Recombinant Human ACADS protein

**Background of ACADM Recombinant Protein**

ACADM (acyl-CoA dehydrogenase medium chain) is a mitochondrial enzyme critical in fatty acid β-oxidation, catalyzing the dehydrogenation of medium-chain acyl-CoA derivatives to generate energy. Mutations in the *ACADM* gene cause medium-chain acyl-CoA dehydrogenase deficiency (MCADD), an autosomal recessive disorder characterized by impaired fatty acid metabolism, leading to hypoglycemia, liver dysfunction, and life-threatening metabolic crises if untreated.

Recombinant ACADM protein is produced via genetic engineering, typically using expression systems like *E. coli*, yeast, or mammalian cells. Its production enables detailed study of ACADM’s structure, function, and interaction with substrates or inhibitors. Researchers employ it to model MCADD pathogenesis, screen potential therapeutics, and develop enzyme replacement strategies.

The recombinant protein retains enzymatic activity when purified, allowing kinetic assays to assess mutations’ effects on catalytic efficiency. It also aids in generating antibodies for diagnostic kits and validating gene therapy outcomes. Furthermore, structural studies using recombinant ACADM provide insights into mutation-induced conformational changes, guiding drug design.

Advances in recombinant technology, such as codon optimization and fusion tags, enhance protein yield and stability. ACADM recombinant tools are pivotal in bridging biochemical research with clinical applications, offering hope for improved diagnostics, neonatal screening, and targeted therapies for MCADD.

ACADS (acyl-CoA dehydrogenase short-chain), also known as SCAD, is a mitochondrial enzyme critical in fatty acid β-oxidation. It catalyzes the initial step of dehydrogenation for short-chain acyl-CoA substrates (C4-C6), converting them to trans-2-enoyl-CoA while transferring electrons to the electron transfer flavoprotein (ETF). This process is essential for energy production, particularly during fasting or prolonged exercise when fatty acids become a primary energy source. The ACADS gene is located on chromosome 12 (12q22) and encodes a 412-amino-acid protein that forms a homotetrameric structure.

Recombinant ACADS proteins are engineered using expression systems like E. coli or mammalian cells to study enzyme function, structure, and mutations. These proteins enable detailed biochemical characterization, including substrate specificity and kinetic parameters. Over 60 pathogenic variants in ACADS have been linked to SCAD deficiency, an autosomal recessive disorder characterized by impaired fatty acid oxidation. Symptoms range from asymptomatic metabolic markers (ethylmalonic aciduria) to severe neuromuscular manifestations in rare cases.

The production of recombinant ACADS has advanced diagnostic methods and therapeutic research. It supports enzyme replacement therapy (ERT) studies and high-throughput screening for pharmacological chaperones to stabilize misfolded variants. Structural studies using recombinant ACADS (via X-ray crystallography and cryo-EM) have revealed key catalytic residues and mechanisms of disease-causing mutations. Challenges remain in optimizing recombinant protein stability and mimicking native post-translational modifications. Current applications extend to developing cellular models for metabolic disease research and evaluating gene therapy vectors targeting mitochondrial enzymes.