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LDHA  -  lactate dehydrogenase A

Homo sapiens

 
 
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Disease relevance of LDHA

 

Psychiatry related information on LDHA

  • Association of an exonic LDHA polymorphism with altered respiratory response in probands at high risk for panic disorder [6].
  • Total LDH and isoenzyme LDH-1 were significantly higher, whereas the fractions of LDH-2 and LDH-3 were significantly lower in CJD patients [7].
 

High impact information on LDHA

  • Here we report the observation of reactions of individual molecules of lactate dehydrogenase (LDH-1), which produces NADH from lactate and nicotinamide adenine dinucleotide (NAD+) [8].
  • Therefore, new CK-MB or LDH1 elevations associated with arrhythmias must result from myocardial damage to DC cardioversion [9].
  • To determine whether DC cardioversion affects these serum enzyme levels, we recorded total CK, total LDH, CK-MB, and LDH1 levels serially during 24 hours following elective DC cardioversion in 18 patients without cardiac ischemia [9].
  • Ectopic expression of LDH-A alone in Rat1a fibroblasts was sufficient to induce apoptosis with glucose deprivation but not with serum withdrawal, suggesting that LDH-A mediates the unique apoptotic effect of c-Myc when glycolysis is blocked [10].
  • The lactate dehydrogenase A (LDH-A) gene, whose product participates in normal anaerobic glycolysis and is frequently increased in human cancers, has been identified as a c-Myc-responsive gene [10].
 

Chemical compound and disease context of LDHA

  • Using a transcription system from nuclear extracts of rat C6 glioma cells we have investigated the mechanism by which transcription from the lactate dehydrogenase A subunit (LDH) promoter is regulated via the cAMP-activated pathway [11].
  • Increases in Ldh1 mRNA and LDH activity were not correlated with lactic acid production, which was maximal at the onset of anoxia in unacclimated roots and then declined [12].
  • Serum malondialdehyde-like material (MDA-LM), as an index of lipid peroxidation, and the serum enzymes CK, CK-MB, LDH, LDH1 and, alpha-HBDH were evaluated in a group of 26 patients with acute myocardial infarction (AMI), seven with angina pectoris (AP), and in a normal control group of 94 subjects [13].
  • Total lactate dehydrogenase and LDH-1 are supplemental to creatine kinase (CK) and CK-MB, while aspartate aminotransferase may be omitted in the diagnosis of myocardial infarction [14].
  • Jaundice with increased indirect bilirubin, anemia with reticulocytosis, elevated plasma hemoglobin concentration and predominance of LDH1 were indicative of hemolysis [15].
 

Biological context of LDHA

 

Anatomical context of LDHA

 

Associations of LDHA with chemical compounds

  • Locus determining the human sperm-specific lactate dehydrogenase, LDHC, is syntenic with LDHA [16].
  • The following loci could not be localized with full confidence: LDHA, NP, PEPD, ITP, and PGK [22].
  • For the oxidation of glyoxylate, K(M) values were 0.18 mM and 0.26 mM for LDHA and LDHB respectively with NAD+ as cofactor [23].
  • Neither LDHA nor LDHB utilised glycolate as substrate and NADPH was a poor cofactor with a relative activity less than 3% that of NADH [23].
  • A combination of different indicators, such as opposite changes in LDH and alpha-glycerophosphate dehydrogenase activity, coupled with elevated proportions of LDH-M, may be used to diagnose neoplasia most reliably [24].
 

Physical interactions of LDHA

  • The possible biochemical role of the tyrosylphosphorylated LDH-A complexed with ras p21 in cell transformation and progression of human ovarian cancer is worthy of further investigation [25].
  • Herein we review current findings indicating that the c-Myc oncogenic transcription factor and hypoxia-inducible factor 1 (HIF-1) are able to bind the lactate dehydrogenase A promoter cis acting elements, which resemble the core carbohydrate response element (ChoRE), CACGTG [26].
 

Regulatory relationships of LDHA

  • CONCLUSIONS: The somatic LDHA in R51 cells is transcriptionally silenced by promoter hypermethylation around exon a, leaving only LDHB to be expressed normally and a testis-specific variant transcript of LDHA containing exon 0 [3].
  • In patients after administration of chemotherapy, TNF-alpha in a dose of 100 U/ml induced a significant increase ( p<0.05) of LDH-M isotype activity, but not of LDH-H [27].
 

