Neotropical Pharmacy

1. Neotropical Pharmacy Secondary Metabolites for Plant Defense Katie Williams

2. Q & A • What are the three main groups of Secondary Metabolites? • What are the four determinates of toxicity for plant defense? • What are the main characteristics of each regarding plant defense? • What is the term specific to the decrease in latitude resulting in an increase of plants bearing alkaloids? • What are the two main types of drainage rivers (regarding nutrient retention) and in which do you find ‘SM-rich’ or ‘SM-poor’ Plants?

3. Why do plants need extra defense? • Plants are “sitting ducks” for herbivores. • They constitute over 99% of all living mass in tropical rainforests (~900 metric tons per hectare). • Leaf damage severely affects plant ecology. • Competition living space.

4. Secondary Metabolites? Primary Metabolites (PMs) The universal compounds found in all plants: the known sugars, protein amino acids, purines, purimidiness of nucleic acids, chlorophylls, etc. Secondary Metabolites (SMs) All other plant chemicals that vary in plant species and also do not appear to have an essential role in metabolism: Alkaloids, terpenoids, phenolics, etc. Origin Secondary Metabolites are said to have first been a photosynthetic byproduct or chemical waste, proving ‘fit’ those plants creating them. Then evolution did its stuff....

5. Classification Choices 1) According to carbon skeletal type. This was found to be “far too cumbersome for practical use.” 2) According to biogenesis or biosynthetic origin. This is the most widely used system of SM classification. Using a biosynthetic classification system, largest groups of Secondary Metabolites: Terpenoids Alkaloids and other nitrogen compounds Phenolics

6. Terpenoids Terpenoids (isoprenoids) • Common biosynthic origin from isopentenule and dimethyulallyl purophosphates • generally lipophilic, plant oils • leaf glandular trichomes, bud exudates, bark resins • Flavonoids, aromatics, carotenoids, chlorophylls • May mimic insect growth hormones • Include Cardiac Glycosides which affect the heart. • Toxic to most fungi and insects

7. Alkaloids • Best known nitrogen-containing Metabolites • Low content offset by biological potency • Found in 20% angiosperms • Most familiar and addictive. Cocaine, morphine, THC, caffeine, nicotine • insecticide • Bitter tasting, affect cell membrane function, cause difficulties in digestion. Generally affect Nervous system.

8. Phenolics • Common biosythetic origin from phenylalanine • Aromatic • Ionize in presence of a base • Used in spices • Tannins are used in tanning leather

9. SMs and Herbivory Scenarios: • Herbivore does not taste chemicals, eats them, and dies, for example, if it ate an alkaloid-rich plant. • Herbivore eats small portion of plant and suffers from ‘unpleasant symptoms’ afterwards. Most vertebrates can associate the two events and learn to avoid that plant. • Herbivore does not feed on a single plant but feeds on many different species. Using this approach, the herbivore avoids ingestion of high levels of one kind of chemical. • Herbivore is adapted to on a particular plant species (food specialist) and is immune to affects of chemical. Also, many species of insect use plant chemicals to their advantage.

10. Defense

11. SMs and HerbivoryHow Herbivores Survive Such a Toxic HELL Common in insects, known poisonous butterflies

12. Alkaloid Content and Specialist- Aphids • Aphids and phloem • Sweet lupins vs. Toxic lupins • Specialized aphid, Macrosiphum Albifrons, sequestration * * * * * * * * M.Wink et al (1992)

13. What determines high levels of toxicity? Latitude (Tropical vs. Temperate) Availability of Nutrients Rates of succession Age of Plant Tissue

14. Latitudinal Trends Latitudinal Cline Decrease in latitude results in an increase of plants bearing alkaloids. Why? Potency

15. Tropical vs. TemperateAlkaloid Content Kricher: 27% 45%

16. Nutrients • Expensive Leaf Production Areas: • Blackwater River draining areas • Whitewater River draining areas Black water forest stream, called an Igarape

17. Succession Rates Toxicity and Young Leaves • Young leaves are a target for herbivory; understandably high levels of defense compounds • Toxicity depends on species • Alternative defense: delayed greening, low nutrient composition, rapid leaf expansion • Trade off: • Fast Growing vs. Defense • Gap specialists

