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    Ephoderin Biosynthesis

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    Hina Aftab
    - Ephedrine and pseudoephedrine are synthesized by some Ephedra plants and used in traditional Chinese medicine. - The biosynthesis pathway involves the deamination of L-phenylalanine and conversion of cinnamate to benzoate, which react to form the first intermediate 1-phenyl-1,2-propanedione. - This is then transaminated and reduced to form ephedrine or pseudoephedrine through a series of steps, with some enzymes now characterized including phenylalanine ammonia-lyase and an N-methyltransferase.

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    © All Rights Reserved
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    Ephoderin Biosynthesis

    Uploaded by

    Hina Aftab
    41 views4 pages
    - Ephedrine and pseudoephedrine are synthesized by some Ephedra plants and used in traditional Chinese medicine. - The biosynthesis pathway involves the deamination of L-phenylalanine and conversion of cinnamate to benzoate, which react to form the first intermediate 1-phenyl-1,2-propanedione. - This is then transaminated and reduced to form ephedrine or pseudoephedrine through a series of steps, with some enzymes now characterized including phenylalanine ammonia-lyase and an N-methyltransferase.

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    - Ephedrine and pseudoephedrine are synthesized by some Ephedra plants and used in traditional Chinese medicine. - The biosynthesis pathway involves the deamination of L-phenylalanine and conversion of cinnamate to benzoate, which react to form the first intermediate 1-phenyl-1,2-propanedione. - This is then transaminated and reduced to form ephedrine or pseudoephedrine through a series of steps, with some enzymes now characterized including phenylalanine ammonia-lyase and an N-methyltransferase.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    41 views4 pages

    Ephoderin Biosynthesis

    Uploaded by

    Hina Aftab
    - Ephedrine and pseudoephedrine are synthesized by some Ephedra plants and used in traditional Chinese medicine. - The biosynthesis pathway involves the deamination of L-phenylalanine and conversion of cinnamate to benzoate, which react to form the first intermediate 1-phenyl-1,2-propanedione. - This is then transaminated and reduced to form ephedrine or pseudoephedrine through a series of steps, with some enzymes now characterized including phenylalanine ammonia-lyase and an N-methyltransferase.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 4

    L-phenylalanine biosynthesis i

    H:N

    L-phenglalanine

    phenylalanine
    ammonia-lyase (Es): Es-PALI
    ammonium
    4.3.1. 24/4. 3. 1. 25
    glycolysis ll (from fructose 6-phosphate)

    Pyruvate

    cinnamale
    2 H,0
    NAD

    2H
    NADH
    acetate

    =0

    benzoate

    cO,

    I-phengl-1. 2-propanedione
    L-glutamate

    2-oxoglutarate

    NH
    -phengl-i. 2propanedione

    Lglutamale

    2-anglutarate

    eathinene

    NADII S-ealhleoneR
    NADIH -reductase (Ls)

    I,1.1. .I
    NAD"
    NAD"

    (IR. 87-norephedrine
    (S.S-morpdoep
    Sodenosy-L"methionine -
    S-adenosyl-L-methionime-- (IR 2 s r a a F
    8. 28-norpseudoephedrtne
    -methyltsnsfarase' (Es): Es-RNHT Es-oNMT
    2. 1.L H78 -adenosj-l-hanonstRane
    n0s nohocysnine
    21.1 Hr

    HN
    O.

    (1S 28)-pseudoephedrine (IR S-ophedrine

    S-adenosy-L-mcihionine-. S-adenosy-l-methionine- ( p Es
    1S. e (Ls)
    ethransfertse Es-PoNMT
    {La): s-laNNT
    Es-FaNHT
    H76
    adenospl-thoGsteine adenesg--homocysteine 2.1.L.r6

    (HN, 5; (R aS-N-methylephedrine
    N-methy lpseudoephedrine
    pervlassee: PangnthestsSeeandarjy fetabnite uesgathess- Nitrugen-tamtaiing dndary p egms a ya

