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Gene Review

LDHC  -  lactate dehydrogenase C

Homo sapiens

Synonyms: CT32, Cancer/testis antigen 32, L-lactate dehydrogenase C chain, LDH testis subunit, LDH-C, ...
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Disease relevance of LDHC

  • LDHC protein is a biomarker of obstructive (OA) and non-obstructive (NOA) azoospermia in seminal plasma [1], [2].
  • Expression of LDHC in tumors is neither mediated by gene promotor demethylation, as previously described for other germ cell-specific genes activated in cancer, nor induced by hypoxia as demonstrated for enzymes of the glycolytic pathway [3].
  • Some tumors like meningiomas showed a midzone pattern like increased LDH3 [4].
  • In summary, LDH3 activity was elevated in the oliguric stage of Korean hemorrhagic fever and LDH2 was elevated in chronic renal failure; those values were correlated with the BUN level [5].
  • LDH 3 was decreased during late pregnancy but increased in severe pre-eclampsia [6].
  • Thus, in NHL, LDH-3 seems to be a reliable marker of the presence of the disease in any case, whereas S-LDH is more related to the spread of the lymphoma [7].

Psychiatry related information on LDHC

  • Total LDH and isoenzyme LDH-1 were significantly higher, whereas the fractions of LDH-2 and LDH-3 were significantly lower in CJD patients [8].

High impact information on LDHC

  • At least two gene duplication events have led to the three lactate dehydrogenase (LDH; EC isozymes (LDH-A, LDH-B, and LDH-C) of chordates [9].
  • Sequence analysis of teleost retina-specific lactate dehydrogenase C: evolutionary implications for the vertebrate lactate dehydrogenase gene family [9].
  • On the basis of amino acid sequence similarity, we conclude that the LDH-C isozymes in fish and mammals are not orthologous but derive from independent gene duplications [9].
  • The sequence and structure of human testis-specific L-lactate dehydrogenase [LDHC4, LDHX; (L)-lactate: NAD+ oxidoreductase, EC] has been derived from analysis of a complementary DNA (cDNA) clone comprising the complete protein coding region of the enzyme [10].
  • Moreover, we discovered aberrant splicing of LDHC restricted to cancer cells, resulting in four novel tumor-specific variants displaying structural alterations of the catalytic domain [3].

Chemical compound and disease context of LDHC

  • LDH-X, an isoenzyme of lactate dehydrogenase specific for germinal epithelium activity, has been measured in the seminal plasma of infertile subjects whose infertility had different origins [11].
  • Lactate dehydrogenase (EC isoenzyme LDH-C4 (LDH-X) has been analyzed quantitatively in semen from men with different fertility status, such as men with pregnant wives, men with primary or secondary infertility, volunteers, men taking salazopyrine and men exposed to very hot baths [12].
  • The standard semen parameters (sperm concentration and motility and Kruger morphology) and total sperm creatine kinase, HspA2, LDH, and LDH-X activities, and MDA levels were assessed in the control and varicocele groups [13].

Biological context of LDHC


Anatomical context of LDHC


Associations of LDHC with chemical compounds

  • LDHC represents the first lactate dehydrogenase isoform with restriction to tumor cells [3].
  • The presence of this element could be involved in regulating ldh-c through the glucocorticoid/androgen pathways at the early stages of ldh-c expression [18].
  • The distribution of LDH isozymes in the fetal vitreous and lens homogenate and the near-term neonate aqueous as determined by polyacrylamide disc electrophoresis, was similar to that of the fetal aqueous, LDH-1 and LDH-5 being least and LDH-3 and LDH-4, the highest [19].
  • We have analyzed the catalytic properties and subcellular distribution of the lactate dehydrogenase isozyme specific for testis and sperm (LDH X or C4) [20].
  • Thiophenoxyacetate, levamisole and dimethyl sulfoxide depressed total LDH and LDH-X was the principal component in the respective patterns for ejaculate concentrates [21].

