Sparteine

File:BiosynthesisofSparteine.png

Sparteine is a lupin alkaloid containing a tetracyclic bis-quinolizidine ring system derived from three C₅ chains of lysine, or more specifically, {{small|L}}-lysine.{{cite book |vauthors=Dewick PM |date=2009 |title=Medicinal Natural Products: A Biosynthetic Approach |edition=3rd |publisher=Wiley |pages=328–329 |doi=10.1002/9780470742761 |isbn=978-0-470-74276-1}} The first intermediate in the biosynthesis is cadaverine, the decarboxylation product of lysine catalyzed by the enzyme lysine decarboxylase (LDC).{{cite journal |vauthors=Golebiewski WM, Spenser ID |date=1988 |title=Biosynthesis of the lupine alkaloids. II. Sparteine and lupanine |journal=Canadian Journal of Chemistry |volume=66 |issue=7 |pages=1734–1748 |doi=10.1139/v88-280 |doi-access=free}} Three units of cadaverine are used to form the quinolizidine skeleton. The mechanism of formation has been studied enzymatically, as well as with tracer experiments, but the exact route of synthesis still remains unclear.

Tracer studies using ¹³C-¹⁵N-doubly labeled cadaverine have shown three units of cadaverine are incorporated into sparteine and two of the C-N bonds from two of the cadaverine units remain intact.{{cite journal |vauthors=Rana J, Robins DJ |date=1983 |title=Quinolizidine alkaloid biosynthesis: Incorporation of [1-amino-¹⁵N,1-¹³C]cadaverine into sparteine |journal=Journal of the Chemical Society, Chemical Communications |volume=1983 |issue=22 |pages=1335–1336 |doi=10.1039/C39830001335}} The observations have also been confirmed using ²H NMR labeling experiments.{{cite journal |vauthors=Fraser AM, Robins DJ |date=1984 |title=Incorporation of chiral [1-²H]cadaverines into the quinolizidine alkaloids sparteine, lupanine, and angustifoline |journal=Journal of the Chemical Society, Chemical Communications |volume=1984 |issue=22 |pages=1477–1479 |doi=10.1039/C39840001477}}

Enzymatic evidence then showed that the three molecules of cadaverine are transformed to the quinolizidine ring via enzyme bound intermediates, without the generation of any free intermediates. Originally, it was thought that conversion of cadaverine to the corresponding aldehyde, 5-aminopentanal, was catalyzed by the enzyme diamine oxidase.{{cite book |vauthors=Aniszewski T |date=2007 |title=Alkaloids – Secrets of Life: Alkaloid Chemistry, Biological Significance, Applications and Ecological Role |url=https://books.google.com/books?id=a1Z6oJL-dgMC&pg=PA98 |publisher=Elsevier |pages=98–101 |doi=10.1016/B978-0-444-52736-3.X5000-4 |isbn=978-0-444-52736-3}} The aldehyde then spontaneously converts to the corresponding Schiff base, Δ¹-piperideine. Coupling of two molecules occurs between the two tautomers of Δ¹-piperideine in an aldol-type reaction. The imine is then hydrolyzed to the corresponding aldehyde/amine. The primary amine is then oxidized to an aldehyde followed by formation of the imine to yield the quinolizidine ring.

More recent enzymatic evidence has indicated the presence of 17-oxosparteine synthase (OS), a transaminase enzyme.{{cite book |vauthors=Wink M, Hartmann T |veditors=Zalewski RI, Skolik JJ |date=1985 |chapter=Enzymology of quinolizidine alkaloid biosynthesis |chapter-url=https://archive.org/details/naturalproductsc0000inte/page/511/mode/1up |chapter-url-access=registration |title=Natural Products Chemistry 1984: A Collection of Invited Section and Colloquium Lectures Presented at the 14th IUPAC International Symposium on the Chemistry of Natural Products, Poznań, Poland, 9–14 July 1984 |url=https://archive.org/details/naturalproductsc0000inte |url-access=registration |series=Studies in Organic Chemistry |volume=20 |publisher=Elsevier |pages=511–520 |isbn=978-0-444-42457-0}}{{cite journal |vauthors=Wink M |date=1987 |title=Quinolizidine alkaloids: Biochemistry, metabolism, and function in plants and cell suspension cultures |journal=Planta Medica |volume=53 |issue=6 |pages=509–514 |doi=10.1055/s-2006-962797 |doi-access=free |pmid=17269092}}{{cite journal |vauthors=Wink M, Hartmann T |date=1979 |title=Cadaverine–pyruvate transamination: The principal step of enzymatic quinolizidine alkaloid biosynthesis in Lupinus polyphyllus cell suspension cultures |journal=FEBS Letters |volume=101 |issue=2 |pages=343–346 |doi=10.1016/0014-5793(79)81040-6 |doi-access=free |pmid=446758|bibcode=1979FEBSL.101..343W }}{{cite journal |vauthors=Perrey R, Wink M |date=1988 |title=On the role of Δ1-piperideine and tripiperideine in the biosynthesis of quinolizidine alkaloids |journal=Zeitschrift für Naturforschung |volume=43c |issue=5–6 |pages=363–369 |doi=10.1515/znc-1988-5-607 |doi-access=free}}{{cite book |vauthors=Saito K, Murakoshi I |veditors=Atta-ur-Rahman |date=1995 |chapter=Chemistry, biochemistry and chemotaxonomy of lupine alkaloids in the Leguminosae |title=Structure and Chemistry (Part C) |series=Studies in Natural Products Chemistry |volume=15 |publisher=Elsevier |page=537 |doi=10.1016/S1572-5995(06)80142-0 |isbn=978-0-444-82083-9}}{{cite book |vauthors=Roberts MF |veditors=Roberts MF, Wink M |date=1998 |chapter=Enzymology of alkaloid biosynthesis |chapter-url=https://archive.org/details/alkaloidsbiochem0000unse |url-access=registration |title=Alkaloids: Biochemistry, Ecology, and Medicinal Applications |url=https://archive.org/details/alkaloidsbiochem0000unse/page/112/mode/1up |chapter-url-access=registration |publisher=Plenum Press |pages=112–114 |doi=10.1007/978-1-4757-2905-4_5 |isbn=978-1-4757-2905-4}} The deaminated cadaverine is not released from the enzyme, thus is can be assumed that the enzyme catalyzes the formation of the quinolizidine skeleton in a channeled fashion . 7-oxosparteine requires four units of pyruvate as the NH₂ acceptors and produces four molecules of alanine. Both lysine decarboxylase and the quinolizidine skeleton-forming enzyme are localized in chloroplasts.{{cite journal |vauthors=Wink M, Hartmann T |date=1980 |title=Enzymatic synthesis of quinolizidine alkaloids in lupin chloroplasts |journal=Zeitschrift für Naturforschung |volume=35c |issue=1–2 |pages=93–97 |doi=10.1515/znc-1980-1-218 |doi-access=free}}

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• Lupinus
• Lupin poisoning

{{NIE Poster|Sparteine}}

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{{Antiarrhythmic agents}}

Category:Antiarrhythmic agents

Category:Quinolizidine alkaloids

Category:Sodium channel blockers