Other interactions of LDHA

  • Conserved canonical E boxes in ENO1, HK2, and LDHA occur in 31- to 111-bp islands with high interspecies sequence identity (>65%) [28].
  • LD2ex possibly results from tetramerization of three wild-type LDHB molecules and one variant LDHA product [3].
  • The difficulties observed for LDHA and VIL1 are probably due to the fact that these genes belong to large gene families and therefore suggest that they may not be the most appropriate markers for a standardisation effort [29].
  • The Km values and specificity constants (Kcat/K(M)) of purified recombinant human LDHA, LDHB and GRHPR were determined for the reduction of glyoxylate and hydroxypyruvate [23].
  • Southern and protein analysis of LDHA and ALB provided identical segregation data [30].
 

Analytical, diagnostic and therapeutic context of LDHA

References

  1. Rhabdomyosarcoma-associated locus and MYOD1 are syntenic but separate loci on the short arm of human chromosome 11. Scrable, H.J., Johnson, D.K., Rinchik, E.M., Cavenee, W.K. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  2. Involvement of PLAGL2 in activation of iron deficient- and hypoxia-induced gene expression in mouse cell lines. Furukawa, T., Adachi, Y., Fujisawa , J., Kambe, T., Yamaguchi-Iwai, Y., Sasaki, R., Kuwahara, J., Ikehara, S., Tokunaga, R., Taketani, S. Oncogene (2001) [Pubmed]
  3. Electrophoretic variant of a lactate dehydrogenase isoenzyme and selective promoter methylation of the LDHA gene in a human retinoblastoma cell line. Maekawa, M., Inomata, M., Sasaki, M.S., Kaneko, A., Ushiama, M., Sugano, K., Takayama, J., Kanno, T. Clin. Chem. (2002) [Pubmed]
  4. Molecular characterization of gene expression in human lactate dehydrogenase-A deficiency. Miyajima, H., Takahashi, Y., Suzuki, M., Shimizu, T., Kaneko, E. Neurology (1993) [Pubmed]
  5. Hormonal regulation of lactate dehydrogenase-A through activation of protein kinase C pathways in MCF-7 breast cancer cells. Li, X., Qin, C., Burghardt, R., Safe, S. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  6. Association of an exonic LDHA polymorphism with altered respiratory response in probands at high risk for panic disorder. Philibert, R.A., Nelson, J.J., Sandhu, H.K., Crowe, R.R., Coryell, W.H. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2003) [Pubmed]
  7. CSF lactate dehydrogenase activity in patients with Creutzfeldt-Jakob disease exceeds that in other dementias. Schmidt, H., Otto, M., Niedmann, P., Cepek, L., Schröter, A., Kretzschmar, H.A., Poser, S. Dementia and geriatric cognitive disorders. (2004) [Pubmed]
  8. Differences in the chemical reactivity of individual molecules of an enzyme. Xue, Q., Yeung, E.S. Nature (1995) [Pubmed]
  9. Direct current cardioversion. Effect on creatine kinase, lactic dehydrogenase and myocardial isoenzymes. Reiffel, J.A., Gambino, S.R., McCarthy, D.M., Leahey, E.B. JAMA (1978) [Pubmed]
  10. A unique glucose-dependent apoptotic pathway induced by c-Myc. Shim, H., Chun, Y.S., Lewis, B.C., Dang, C.V. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  11. Functional analysis of cis- and trans-regulatory elements of the lactate dehydrogenase A subunit promoter by in vitro transcription. Short, S., Short, M.L., Milkowski, D.M., Jungmann, R.A. J. Biol. Chem. (1991) [Pubmed]
  12. Differential expression of two tomato lactate dehydrogenase genes in response to oxygen deficit. Germain, V., Raymond, P., Ricard, B. Plant Mol. Biol. (1997) [Pubmed]
  13. Serum malondialdehyde-like material (MDA-LM) in acute myocardial infarction. Aznar, J., Santos, M.T., Valles, J., Sala, J. J. Clin. Pathol. (1983) [Pubmed]
  14. Lactate dehydrogenase isoenzyme 1 in the diagnosis of myocardial infarction. Fogh-Andersen, N., Sørensen, P., Møller-Petersen, J., Ring, T. J. Clin. Chem. Clin. Biochem. (1982) [Pubmed]
