plant alkaloids their functions and biosynthesis

plank alkaloids

1. Plant Alkaloids and their biosynthesis Isabella Bs biochem

2. Definition first mentioned in 1819 by W. Meißner , an apothecary from Halle. He observed that these compounds appeared “like alkali”, and so named them alkaloids Alkaloids are low-molecular weight, nitrogenous specialized metabolites occurring in approximately 20% of plant species. alkaloids are a special group of chemicals that are active at different cellular levels of organisms, and they take part in the biological processes of plants, animals and microorganisms Many of the about 12,000 structurally elucidated alkaloids show potent biological activity

3. Alkaloids comprise a variety of heterocyclic secondary metabolite Alkaloids belong to a group of secondary metabolites that are synthesized from amino acids and contain one or several N atoms as constituents of heterocycles. Many of these alkaloids act as defense substances against animals and microorganisms Since alkaloids usually are bases, they are stored in the protonated form, mostly in the vacuole, which is acidic. Since ancient times humans have used alkaloids in the form of plant extracts as poisons, stimulants, and narcotics, and, last but not least, as medicine.

4. Types of alkaloids Alkaloids can be classified in the terms of their (1) biological and ecological activity; (2) chemical structures and (3) biosynthetic pathway. From the point of view of biological activity it is possible to divide alkaloids into (1) neutral or weakly basic molecules (e.g., lactams such as ricinine , certain N-oxides such as indicine ), (2) animal-derived alkaloids (e.g., anuran, mammalian and arthropod alkaloids), (3) marine alkaloids, (4) moss alkaloids, (5) fungal and bacterial alkaloids and (6) non-natural alkaloids (structurally modified or analogues).

5. True alkaloids True alkaloids derive from amino acid and they share a heterocyclic ring with nitrogen. These alkaloids are highly reactive substances with biological activity even in low doses. All true alkaloids have a bitter taste and appear as a white solid, with the exception of nicotine which has a brown liquid. True alkaloids form water-soluble salts. Moreover, most of them are well-defined crystalline substances which unite with acids to form salts. True alkaloids may occur in plants (1) in the free state, (2) as salts and (3) as N-oxides.

6. Usambarensine : An example of a true alkaloid.

7. Mescaline: An example of protoalkaloids

8. The devil’s-pepper genus contains l-tryptophan-derived alkaloids. Rauwolfia serpentina appears on flowers l-tryptophan with its aromatic side chain is a precursor of indole, terpenoid indole, quinoline , pyrroloindole and ergot alkaloids.

9. In 1806 the pharmacy assistant Friedrich Wilhelm Sertürner isolated morphine from poppy seeds. Another 146 years had to pass before the structure of morphine was finally resolved in 1952. More than 10,000 alkaloids of very different structures are now known. Their synthesis pathways are very diverse, to a large extent still not known

10. Figure shows a small selection of important alkaloids. Alkaloids are classified according to their heterocycles. Coniine, a piperidine alkaloid, is a very potent poison in hemlock. Socrates died when he was forced to drink this poison

11. Nicotine Nicotine, which also is very toxic, contains a pyridine and a pyrrolidine ring. It is formed in the roots of tobacco plants and is carried along with the xylem sap into the stems and leaves. Nicotine sulfate, a byproduct of the tobacco industry, is used as a very potent insecticide (e.g., for fumigating greenhouses). No insect is known to be resistant to nicotine.

12. Cocaine,the well-known narcotic,contains tropaneas a heterocycle,in which the N atom is a constituent of two rings. A further well-known tropane alkaloid is atropine a poison contained in deadly nightshade ( Atropa belladonna). In low doses, it dilates the pupils of the eye and is therefore used in medicine for eye examination. Cleopatra allegedly used extracts containing atropine to dilate her pupils to appear more attractive

13. Quinine,a quinoline alkaloid from the bark of Chinchuna officinalis growing in South America, was known by the Spanish conquerors to be an antimalarial drug. The isoquinoline alkaloid morphineis an important painkiller and is also a precursor for the synthesis of heroin. Caffeine, the stimulant of coffee, contains a purine as the heterocycle.

14. In the search for new medicines, large numbers of plants are being analyzed for their content of secondary metabolites. As a result of a systematic search, the alkaloid taxol , isolated from the yew tree Taxus brevifolia , is now used for cancer treatment. Derivatives of the alkaloid camptothezine from the Chinese “happy tree” Camptotheca acuminata are also being clinically tested as cancer therapeutics. The search for new medicines against malaria and viral infections continues. Since large quantities of pharmacologically interesting substances often cannot be gained from plants, attempts are being made with the aid of genetic engineering either to increase production by the corresponding plants or to transfer the plant genes into microorganisms in order to use the latter for production.

