AMD1 Human

AMD1 is a protein-coding gene located on chromosome 6 (6q21-q22) in humans . The enzyme plays a pivotal role in cellular growth and proliferation by regulating the levels of polyamines, which are implicated in various cellular processes, including DNA, RNA, and protein synthesis . Unlike many amino acid decarboxylases, AMD1 uses a covalently bound pyruvate residue as a cofactor rather than the more common pyridoxal 5’-phosphate .

The active enzyme is generated through post-translational autocatalytic cleavage of a precursor protein. This cleavage produces the pyruvate precursor from an internal serine residue, resulting in the formation of two non-identical subunits termed alpha and beta, which together form the active enzyme . The enzyme’s activity is essential for the biosynthesis of spermidine and spermine from putrescine, which are critical for cellular growth under most conditions .

Polyamines such as spermidine and spermine are low-molecular-weight aliphatic amines that are essential for cellular proliferation and tumor promotion . AMD1 is crucial for maintaining the levels of these polyamines, thereby promoting the maintenance and self-renewal of embryonic stem cells . Dysregulation of AMD1 has been associated with various diseases, including developmental and epileptic encephalopathy and sleeping sickness .

Human recombinant AMD1 is produced using recombinant DNA technology, which involves inserting the human AMD1 gene into a suitable expression system, such as bacteria or yeast, to produce the enzyme in large quantities. This recombinant enzyme is used in various research applications to study its structure, function, and role in polyamine biosynthesis.

Understanding the structure and function of AMD1 is crucial for developing therapeutic strategies targeting polyamine metabolism in various diseases, including cancer. Inhibitors of AMD1 are being explored as potential therapeutic agents to regulate polyamine levels and inhibit tumor growth .