Pyrrolizidine alkaloids - chemistry, biosynthesis, pathway, toxicity, safety and perspectives of medicinal usage

• Autorzy: Dreger M , Stanislawska M. , Krajewska-Patan A. , Mielcarek S. , Mikolajczak P.L. , Buchwald W.

Warianty tytułu

PL

Alkaloidy pirolizydynowe - chemia, biosynteza, szlak metaboliczny, toksycznosc, bezpieczenstwo i perspektywy zastosowania w medycynie

• Języki publikacji: EN

Abstrakty

EN

Pyrrolizidine alkaloids (PAs) are the class of secondary metabolites that evolved as a powerful tool in the plant defensive interactions against herbivores. The occurrence of PAs in the plant world is scattered in several unrelated botanic families with special abundance in Asteraceae, Boraginaceae and Fabaceae. Homospermidine synthase (HSS) was recognized as a key enzyme that catalyzes homospermidine formation from polyamines. The studies of HSS kinetic and gene sequence revealed that it is of polyphyletic origin and raised as a result of deoxyhypusine synthase (DHS) gene duplication. The ability of PAs production occurred independently at least four times in course of plant evolution. The PAs biosynthesis is tightly correlated with growth phase and biomass production. It is supposed that PAs biosynthesis is individually regulated in different lineages of plants. The PAs with a 1,2 unsaturated necine skeleton show toxic activity (hepatoxicity, carcinogenicity, genotoxicity, teratogenocity and cytotoxicity). It is though that pyrrolic esters formation during the detoxication process in the liver is the main mechanism of PAs toxicity. The pyrrolic esters are highly reactive and tend to bind rapidly with nucleophilic macromolecules including DNA and DNA-protein inducing hepatotoxicity or tumorigenecity. The problem of PAs toxicity cause the restrictions in the production and sale of herbal products. This review encompasses the present status of the pyrrolizidine alkaloids in the plants studies and summarize the topics of chemistry, biosynthesis, evolution including the involved genes, the factors affecting on biosynthesis, accumulation and toxicity of PAs.

PL

Alkaloidy pirolizydynowe (PA) to metabolity wtórne, które stanowią potężną broń roślin stosowaną w reakcjach obronnych przeciwko roślinożercom. Występują w kilkunastu nie spokrewnionych ze sobą rodzinach botanicznych, szczególnie często wśród przedstawicieli Asteraceae, Boraginaceae i Fabaceae. Stwierdzono, że syntaza homospermidyny (HSS) jest kluczowym enzymem katalizującym powstawanie hompspermidyny z poliamin. Badania kinetyki enzymu oraz sekwencji genów ujawniły jego polifiletyczne pochodzenie: powstał on w wyniku duplikacji genu syntazy deoksyhypuzyny (DHS). Zdolność do produkcji alkaloidów pirolizydynowych pojawiła się w toku ewolucji przynajmniej cztery razy niezależnie w różnych liniach rodowych. Biosynteza PA jest ściśle związana z fazą wzrostu i produkcją biomasy. Przypuszcza się, że biosynteza tych związków jest odmiennie regulowana (indywidualnie) w różnych grupach roślin produkujących alkaloidy. PA pochodzące od necyny z podwójnym wiązaniem w położeniu 1,2 ich estrów działają toksycznie: hepatotoksycznie, rakotwórczo, cytotoksycznie, teratogennie i mutagennie. Za główny mechanizm prowadzący toksyczności uważa się formowanie piroli PA (estry dihydropirilizydyny), które powstają w procesie detoksykacji w wątrobie. Bardzo reaktywne pirole wiążą się z dużymi cząsteczkami protein i kwasów nukleinowych, a także kompleksów DNA-białko, powodując działanie hepatoksyczne i rakotwórcze. Problem toksyczności alkaloidów pirolizydynowych skutkuje ograniczeniami i restrykcjami w produkcji i sprzedaży produktów zielarskich zawierających rośliny produkujące PA. Praca przedstawia obecny stan badań dotyczących alkaloidów pirolizydynowych i obejmuje takie zagadnienia jak: budowa chemiczna, biosynteza, ewolucja z uwzględnieniem powiązanych genów oraz czynniki wpływające na biosyntezę i gromadzenie, a także toksyczność PA.

Słowa kluczowe

EN

pyrrolizidine alkaloid; deoxyhypusine synthase; homospermidine synthase; secondary metabolite; biosynthesis; metabolic pathway; toxicity; medicinal use; Asteraceae; Boraginaceae; Fabaceae

• Wydawca: -
• Czasopismo: Herba Polonica
• Rocznik: 2009
• Tom: 55
• Numer: 4
• Opis fizyczny: p.127-147,fig.,ref.

Twórcy

autor

Dreger M

• Institute of Natural Fibres and Medicinal Plants, Libelta 27, 61-707 Poznan, Poland

autor

Stanislawska M.

autor

Krajewska-Patan A.

autor

Mielcarek S.

autor

Mikolajczak P.L.

autor

Buchwald W.

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