Tyrosine depletion in metazoan proteins was recently explained to be due to the appearance of tyrosine kinases in Metazoa. Here, we present a complementary explanation for the depletion of tyrosine, stating the importance of tyrosine in signaling not only as a phosphorylation target but also as a precursor for catecholamines and hormones. Molecules (dopamine, norepinephrine, and epinephrine, and to a lesser extent serotonin and melatonin) critical to metazoan multicellular signaling are also greatly dependent on a supply of tyrosine. These signaling molecules are synthesized in two highly linked pathways specific to metazoans. In addition, the shikimate pathway that non-metazoans use to synthesize the aromatic amino acids is not present in metazoans. These important pathway changes have occurred between Metazoa and other eukaryotes, causing significant changes to tyrosine metabolism and rendering tyrosine crucial for extracellular signaling. In addition, the evolutionary and functional linkage between these two pathways and the resulting implications for neuropathology are discussed.