MDH1
Description
The MDH1 (malate dehydrogenase 1) is a protein-coding gene located on chromosome 2.
MDH1, the gene encoding malate dehydrogenase, cytoplasmic, is responsible for the reversible conversion of malate to oxaloacetate using NAD/NADH as a cofactor in the citric acid cycle. The enzyme is located in the cytoplasm and plays a key role in the malate-aspartate shuttle, coordinating metabolism between the cytosol and mitochondria. Different isoforms of the protein are produced by alternative splicing. Acetylation of MDH1 enhances its enzymatic activity and increases NADPH levels, promoting adipogenic differentiation. Methylation at arginine 248 (R248) negatively regulates MDH1 activity. PRMT4 (CARM1) methylates and inhibits MDH1 by disrupting its dimerization, repressing mitochondrial respiration and glutamine utilization. This methylation also reduces cellular NADPH levels, increasing susceptibility to oxidative stress, and suppressing cell growth and clonogenic activity.
MDH1 catalyzes the reduction of aromatic alpha-keto acids using NADH as a cofactor (PubMed:2449162, PubMed:3052244). It plays vital roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, contributing to mitochondrial NADH supply for oxidative phosphorylation (PubMed:31538237). MDH1 can reduce 2-oxoglutarate to 2-hydroxyglutarate, leading to increased reactive oxygen species (ROS) (PubMed:34012073).
MDH1 is also known as DEE88, EIEE88, HEL-S-32, KAR, MDH-s, MDHA, MGC:1375, MOR2.