18. Rates of Herbivory Comparison of rates of herbivory in temperate and tropical forests. Annual Mature LvesYoung Lves Young/total % n %/d n %/d n % n Temperate7.1 13 27.0 Tropical wet forest Shade-tolerant sp.11.1 21 .03 105 .71 150 68.3 31 Gap specialists48.0 4 .18 37 .65 37 47.3 30 Tropical dry forest14.2 4 .07 78 .15 61 28.7 62 Annual is the average percentage damage per year, with N being the number of studies (each study included many species). Daily rates of herbivory are presented for young and mature leaves (%/d), young/total indicates the percentage of the total lifetime damage that occurs while leaves are expanding, n indicates the number of species. Data on young/total from the temperate zone are the average for an entire forest. Data taken from Coley et al. 1996. (http://ecolsys.annualreviews.org/cgi/content/full/27/1/305/T1)

19. SMs and People • Taxol/Paclitaxel • A chemical discovered in the pacific Yew Tree is now the first drug of choice in several tumorous cancers including Breast Candcer. • According to The National Cancer Society, Tropical Forests could ccontain 20 ‘superstar’ drugs Anticancer drugs. • Of the 150 most commonly prescribed drugs in the United States, 57% contain at least one major active compound derived from compounds in nature. • While 25% of all Western Pharmaceuticals are derived from rainforest ingredients, less than 1% of these tropical tress and plants have been tested by scientists • The U.S. National Cancer Institute has identified 3000 plants that are active against cancer cells. • Vinblastine • A chemical discovered in the Madagascar Periwinkle . First drug of choice in many forms of Leukemia and has increased survival rate of childhood leukemia by 80%

20. Q & A • What are the three main groups of Secondary Metabolites? • Terpenoids • Alkaloids • Phenolics • What are the main characteristics of each regarding plant defense? • Terpenoids are generally plant oils including flavinoids and aromatics • Alkaloids are known for their tendency to affect the nervous system, tasting bitter • Phenolics, including tannins, are generally toxic to insects due to their tendency to be acidic • What are the four determinates of toxicity for plant defense? • Latitude • Availability of nutrients • Age of Plant tissue • Rates of succession • What is the term specific to the decrease in latitude resulting in an increase of plants bearing alkaloids? • Latitudinal Cline • What are the two main types of drainage rivers (regarding nutrient retention) and in which do you find ‘SM-rich’ or ‘SM-poor’ Plants? • Blackwater rivers, known for nutrient leaching resulting in Highly defended plants but low rates of growth. • Whitewater rivers, low levels of nutrient leaching but high sediment erosion, resulting in poorly defended plants but high rates of growth

21. Sources • Coley, P. D., Barone, J. A..1996. Herbivory and Plant Defenses in Tropical Forests. Annu. Rev. Ecol. Syst.. 27:305-335 • Harborne, J.B. 1999. Classes and Functions of Secondary Products FromPlants. Chemicals From Plants. Ed. NJ Walton, De Brown. ICP: London. 1-26 • Kricher, J., 1997. A Neotropical Companion. Princeton University Press • Levin, Donald. 1976. Alkaloid-Bearing Plants: An Ecogeographic Perspective. Am. Nat. 110: 261-284 • Novacek, M.J., 2001. TheBiodiversity Crisis. NP: N.Y, 1-20 • Verpoorte, R. 2000. Plant Secondary Metabolism. Metabolic Engineering of Plant Secondary Metabolism. Ed. Verpoorte, R., Alferman, A.W.. Kluwer Academic Publishers. 1-29 • Wink, M.. 1998. Functions of Plant Secondary Metabolites and Their Exploitation in Biotechnology. Sheffield Academic Press: England. 1-19, 110 • Smolenski et al. 1972, 1973, 1974a, 1974b. unpublished data taken from: Levin, D., 1976. Alkaloid-Bearing Plants: An Ecogeographic Perspective. Am. Nat. 110: 261-284 Medicinal Facts found on www.rain-tree.com/plantdrugs.htm Photo of blackwater stream found at:http://www.amazonian-fish.co.uk/indexc40.html