MDH1 Human

MDH1 is composed of two main domains: an N-terminal NAD binding domain and a C-terminal substrate binding domain. It functions as a homodimer, meaning it forms a complex with another identical MDH1 molecule . The primary function of MDH1 is to catalyze the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system. This reaction is a key step in the citric acid cycle (also known as the Krebs cycle), which is essential for energy production in cells .

MDH1 is involved in several metabolic processes, including glycolysis and the urea cycle. It also plays a pivotal role in the malate-aspartate shuttle, which facilitates the transfer of reducing equivalents across the mitochondrial membrane, thereby linking the metabolic activities of the cytosol and mitochondria .

MDH1 expression is amplified in various cancers, such as lung squamous cell carcinoma, diffuse B cell lymphoma, bladder cancer, and pancreatic cancer. Higher expression levels of MDH1 are often negatively correlated with patient survival, making it a potential biomarker for cancer prognosis . Additionally, MDH1 supports increased rates of cancer glycolysis by serving as both a carbon and NAD supplier, in lieu of and in addition to lactate dehydrogenase (LDH) .

The activity of MDH1 is regulated through various post-translational modifications. For instance, acetylation of MDH1 activates its enzymatic activity and enhances intracellular levels of NADPH, promoting adipogenic differentiation . Conversely, methylation on arginine 248 (R248) negatively regulates MDH1 by disrupting its dimerization, thereby repressing mitochondrial respiration and inhibiting glutamine utilization .

Recombinant MDH1 refers to the enzyme produced through recombinant DNA technology, which allows for the expression of the human MDH1 gene in a host organism, such as bacteria or yeast. This technology enables the production of large quantities of MDH1 for research and therapeutic purposes .