Other interactions of LDHC

  • Locus determining the human sperm-specific lactate dehydrogenase, LDHC, is syntenic with LDHA [14].
  • Studies of pigeon LDH have shown tight linkage between LDHB and LDHC leading to the expectation that these genes would be syntenic in man [14].
  • TPTE, LDHC, SPO11 were expressed neither in tumor samples nor in healthy tissue [22].
  • 1) The Sp1 transcription factor is a testis-"enriched" protein that is absent from most somatic tissues and that appears to play a major role in determining ldh-c expression in the testis [18].
  • The UEV3 gene is located on chromosome 11 closely adjacent to TSG101 and LDH-C [23].

Analytical, diagnostic and therapeutic context of LDHC

  • Here, we used a combination of gel retardation assays and an in vitro transcription system derived from human tissues to better define the elements that govern ldh-c transcription [18].
  • Mean total LDH activity in the CSF was 34.62 +/- 6.52 U/l. Patients with infantile spasms had a lower LDH-1 percentage and higher LDH-3 percentage; the differences from the control group were statistically significant (p < 0.01) [24].
  • This was in marked contrast to the LDH isoenzyme pattern observed in the lavage effluent, which showed a lower percent LDH1 and LDH2 and a higher percent LDH3, LDH4, and LDH5 when compared with the corresponding prelavage isoenzyme percentages for serum (unpaired t test, p less than 0.001) [25].
  • Human isoenzyme LDH-X (lactate dehydrogenase isoenzyme X) was isolated from seminal fluid of frozen semen samples by affinity chromatography by using oxamate-Sepharose and AMP-Sepharose [26].
  • Serum and tumor tissue of a patient with neuroblastoma contained an abnormal isoenzyme of lactate dehydrogenase (LDH; EC, which, on agarose gel electrophoresis, migrated between LDH-2 and LDH-3 with a mobility the same as that of the extra LDH isoenzyme found in normal human erythrocytes [27].


