Mescaline - Biosynthesis of Mescaline

Biosynthesis of Mescaline

Mescaline can be synthesized from tyrosine or a hydroxylated phenylalanine. In Lophophora williamsii, dopamine converts into mescaline in a biosynthetic pathway involving m-O-methylation and aromatic hydroxylation.

Tyrosine and phenylalanine serve as the metabolic precursors to synthesis of mescaline. Tyrosine can undergo either a decarboxylation via Tyrosine Decarboxylase to generate Tyramine and subsequently undergo an oxidation at carbon 3 by a Monophenol Hydroxylase or first be hydroxylated by Tyrosine Hydroxylase to form L-DOPA and decarboxylated by DOPA Decarboxylase. These create dopamine which then experiences methylation by a catechol-O-methyltransferase, or COMT, by a SAM dependent mechanism. The resulting intermediate is then oxidized again by a hydroxylase enzyme, likely Monophenol Hydroxylase again, at carbon 5, and methylated by COMT. The product, methylated at the two meta positions with respect to the alkyl substituent, experiences a final methylation at the 4 carbon by a Guaiacol-O-methyltransferase which also operates by a SAM dependent mechanism. This final methylation step results in the production of mescaline. Phenylalanine serves as a precursor by first being converted to L-Tyrosine by L-amino acid hydroxylase. Once converted, it follows the same pathway as described above.