NAD+. This enzyme was first reported as having five isozymes in 1959, where it was also shown that they were tissue-specific (Markert and Moller 1959). Tsujibo and cols first described the nucleotide sequence of the human LDHA in 1984, and its predicted amino acid sequence showed 92% homology with pig LDHA (Tsujibo et al. 1985). In 2001, Read and cols determined the crystal structure of the two main LDH isoforms, which provided evidence for the hypothesis that the different activity of the isoforms is likely to be due to the variation of charged residues peripheral to the active site, since both isoforms have very similar crystal structures (Read et al. 2001).
- Fan J, Hitosugi T, Chung TW, Xie J, Ge Q, Gu TL, Polakiewicz RD, Chen GZ, Boggon TJ, Lonial S, Khuri FR, Kang S, Chen J. Tyrosine phosphorylation of lactate dehydrogenase A is important for NADH/NAD(+) redox homeostasis in cancer cells. Mol Cell Biol. 2011;31:4938–50. doi:10.1128/MCB.06120-11.CrossRefPubMedPubMedCentralGoogle Scholar
- Maekawa M, Shinji K, Sudo K, Kanno T. Estimation of the gene frequency of lactate dehydrogenase subunit deficiencies. Am J Hum Genet. 1984;1204–14.Google Scholar
- Read JA, Winter VJ, Eszes CM, Sessions RB, Brady RL, Ldh L. Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase 2001;185:175–85.Google Scholar