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Gene Review

LDHB  -  lactate dehydrogenase B

Homo sapiens

Synonyms: HEL-S-281, L-lactate dehydrogenase B chain, LDH heart subunit, LDH-B, LDH-H, ...
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Disease relevance of LDHB


High impact information on LDHB

  • Physiological basis for swimming endurance differences between LDH-B genotypes of Fundulus heteroclitus [6].
  • At 25 degrees C there were no differences between LDH-B phenotypes in erythrocyte adenosine triphosphate levels, blood oxygen affinity, or swimming performance [6].
  • Since oxygen delivery to muscle affects swimming performance, fish of each homozygous LDH-B phenotype were swum to exhaustion at 10 degrees or 25 degrees C to determine whether in vitro differences attributed to the LDH-B allelic isozymes were manifest in vivo [6].
  • Adaptive variation in lactate dehydrogenase-B gene expression: role of a stress-responsive regulatory element [7].
  • To test the hypothesis that this element is involved in the variation between populations of F. heteroclitus, we exposed transiently transgenic fish containing Ldh-B regulatory sequence/reporter gene constructs to handling stress or injected cortisol [7].

Biological context of LDHB


Anatomical context of LDHB

  • LDHA and LDHB are expressed in most somatic tissues, while expression of LDHC is confined to the germinal epithelium of the testes [8].
  • In contrast, LDH-A and LDH-B were ubiquitously expressed in normal and tumor tissues, with LDH-B levels considerably lower and heterogeneous in normal samples compared to those expressed in tumor cell lines [13].
  • This interpretation was confirmed by a decreased concentration of the LDH-B subunit in lactate dehydrogenase isozymes of the patient's fibroblasts, consistent with his being hemizygous for the LDHB locus [14].
  • In lymphocyte cultures 9% of the cells had either no or two rings, but the patient's RBC had normal activities of the enzymes lactate dehydrogenase B and peptidase B, whose loci are located on the proximal portions of 12p and 12q, respectively [15].
  • Approximately one third of the Ldh-B proximal promoter contains interspersed regions that are functionally important: (1) they bind transcription factors in vivo, (2) they effect a change in transcription as assayed by transient transfection into two different fish cell lines, and (3) they bind purified transcription factors in vitro [16].

Associations of LDHB with chemical compounds


Physical interactions of LDHB


Regulatory relationships of LDHB

  • 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 [22].
  • Contrary to this, in PBMC of NHL patients prior to therapy TNF-alpha induced a significant decrease ( p<0.05) of LDH-H isotype activity [23].

Other interactions of LDHB


Analytical, diagnostic and therapeutic context of LDHB

  • The predicted sequence of 333 amino acid residues was confirmed by amino acid composition and/or sequence analyses of a total of 185 (56%) residues from tryptic peptides of human LDH-B protein [12].
  • These findings were indicative of a partial LDH-B subunit deficiency, which was confirmed in erythrocyte hemolysates by Western blotting [20].
  • Immunohistochemistry showed a higher frequency of LDHB expression in benign or non-malignant tissues, 59/ 73 (81%), compared to cancer cases, 3/53 (6%) (P < 0.001) [2].
  • 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 [23].
  • Consistent with observed variation in Ldh-B transcription rate between populations, significant differences in reporter gene activity were driven by flanking regions from northern and southern populations both in cell culture and in vivo [27].