    Summary
    Ephedrine and pseudoephedrine are plant-specific aromatic
    amines synthesized by some members of the Ephedra genus
    (known as Ma Huang" in Chinese medicine). Ephedrine was first
    isolated from Ephedra distachya in 1886 by Nagayoshi Nagai.
    The compounds are sympathomimetic in humans - they interact

    with the adrenergic receptor system. part of the sympathetie


    nervous system. resulting in an inerease in the release of the
    neurotransmitters dopamine and serotonin. Ephedrine alkaloids
    are used in traditional Chinese medicine for the treatment of
    asthma, and are commonly used as stimulants. appetite
    suppressants, and decongestants. Ephedrine is listed as an
    essential medicine by the World Health Organization for the
    prevention of low blood pressure induced by spinal anesthesia.
    Early work on the ephedrine biosynthesis pathway. using radio
    tracer experiments. showed efficient incorporations of benzoate.
    benzaldehyde and cinnamate into the a-carbon atom of the side
    chain. and coneluded that a Gg-C unit related to benzaldehyde
    or benzoate generates the benzylie fragment of the carbon
    skeleton of he Ephedra alkaloids, ruling out the hypothesis that
    a Cg-C2 unit is derived directly from the aminophenylpropanoid
    system of phenylalanine Lyamasaki73]. A later rodio tracer
    study has eoncluded that pyruvate is the precursor of the
    aliphatie C2 carbon of the side chain [GrueSorense88.
    GrucSorensen89]. Additional work by the authors showed that it
    is benzoate rather than benzaldehyde that comtributes the
    g-C
    unit (GrueSorensen94]. These studies also identified 1-phenyl-
    1.2-propanedione and (S)-cathinone as intermediates. even
    though these compounds have not been previously detected in or

    isolated from any Ephedra species [GrueSorensen94]. The


    existence of both compounds was confirmed later in Ephedra
    sinica using GC-MS analysis [Krizeuskil0].
    Based on the proposed pathway. the first step in the ephedrine
    alkaloid biosynthesis is the deamination of L-phenylalanine by
    EC 4.3.1. 24. phenylalanine ammonia-lyase. The produet.
    cinnamate, is converted into benzoate or benzoyl-CoA by B-
    oxidation. a process that results in braneching off from the
    common phenglpropanoid pathway. These G6-C units react with
    Purvat the dener ef the C2 unit, forming 1-pheny-1. 2-
    unit [GrueSor ensen94J. T hese studies also identific rs

    1.2-propanedione and (S)-cathinone as intermediates.


    even

    detected in
    though these compounds have not been previously
    or

    isolated from any Ephedra species [GrueSorensen94].


    The
    existence of both compounds was confirmed later in Ephedra
    sinica using GC-MS analysis [Krizevskil0].
    Based on the proposed pathway. the first step in the ephedrine
    alkaloid biosynthesis is the deamination of L-phenylalanine by
    EC 4.3.1. 24. phenylalanine ammonia-lyase. The produet.
    cinnamate. is converted into benzoate or benzoyl-CoA by B-
    oxidation. a process that results in branching off from the
    units react with
    common phenylpropanoid pathway. These C6-C1
    C2 unit. forming 1-phenyl-1. 2-
    Pyruvate. the donor of the
    propanedione. which is the first intermediate with the basic C6-
    C3 skeleton of ephedrine alkaloids.
    is
    In the latter part of the pathway 1-phenyl-1. 2-propanedione
    transaminated to (S)-cathinone, which is reduced in a

    stereoselective manner to either (18. 28)- or (1R. 2S)-form


    isomers. W-methylation forms ephedrine and pseudoephedrine.
    respectively [GrueSorensen94].

    At the time the pathway was proposed none of the pathway's


    were characterized. and by 2020 only two of them
    enzymes
    enzyme is EC 4. 3. 1. 24.
    have been isolated. The first
    and the second is EC
    phenylalanine ammonia-lyase [Okada08a].
    [Morris18].
    2.1. 1. M76. phenylalkylamine N-methyltransferase
    sinica. In addition. the activities of
    both studied from Ephedra
    reductases were demonstrated
    two stereo-specific (S)-cathinone
    in cell extracts [Krizevskil0].
    demonstrated the-
    It should be noted that the N-methyltransferase
    that
    with (S)-cathinone. raising the possibility
    highest activity
    occur earlier in the pathuway
    than previously
    N-methylation may
    proposed [Morris18).

    Credits
    Greated 1-Apr-2008 by Zhang P. The Arabidopsis Information
    Resource
    R, SRI International
    Revised 20-May-2020 by Caspi

    References
    GirueSorensen88: Grue-Sorensen Spenser ID (1988).
    G.
    American Chemical
    of ephedrine. Journal of the
    "

    "Rigsunthesis

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