# Origin and Function of Structural Diversity in the Plant Specialized Metabolome
## 2 The Four Major Specialized Metabolome Pathways
### Alkaloids  
Alkaloids are characterized by great structural diversity and physiological properties. The sole thing that alkaloids have in common is the presence of a nitrogen atom, mostly present in a heterocyclic ring. This nitrogen atom in alkaloids originates mainly from amino acids, and, in general, the carbon skeleton of the particular amino acid is incorporated in the alkaloid structure, hence, classification is based on their biosynthesis precursor [45]. However, some alkaloid classes derive only their nitrogen atom from an amino acid via a transamination reaction, while the remainder of the structure is derived from, e.g., acetate, shikimate, terpenoids or steroids; these are classified as pseudoalkaloids [45]. Most alkaloids are derived from ornithine (derived from glutamic acid in plants), arginine, lysine, tyrosine and tryptophan. Furthermore, minor alkaloid classes are produced from histidine (imidazole alkaloids), nicotinic acid (pyridine alkaloids), anthranilic acid (quinazoline alkaloids) and xanthosine (purine alkaloids) [45]. Polyamines, e.g., agmatine, putrescine and spermidine, are formed from either ornithine or arginine [46]. Polyamines derived from ornithine yield pyrrolidines and tropanes (e.g., cocaine) upon cyclization, whereas cyclization of arginine-derived polyamines yields pyrrolidines (Figure 3[45]). Having one additional methylene moiety as compared to ornithine, lysine enters alkaloid biosynthesis pathways that are characterized by similar cyclization mechanisms as those observed for polyamine-derived alkaloids; they lead to the piperidines (six-ring) and quinolizidines (two fused six-rings) rather than the pyrrolidines (five-ring) and pyrrolizidines (two fused five-rings). A third class derived from lysine, the indolizidines, is characterized by a six-ring fused to a five-ring [45]. Similar biosynthetic reaction mechanisms are also observed for the alkaloid classes derived from tyrosine and tryptophan. Decarboxylation of tyrosine and tryptophan leads to the phenylethylamines (e.g., Nordenine) and the indolics (e.g., tryptamine). Schiff base formation with a short-chain aliphatic aldehyde/ketone followed by ring closure converts the phenylethylamines and the indolics to the tetrahydrooisquinolines and the \(\beta\)-carbolines, respectively. When Schiff base formation couples a phenylethylamine with a C\({}_{6}\)C\({}_{2}\) aldehyde, such as phenylacetaldehyde, the benzyltetrahydrodioxquinolines (e.g., reticuline) are produced, whereas coupling with a dihydro C\({}_{6}\)C\({}_{3}\) aldehyde (e.g., 4-hydroxydihydrocinnamaldehyde) or with secologanin produces the phenethylisoquinolines and the terpenoid tetrahydrooisquinone-lines, respectively. Schiff base formation between indolics and secologanin yields the terpenoid indole alkaloids (e.g., strictosidine). Oxidative radical-radical coupling between the two phenolic moieties present in the structures of benzyltetrahydrodioxquinolines and phenethylisoquinolines results in different skeleton types, i.e., the morphinan type (e.g., morphine) and the aporphine type, respectively. Another skeleton type, i.e., the protobberberine type (for example, berberine), is formed from benzyltetrahydrodioxquinolines via a second Schiff base formation. Other alkaloid classes that are derived from tryptophan are the quinolines, pyrrolquinolines, pyrrololodes and the ergot alkaloids [45]. Within plants, alkaloids are believed to serve as a storage form of nitrogen and as protection against herbivory [47]. When a pathogen or predator attacks a plant, the alkaloid can interfere with the predator's protein synthesis, with the predator's enzyme activity and/or with the predator's nervous system [48]. In addition, by inhibiting the growth of competing plants, alkaloids can act as an herbicide [49]. The bioactivity of the alkaloids is due to the presence of the nitrogen atom; the lone pair electrons on the nitrogen can act as proton-acceptors, whereas the hydrogen-atoms in primary and secondary amines can act as a proton-donor.