15. Biosynthesis of alkaloids

16. three general examples of the synthesis of alkaloids from amino acids: (1) synthesis of the pyrroline ring and derived alkaloids from ornithine; (2) synthesis of the piperidine ring and derived alkaloids from lysine and (3) synthesis of isoquinolizidine alkaloids from tyrosine.

17. There are only four basic active blocks for the secondary compounds Acetyl coenzyme A (acetyl CoA) is used in the acetate pathway, and shikimic acid in the shikimate pathway. The third block, mevalonic acid, is active in the mevalonate pathway, and the last, 1-deoxyxylulose 5-phosphate, key to the deoxyxylulose phosphate pathway

18. Alkaloid biosynthesis needs the substrate The synthesis of alkaloids starts from the acetate, shikimate, mevalonate and deoxyxylulose pathways. The acetyl coenzyme A pathway (acetate pathway) is the source of some alkaloids and their precursors (e.g., piperidine alkaloids or anthranilic acid as aromatized CoA ester ( antraniloyl -CoA)). Shikimic acid is a product of the glycolytic and pentose phosphate pathways, a construction facilitated by parts of phosphoenolpyruvate and erythrose 4-phosphate. The shikimic acid pathway is the source of such alkaloids as quinazoline , quinoline and acridine .

19. The mevalonate pathway is based on mevalonic acid (three molecules of acetyl-CoA) which is closely related to the acetate pathway, while the deoxyxylulose phosphate pathway is based on a combination of pyruvic acid and glyceraldehyde 3-phosphate (both from the glycolytic pathway). Together, mevalonate and deoxyxylulose phosphate pathways produce terpenoid and steroid compounds.

20. Nicotiana tabacum Tobacco ( Nicotiana tabacum ) is one of those species, and it has become an economically important crop plant because of alkaloid production, although the entire  Nicotiana  genus is recognized for producing these type of metabolites The alkaloids found in Nicotiana plants are toxic compounds that play a major role in defense against generalist herbivores The root represents the main site of alkaloid synthesis in Nicotiana species After their production, the alkaloids are transported through the xylem and accumulated in leaves, which are the areas more susceptible to herbivore attacks

21. Regarding its ecological importance, alkaloid biosynthesis is a complex process that involves several enzymatic steps Nicotine has two ring moieties, a pyrrolidine ring and a pyridine ring, derived from two branch pathways The pyridine ring of nicotine is derived from nicotinic acid, whereas the pyrrolidine ring originates from polyamine putrescine metabolism, which is gradually modified to N- methylpyrrolinium

22. Nicotine biosynthesis in a root cortical cell of Nicotiana . Nicotine biosynthesis in a root cortical cell of Nicotiana . Enzymes are indicated in red letters. AO , aspartate oxidase; QS, quinolinic acid synthase; Gly-3-P, glyceraldehyde-3-P; QPT , quinolinate phosphoribosyltransferase ; ADC, arginine decarboxylase; ODC, ornithine decarboxylase; AIH, agmatine iminohydrolase ; CPA , N- carbamoylputrescine amidohydrolase ; PMT, putrescine N methyltransferase; MPO, N- methylputrescine oxidase ; BBL, berberine bridge enzyme-like; MATE1/2, multidrug and toxic compound extrusion 1 and 2; NUP1, nicotine uptake permease 1; ???: undefined step.

23. Nicotine produced in the Nicotiana root cells is translocated through the xylem to the leaves, where it can be demethylated to nornicotine . Nornicotine , by the action of an acyltransferase, is acylated to N- acylnornicotine ( NacNN ) in the trichomes . NacNN is secreted by the glandular trichome , and acts in the antiherbivory defense. ER, endoplasmic reticulum.

24. References Singh A. and D.P. Isabel. 2015. BIOSYNTHESIS OF AMARYLLIDACEAE ALKALOIDS: A BIOCHEMICAL OUTLOOK. Alkaloids. ISBN: 978-1-63482-074-5 Zenkner et a; BIOSYNTHESIS IN NICOTIANA: A METABOLIC OVERVIEW. Tobacco Science (2019) 56:1–9. Hotti.H . and H. Rischer . The killer of Socrates: Coniine and Related Alkaloids in the Plant Kingdom. Molecules  2017, 22(11), 1962;  https://doi.org/10.3390/molecules22111962 Jan et al., 2012. Plant tropane alkaloid biosynthesis evolved independently in the Solanaceae and Erythroxylaceae . 10304–10309. PNAS. vol. 109 no. 26