Lactate dehydrogenase A (LDHA) is an enzyme which in humans is encoded by the LDHA gene. [5] It is a monomer of Lactate dehydrogenase, which exists as a tetramer. The other main subunit is lactate dehydrogenase B (LDHB).
Lactate dehydrogenase A (LDHA) is an enzyme which in humans is encoded by the LDHA gene. [5] It is a monomer of Lactate dehydrogenase, which exists as a tetramer. The other main subunit is lactate dehydrogenase B (LDHB).
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 tumors, 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. [6]
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
| 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 [7] |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Abnormal [8] |
| Plasma immunoglobulins | Normal |
| Haematology | Abnormal [9] |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Tail epidermis wholemount | Normal |
| Skin Histopathology | Normal |
| Brain histopathology | Normal |
| Salmonella infection | Normal [10] |
| Citrobacter infection | Normal [11] |
| All tests and analysis from [12] [13] |
Model organisms have been used in the study of LDHA function. A conditional knockout mouse line, called Ldhatm1a(EUCOMM)Wtsi [14] [15] 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. [16] [17] [18]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. [12] [19] Twenty seven tests were carried out on mutant mice and five significant abnormalities were observed. [12] 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. [12]
The following compounds have been demonstrated to inhibit the LDHA enzyme:
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Chromodomain-helicase-DNA-binding protein 7 also known as ATP-dependent helicase CHD7 is an enzyme that in humans is encoded by the CHD7 gene.
The sodium/glucose cotransporter 2 (SGLT2) is a protein that in humans is encoded by the SLC5A2 gene.
Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of pyruvate to lactate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that transfers a hydride from one molecule to another.
Glutamate—cysteine ligase catalytic subunit is an enzyme that in humans is encoded by the GCLC gene.
Histone-lysine N-methyltransferase SETDB1 is an enzyme that in humans is encoded by the SETDB1 gene. SETDB1 is also known as KMT1E or H3K9 methyltransferase ESET.
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AT rich interactive domain 4A (RBP1-like), also known as ARID4A, is a protein which in humans is encoded by the ARID4A gene.
Leucine-rich repeats and immunoglobulin-like domains protein 1 is a protein that in humans is encoded by the LRIG1 gene. It encodes a transmembrane protein that has been shown to interact with receptor tyrosine kinases of the EGFR family and with MET and RET.
SET and MYND (myeloid-Nervy-DEAF-1) domain-containing protein 3 is a protein that in humans is encoded by the SMYD3 gene.
Spermine synthase is an enzyme that in humans is encoded by the SMS gene. The protein encoded by this gene belongs to the spermidine/spermine synthases family. This gene encodes a ubiquitous enzyme of polyamine metabolism.
Lysine-specific demethylase 4C is an enzyme that in humans is encoded by the KDM4C gene.
Protein Jumonji is a protein that in humans is encoded by the JARID2 gene. JARID2 is a member of the alpha-ketoglutarate-dependent hydroxylase superfamily.
ATP synthase mitochondrial F1 complex assembly factor 2 is an enzyme that in humans is encoded by the ATPAF2 gene.
Aldehyde dehydrogenase 3 family, member B1 also known as ALDH3B1 is an enzyme that in humans is encoded by the ALDH3B1 gene.
Ubiquinone biosynthesis protein COQ9, mitochondrial, also known as coenzyme Q9 homolog (COQ9), is a protein that in humans is encoded by the COQ9 gene.
Cytokine receptor-like factor 3 is a protein that in humans is encoded by the CRLF3 gene.
Retinol dehydrogenase 16 (all-trans) is a protein that in humans is encoded by the RDH16 gene. The gene is also known as RODH-4 and SDR9C8.
Chromobox homolog 7 is a protein that in humans is encoded by the CBX7 gene. The loss of CBX7 gene expression has been shown to correlate with a malignant form of thyroid cancer.
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