  15. Acute hemolysis associated with hepatitis A. Hara, K., Tagawa, K., Unuma, T. Gastroenterol. Jpn. (1985) [Pubmed]
  16. Locus determining the human sperm-specific lactate dehydrogenase, LDHC, is syntenic with LDHA. Edwards, Y.H., Povey, S., LeVan, K.M., Driscoll, C.E., Millan, J.L., Goldberg, E. Dev. Genet. (1987) [Pubmed]
  17. Mapping of human lactate dehydrogenase-A, -B, and -C genes and their related sequences: the gene for LDHC is located with that for LDHA on chromosome 11. Li, S.S., Luedemann, M., Sharief, F.S., Takano, T., Deaven, L.L. Cytogenet. Cell Genet. (1988) [Pubmed]
  18. Regional localization of the sperm-specific lactate dehydrogenase, LDHC, gene on human chromosome 11. Edwards, Y., West, L., Van Heyningen, V., Cowell, J., Goldberg, E. Ann. Hum. Genet. (1989) [Pubmed]
  19. Identification of breast cancer-restricted antigens by antibody screening of SKBR3 cDNA library using a preselected patient's serum. Forti, S., Scanlan, M.J., Invernizzi, A., Castiglioni, F., Pupa, S., Agresti, R., Fontanelli, R., Morelli, D., Old, L.J., Pupa, S.M., Ménard, S. Breast Cancer Res. Treat. (2002) [Pubmed]
  20. Genotypic analysis of families with lactate dehydrogenase A (M) deficiency by selective DNA amplification. Maekawa, M., Sudo, K., Li, S.S., Kanno, T. Hum. Genet. (1991) [Pubmed]
  21. Nucleotide sequences of the cDNA and an intronless pseudogene for human lactate dehydrogenase-A isozyme. Tsujibo, H., Tiano, H.F., Li, S.S. Eur. J. Biochem. (1985) [Pubmed]
  22. Comparative gene mapping of man and Cebus capucinus: a study of 23 enzymatic markers. Créau-Goldberg, N., Cochet, C., Turleau, C., de Grouchy, J. Cytogenet. Cell Genet. (1981) [Pubmed]
  23. A preliminary account of the properties of recombinant human Glyoxylate reductase (GRHPR), LDHA and LDHB with glyoxylate, and their potential roles in its metabolism. Mdluli, K., Booth, M.P., Brady, R.L., Rumsby, G. Biochim. Biophys. Acta (2005) [Pubmed]
  24. Enzyme activities and isozyme patterns in human lung tumors. Balinsky, D., Greengard, O., Cayanis, E., Head, J.F. Cancer Res. (1984) [Pubmed]
  25. Identification of LDH-ras p21 protein complex and expression of these genes in human ovarian cancer. Chow, S.N., Lin, J.K., Li, S.S., Chien, C.H. Gynecol. Oncol. (1997) [Pubmed]
  26. Oncogenes in tumor metabolism, tumorigenesis, and apoptosis. Dang, C.V., Lewis, B.C., Dolde, C., Dang, G., Shim, H. J. Bioenerg. Biomembr. (1997) [Pubmed]
  27. TNF-alpha induces changes in LDH isotype profile following triggering of apoptosis in PBL of non-Hodgkin's lymphomas. Jurisic, V., Bumbasirevic, V., Konjevic, G., Djuricic, B., Spuzic, I. Ann. Hematol. (2004) [Pubmed]
  28. Evaluation of myc E-box phylogenetic footprints in glycolytic genes by chromatin immunoprecipitation assays. Kim, J.W., Zeller, K.I., Wang, Y., Jegga, A.G., Aronow, B.J., O'Donnell, K.A., Dang, C.V. Mol. Cell. Biol. (2004) [Pubmed]
  29. Development and assignment of bovine-specific PCR systems for the Texas nomenclature marker genes and isolation of homologous BAC probes. Gautier, M., Laurent, P., Hayes, H., Eggen, A. Genet. Sel. Evol. (2001) [Pubmed]
  30. A new gene mapping resource: interspecies hybrids between Père David's deer (Elaphurus davidianus) and red deer (Cervus elaphus). Tate, M.L., Mathias, H.C., Fennessy, P.F., Dodds, K.G., Penty, J.M., Hill, D.F. Genetics (1995) [Pubmed]
  31. Analysis of genetic mutations in human lactate dehydrogenase-A(M) deficiency using DNA conformation polymorphism in combination with polyacrylamide gradient gel and silver staining. Maekawa, M., Sudo, K., Li, S.S., Kanno, T. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  32. Increased glyceraldehyde-3-phosphate dehydrogenase expression in renal cell carcinoma identified by RNA-based, arbitrarily primed polymerase chain reaction. Vilà, M.R., Nicolás, A., Morote, J., de, I., Meseguer, A. Cancer (2000) [Pubmed]
 
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