De novo biosynthesis of morphine in animal cells: an evidence-based model

Recent empirical findings have contributed valuable mechanistic information in support of a regulated de novo biosynthetic pathway for chemically authentic morphine in animal cells, with many similarities to the extensively characterized multi-enzyme plant pathway in opium poppy (Papaver somniferum). The present review elaborates an evidence-based model of cellular morphine expression that reflects a coalescence of these recent biochemical data with historical data gleaned from over thirty years of neurochemical/neuropharmacological investigation into the etiology and biological significance of dopamine (DA)-related heterocyclic conjugate molecules, termed tetrahydroisoquinoline (TIQ) or benzylisoquinoline (BIQ) alkaloids, and with outstanding work completed over the last decade that has elucidated biochemical and molecular bases of morphine and related isoquinoline alkaloid expression in plant systems. In essence, we are now afforded a rare window of opportunity to firmly establish essential biochemical linkages between plant and animal biosynthetic pathways that have been conserved throughout evolution.