  1. Differential Diagnosis of Azoospermia with Proteomic Biomarkers ECM1 and TEX101 Quantified in Seminal Plasma. Drabovich, A.P., Dimitromanolakis, A., Saraon, P., Soosaipillai, A., Batruch, I., Mullen, B., Jarvi, K., Diamandis, E.P. Sci. Transl. Med. (2013) [Pubmed]
  2. Verification of male infertility biomarkers in seminal plasma by multiplex selected reaction monitoring assay. Drabovich, A.P., Jarvi, K., Diamandis, E.P. Mol. Cell. Proteomics. (2011) [Pubmed]
  3. Multiple splice variants of lactate dehydrogenase C selectively expressed in human cancer. Koslowski, M., Türeci, O., Bell, C., Krause, P., Lehr, H.A., Brunner, J., Seitz, G., Nestle, F.O., Huber, C., Sahin, U. Cancer Res. (2002) [Pubmed]
  4. Changes in lactate dehydrogenase isoenzyme pattern in patients with tumors of the central nervous system. Subhash, M.N., Rao, B.S., Shankar, S.K. Neurochem. Int. (1993) [Pubmed]
  5. Changes of lactate dehydrogenase and its isoenzyme activity in renal diseases. Kang, S.K., Ha, C.Y., Cho, K.H., Park, S.K., Kim, U.H. Nephron (1991) [Pubmed]
  6. Serum lactic acid dehydrogenase and isoenzymes during pregnancy and labor. Makkonen, M., Penttilä, I.M., Castrén, O. Acta obstetricia et gynecologica Scandinavica. (1980) [Pubmed]
  7. Serum lactate dehydrogenase isoenzyme pattern in non-Hodgkin's lymphomas. Ricerca, B.M., Storti, S., Campisi, S., Pagano, L., Dalla Torre, F., Marra, R., Amato, A., Mango, G., Bizzi, B. Int. J. Biol. Markers (1988) [Pubmed]
  8. 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]
  9. 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]
  10. Epitopes of human testis-specific lactate dehydrogenase deduced from a cDNA sequence. Millan, J.L., Driscoll, C.E., LeVan, K.M., Goldberg, E. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  11. Measurement of seminal LDH-X and transferrin in normal and infertile men. Orlando, C., Casano, R., Caldini, A.L., Forti, G., Barni, T., Bonfanti, L., Serio, M. J. Androl. (1988) [Pubmed]
  12. LDH-C4 in human seminal plasma and its relationship to testicular function. II. Clinical aspects. Eliasson, R., Virji, N. Int. J. Androl. (1985) [Pubmed]
  13. Effect of varicocelectomy on sperm creatine kinase, HspA2 chaperone protein (creatine kinase-M type), LDH, LDH-X, and lipid peroxidation product levels in infertile men with varicocele. Yeşilli, C., Mungan, G., Seçkiner, I., Akduman, B., Açikgöz, S., Altan, K., Mungan, A. Urology (2005) [Pubmed]
  14. 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]
  15. Human testis-specific lactate dehydrogenase-C promoter drives overexpression of mouse lactate dehydrogenase-1 cDNA in testes of transgenic mice. Markert, C.L., Amet, T.M., Goldberg, E. J. Exp. Zool. (1998) [Pubmed]
  16. Human testicular lactate dehydrogenase-C gene is interrupted by six introns at positions homologous to those of LDH-A (muscle) and LDH-B (heart) genes. Takano, T., Li, S.S. Biochem. Biophys. Res. Commun. (1989) [Pubmed]
  17. Testis-specific lactate dehydrogenase (LDH-C4; Ldh3) in murine oocytes and preimplantation embryos. Coonrod, S., Vitale, A., Duan, C., Bristol-Gould, S., Herr, J., Goldberg, E. J. Androl. (2006) [Pubmed]
  18. Deoxyribonucleic acid-protein interactions and expression of the human testis-specific lactate dehydrogenase promoter: transcription factor Sp1 plays a major role. Bonny, C., Cooker, L.A., Goldberg, E. Biol. Reprod. (1998) [Pubmed]
  19. Glycolytic enzymes of human fetal and neonatal intraocular fluids. Gershbein, L.L. Curr. Eye Res. (1985) [Pubmed]
  20. On the functional significance of LDH X. Blanco, A. The Johns Hopkins medical journal. (1980) [Pubmed]
  21. Polyacrylamide disc electrophoresis of human semen lactate dehydrogenase in the presence of sulfur compounds. Gershbein, L.L. Res. Commun. Chem. Pathol. Pharmacol. (1984) [Pubmed]
  22. Expression of cancer-testis antigens as possible targets for antigen-specific immunotherapy in head and neck squamous cell carcinoma. Atanackovic, D., Blum, I., Cao, Y., Wenzel, S., Bartels, K., Faltz, C., Hossfeld, D.K., Hegewisch-Becker, S., Bokemeyer, C., Leuwer, R. Cancer Biol. Ther. (2006) [Pubmed]
  23. Identification and characterization of UEV3, a human cDNA with similarities to inactive E2 ubiquitin-conjugating enzymes. Kloor, M., Bork, P., Duwe, A., Klaes, R., von Knebel Doeberitz, M., Ridder, R. Biochim. Biophys. Acta (2002) [Pubmed]
  24. Lactic dehydrogenase isoenzyme in cerebrospinal fluid of children with infantile spasms. Nussinovitch, M., Harel, D., Eidlitz-Markus, T., Amir, J., Volovitz, B. Eur. Neurol. (2003) [Pubmed]
  25. Serum and lavage lactate dehydrogenase isoenzymes in pulmonary alveolar proteinosis. Hoffman, R.M., Rogers, R.M. Am. Rev. Respir. Dis. (1991) [Pubmed]
  26. Isolation of human lactate dehydrogenase isoenzyme X by affinity chromatography. Kolk, A.H., van Kuyk, L., Boettcher, B. Biochem. J. (1978) [Pubmed]
  27. Abnormal lactate dehydrogenase isoenzyme in serum and tumor tissue of a patient with neuroblastoma. Otsu, N., Hirata, M., Miyazawa, K., Tuboi, S. Clin. Chem. (1985) [Pubmed]
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