LDHA
Lactate dehydrogenase A, also known as LDHA, is an enzyme which in humans is encoded by the LDHA gene.[1]
Function
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]
Glycolysis and Gluconeogenesis edit
- ↑ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".
Model organisms
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Abnormal |
| Recessive lethal study | Abnormal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Abnormal[3] |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Abnormal[4] |
| Plasma immunoglobulins | Normal |
| Haematology | Abnormal[5] |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Tail epidermis wholemount | Normal |
| Skin Histopathology | Normal |
| Brain histopathology | Normal |
| Salmonella infection | Normal[6] |
| Citrobacter infection | Normal[7] |
| All tests and analysis from[8][9] |
Model organisms have been used in the study of LDHA function. A conditional knockout mouse line, called Ldhatm1a(EUCOMM)Wtsi[10][11] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[12][13][14]
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 homozygous mutant 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]
References
- ↑ Chung FZ, Tsujibo H, Bhattacharyya U, Sharief FS, Li SS (November 1985). "Genomic organization of human lactate dehydrogenase-A gene". Biochem. J. 231 (3): 537–41. PMC 1152784. PMID 3000353.
- ↑ "Entrez Gene: LDHA lactate dehydrogenase A".
- ↑ "Glucose tolerance test data for Ldha". Wellcome Trust Sanger Institute.
- ↑ "Clinical chemistry data for Ldha". Wellcome Trust Sanger Institute.
- ↑ "Haematology data for Ldha". Wellcome Trust Sanger Institute.
- ↑ "Salmonella infection data for Ldha". Wellcome Trust Sanger Institute.
- ↑ "Citrobacter infection data for Ldha". Wellcome Trust Sanger Institute.
- 1 2 3 4 Gerdin 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.
- ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ↑ "International Knockout Mouse Consortium".
- ↑ "Mouse Genome Informatics".
- ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ↑ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
Further reading
- Miyajima H, Shimizu T, Kaneko E (1993). "[Gene expression in lactate dehydrogenase-A subunit deficiency]". Rinsho Shinkeigaku 32 (10): 1087–92. PMID 1297552.
- Sudo K, Maekawa M, Shioya M, Ikeda K, Takahashi N, Isogai Y, Li SS, Kanno T, Machida K, Toriumi J (1992). "Molecular analysis of genetic mutation in electrophoretic variant of human lactate dehydrogenase-A(M) subunit". Biochem. Int. 27 (6): 1051–7. PMID 1445373.
- Maekawa M, Sudo K, Li SS, Kanno T (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". Biochem. Biophys. Res. Commun. 180 (2): 1083–1090. doi:10.1016/S0006-291X(05)81177-5. PMID 1953713.
- Maekawa M, Sudo K, Li SS, Kanno T (1992). "Genotypic analysis of families with lactate dehydrogenase A (M) deficiency by selective DNA amplification". Hum. Genet. 88 (1): 34–38. doi:10.1007/BF00204925. PMID 1959923.
- Scrable HJ, Johnson DK, Rinchik EM, Cavenee WK (1990). "Rhabdomyosarcoma-associated locus and MYOD1 are syntenic but separate loci on the short arm of human chromosome 11". Proc. Natl. Acad. Sci. U.S.A. 87 (6): 2182–2186. doi:10.1073/pnas.87.6.2182. PMC 53650. PMID 2315312.
- Maekawa M, Sudo K, Kanno T, Li SS (1990). "Molecular characterization of genetic mutation in human lactate dehydrogenase-A (M) deficiency". Biochem. Biophys. Res. Commun. 168 (2): 677–682. doi:10.1016/0006-291X(90)92374-9. PMID 2334430.
- Gosti F, Marty MC, Courvalin JC, Maunoury R, Bornens M (1987). "Centrosomal proteins and lactate dehydrogenase possess a common epitope in human cell lines". Proc. Natl. Acad. Sci. U.S.A. 84 (4): 1000–1004. doi:10.1073/pnas.84.4.1000. PMC 304349. PMID 2434947.
- Chung FZ, Tsujibo H, Bhattacharyya U, Sharief FS, Li SS (1986). "Genomic organization of human lactate dehydrogenase-A gene". Biochem. J. 231 (3): 537–41. PMC 1152784. PMID 3000353.
- Tsujibo H, Tiano HF, Li SS (1985). "Nucleotide sequences of the cDNA and an intronless pseudogene for human lactate dehydrogenase-A isozyme". Eur. J. Biochem. 147 (1): 9–15. doi:10.1111/j.1432-1033.1985.tb08711.x. PMID 3838278.
- Glass RD, Doyle D (1972). "Genetic control of lactate dehydrogenase expression in mammalian tissues". Science 176 (4031): 180–181. doi:10.1126/science.176.4031.180. PMID 5014440.
- Maekawa M, Sudo K, Kobayashi A, Sugiyama E, Li SS, Kanno T (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". Clin. Chem. 40 (4): 665–8. PMID 7908613.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Miyajima H, Takahashi Y, Suzuki M, Shimizu T, Kaneko E (1993). "Molecular characterization of gene expression in human lactate dehydrogenase-A deficiency". Neurology 43 (7): 1414–9. doi:10.1212/wnl.43.7.1414. PMID 8327147.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, Gure AO, Jäger D, Jäger E, Knuth A, Chen YT, Old LJ (1999). "Antigens recognized by autologous antibody in patients with renal-cell carcinoma". Int. J. Cancer 83 (4): 456–464. doi:10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5. PMID 10508479.
- Vilà MR, Nicolás A, Morote J, de I, Meseguer A (2000). "Increased glyceraldehyde-3-phosphate dehydrogenase expression in renal cell carcinoma identified by RNA-based, arbitrarily primed polymerase chain reaction". Cancer 89 (1): 152–164. doi:10.1002/1097-0142(20000701)89:1<152::AID-CNCR20>3.0.CO;2-T. PMID 10897012.
- Boutet A, Altmeyer R, Héry C, Tardieu M (2001). "Direct role of plasma membrane-expressed gp120/41 in toxicity to human astrocytes induced by HIV-1-infected macrophages". AIDS 14 (17): 2687–2697. doi:10.1097/00002030-200012010-00008. PMID 11125887.
- Read JA, Winter VJ, Eszes CM, Sessions RB, Brady RL (2001). "Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase". Proteins 43 (2): 175–185. doi:10.1002/1097-0134(20010501)43:2<175::AID-PROT1029>3.0.CO;2-#. PMID 11276087.
- Sung JH, Shin SA, Park HK, Montelaro RC, Chong YH (2001). "Protective effect of glutathione in HIV-1 lytic peptide 1-induced cell death in human neuronal cells". J. Neurovirol. 7 (5): 454–465. doi:10.1080/135502801753170318. PMID 11582518.
- Pioli PA, Hamilton BJ, Connolly JE, Brewer G, Rigby WF (2002). "Lactate dehydrogenase is an AU-rich element-binding protein that directly interacts with AUF1". J. Biol. Chem. 277 (38): 35738–35745. doi:10.1074/jbc.M204002200. PMID 12107167.
| |||||||||||||
This article is issued from Wikipedia - version of the Tuesday, September 15, 2015. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.