  1. Lactic dehydrogenase isozyme patterns and alpha-hydroxybutyrate dehydrogenase activities in serum from newborns, patients with ovarian cancer or myocardial infarction. Kikuchi, Y., Kita, T., Furuya, K., Kato, K. Cancer Biochem. Biophys. (1988) [Pubmed]
  2. Lactate dehydrogenase-B is silenced by promoter hypermethylation in human prostate cancer. Leiblich, A., Cross, S.S., Catto, J.W., Phillips, J.T., Leung, H.Y., Hamdy, F.C., Rehman, I. Oncogene (2006) [Pubmed]
  3. Expression of the copy DNA for human A4 and B4 L-lactate dehydrogenases in Escherichia coli. Barstow, D.A., Black, G.W., Sharman, A.F., Scawen, M.D., Atkinson, T., Li, S.S., Chia, W.N., Clarke, A.R., Holbrook, J.J. Biochim. Biophys. Acta (1990) [Pubmed]
  4. Structure and sequence conservation of a putative hypoxia response element in the lactate dehydrogenase-B gene of Fundulus. Rees, B.B., Bowman, J.A., Schulte, P.M. Biol. Bull. (2001) [Pubmed]
  5. Usefulness of two independent histopathological classifications of tumor regression in patients with rectal cancer submitted to hyperfractionated pre-operative radiotherapy. Liszka, L., Zielinska-Pajak, E., Pajak, J., Golka, D., Starzewski, J., Lorenc, Z. World J. Gastroenterol. (2007) [Pubmed]
  6. Physiological basis for swimming endurance differences between LDH-B genotypes of Fundulus heteroclitus. DiMichele, L., Powers, D.A. Science (1982) [Pubmed]
  7. Adaptive variation in lactate dehydrogenase-B gene expression: role of a stress-responsive regulatory element. Schulte, P.M., Glemet, H.C., Fiebig, A.A., Powers, D.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  8. 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]
  9. 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]
  10. Identification of the origin of a 22p+ chromosome by triplex dosage effect of LDH B, GAPHD, TPI and ENO2. Dallapiccola, B., Brinchi, V., Magnani, M., Dacha, M. Ann. Genet. (1980) [Pubmed]
  11. Sequence analysis of teleost retina-specific lactate dehydrogenase C: evolutionary implications for the vertebrate lactate dehydrogenase gene family. Quattro, J.M., Woods, H.A., Powers, D.A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  12. The cDNA and protein sequences of human lactate dehydrogenase B. Sakai, I., Sharief, F.S., Pan, Y.C., Li, S.S. Biochem. J. (1987) [Pubmed]
  13. 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]
  14. Resolution of breakpoints in a complex rearrangement by use of multiple staining techniques: confirmation of suspected 12p12.3 intraband by deletion dosage effect of LDHB. Magenis, E., Brown, M.G., Chamberlin, J., Donlon, T., Hepburn, D., Lamvik, N., Lovrien, E., Yoshitomi, M. Am. J. Med. Genet. (1981) [Pubmed]
  15. Ring chromosome and latent centromeres. Zuffardi, O., Danesino, C., Poloni, L., Pavesi, F., Bianchi, C., Gargantini, L. Cytogenet. Cell Genet. (1980) [Pubmed]
  16. Evolutionary analysis of TATA-less proximal promoter function. Crawford, D.L., Segal, J.A., Barnett, J.L. Mol. Biol. Evol. (1999) [Pubmed]
  17. Arginine to tryptophan substitution in the active site of a human lactate dehydrogenase variant--LDHB GUA1: postulated effects on subunit structure and catalysis. Shonnard, G.C., Hud, N.V., Mohrenweiser, H.W. Biochim. Biophys. Acta (1996) [Pubmed]
  18. 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]
  19. Detection and characterization of new genetic mutations in individuals heterozygous for lactate dehydrogenase-B(H) deficiency using DNA conformation polymorphism analysis and silver staining. Maekawa, M., Sudo, K., Kitajima, M., Matsuura, Y., Li, S.S., Kanno, T. Hum. Genet. (1993) [Pubmed]
  20. A novel missense mutation in human lactate dehydrogenase B-subunit gene. Takatani, T., Takaoka, N., Tatsumi, M., Kawamoto, H., Okuno, Y., Morita, K., Masutani, T., Murakawa, K., Okamoto, Y. Mol. Genet. Metab. (2001) [Pubmed]
  21. Functional analyses of natural variation in Sp1 binding sites of a TATA-less promoter. Segal, J.A., Barnett, J.L., Crawford, D.L. J. Mol. Evol. (1999) [Pubmed]
  22. 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]
  23. 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]
  24. Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2-p12.1. Rodriguez, S., Jafer, O., Goker, H., Summersgill, B.M., Zafarana, G., Gillis, A.J., van Gurp, R.J., Oosterhuis, J.W., Lu, Y.J., Huddart, R., Cooper, C.S., Clark, J., Looijenga, L.H., Shipley, J.M. Oncogene (2003) [Pubmed]
  25. A genetic study of various enzyme polymorphisms in Pleurodeles waltlii (Urodele amphibian). I. Lactate dehydrogenase-B and glucose-6-phosphate dehydrogenase. Gasser, F., Ferrier, V., Jaylet, A., Deparis, P. Biochem. Genet. (1983) [Pubmed]
  26. Regional mapping of TPI, LDH-B, and Pep-B on chromosome 12 of man. Jongsma, A.P., Hagemeijer, A., Meera Khan, P. Cytogenet. Cell Genet. (1975) [Pubmed]
  27. Structural and functional differences in the promoter and 5' flanking region of Ldh-B within and between populations of the teleost Fundulus heteroclitus. Schulte, P.M., Gómez-Chiarri, M., Powers, D.A. Genetics (1997) [Pubmed]
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