Mimosine's mechanism is pyridoxal-phosphate independent

Mimosine is a toxic plant amino acid and a structural analog of both pyridoxal-phosphate (PLP) and tyrosine (figure 1) (1). Mimosine has been described as an effective inhibitor of DNA replication in mammalian cells (2). Several mechanisms nave been proposed to explain mimosine's inhibitory effects; but none have been reliably confirmed. Our research disproves one of the current theories that mimosine acts as an inhibitor of serine hydroxymethyltransferase (SHMT) and thereby inhibits purine nucleotide biosynthesis in mammalian cells. Mimosine has been shown to decrease purine nucleotide pools in Chinese Hamster Ovary (CHO) cells, and this has been suggested to be the primary inhibitory effect of mimosine on mammalian cells. It has been suggested that mimosine limits SHMT activity, a PLP-dependent enzyme that is critical for the synthesis of DNA precursors, and this in turn results in the depletion of cellular deoxyribonucleotide purine pools. The results of this study indicate that while mimosine does inhibit human MCF-7 cell proliferation, it does not deplete purine or pyrimidine deoxyribonucleotide pools in MCF-7 cells. Mimosine's effects appear PLP independent with respect to SHMT inhibition.