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Download Alkaloids • Introduction and Importance to Humans = small organic
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• Alkaloids Introduction and Importance to Humans = small organic molecules (secondary metabolites) of plants which contain nitrogen (ussually in a ring) -‐ alkaloids are pharmaceutically significant -‐ traditional and modern uses (25%/75% of drugs) -‐ neurological effects, role of nitrogen -‐ potent toxins and defenses -‐ chemical ecology and co-‐evolution with insects -‐ many human physiological effects and uses Quinine (Cinchona officinalis) -‐ antibiotics (anti-‐malarial) Morphine (Papaver somniferum -‐ painkiller (analgesic) Taxol -‐ (Taxus brevifolia) -‐ anticancer drug Vinblastine (Catharanthus roseus) -‐ anticancer drug Coniine (Conium maculatum) -‐ toxin Nicotine (Nicotiana tabacum) -‐ insecticide, stimulant Atropine (Atropa belladonna) -‐ dilate pupils Cocaine (Erythroxylon coca) -‐ Caffeine (Coffea arabica) -‐ stimulant Tubocurarine (Chondodenron tomentosum) -‐ muscle relaxant -‐ examples of mechanism of action: -‐ block neuroreceptors (morphine, codeine) -‐ block reuptake of neuroreceptor (cocaine-‐dopamine) -‐ disrupt cytoskeleton -‐ tubulin (taxol) -‐ mimic neurotransmitter action (nicotine-‐acetylcholine) -‐ block signaling (cAMP phosphodiesterase -‐ caffeine) • Features and Characteristics -‐ N makes them basic in solution -‐ structurally diverse: 12,000+ structures -‐ 20% of all plant species have alkaloids -‐ concentrated in specific plant taxa (families, genera, species), but scattered around the plant kingdom -‐ biosynthetically diverse (different amino acids) -‐ strong biological effects (see ecological examples) 2 • Alkaloid Families and General Rules for Biosynthesis -‐ families classified by ring structure -‐ derived from amino acids [exception: purine alkaloids] Key amino acid for alkaloid synthesis: tyrosine -‐-‐> morphine, codeine (poppy alkaloids) tryptophan -‐-‐> quinine (quinoline alkaloids) vinblastine (indole alkaloids) glutamate (via ornithine) -‐-‐> cocaine (tropane alkaloids) -‐-‐ > nicotine (tobacco alkaloids) -‐-‐ > senecionine (pyrrollizidine alkaloids) aspartate -‐> nicotine (other portion) xanthine (from purine nucleotide synthesis) -‐> caffeine, theobromine (purine alkaloids) -‐ also: protoalkaloids (N not in ring) & pseudoalkaloids (N added later) -‐ non-‐protein amino acids can be toxic, but are not alkaloids 3 General features of alkaloid biosynthesis: -‐ many biosynthetic steps are required -‐> complex structures -‐ any one plant accumulates a mix of related alkaloids -‐ usually begins with decarboxylation (eg) tyr -‐> tyramine -‐ central intermediate can give rise to different final products: (i.e. -‐ strictosidine for the diverse quinoline alkaloids -‐ reticuline, for isoquinoline and poppy alkaloids) -‐ organ specific synthesis / storage (bark, roots, flowers) -‐ often in cell specific synthesis / storage (latex ducts and laticifers (poppy alkaloids), epidermis (Vinca alkaloids), idioblasts) Example 1 -‐ Localization of enzymes for poppy alkaloids in roots, phloem parenchyma, laticifers, and idioblasts: Example 2 -‐ Case study of dimeric monoterpene indole terpenoid alkaloids (MIAs) from Vinca -‐ sequestered within cells and special structures -‐ biosynthesis of components in different cell types (phloem parenchyma, epidermis, idioblasts (see Roepke et al. PNAS 107 p.15291 (2010): -‐ distribution of catharanthine in epidermis, and potential of dimeric subunit linkages during wounding and defense reactions 4
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