Alkaloid

 질소 함유 식물성분으로 Biogenic Amine을 제

외한 것임.
 아미노산의 최종 대사 산물로 Polyketide,
Peptide, Terpenoid 등과 함께 생합성 됨.
 주로 염기성이나 중성 또는 약산성의 Alkaloid
도 있음.
 대부분 강한 생리 활성이 있으며, 식물의 방어
물질 또는 최종 대사산물로 추정.
Biosynthesis
of
Amino Acid

식물은 20개의
필수 아미노산을
스스로 생합성함
Amino Acid Biosynthesis
 Nitrogen Fixation is the process by which
atmospheric nitrogen (N2) is captured by certain
organisms and converted into NH3, a form of
nitrogen that can be used by all organisms.
 Just as carbon fixation can be performed by only
certain organisms (eg. photosynthetic), nitrogen
fixation is performed only by a small number of
bacterial species, including symbiotic bacteria
(Rhizobium) in the roots of leguminous plants.
 As you might predict, the reduction of N2 to NH3
is a highly endergonic process (see Figure 13.1):
 Nitrogen fixation is catalyzed by a nitrogenase
complex
 Electrons (& energy from reduction potential)
are derived from 4 NADH
 At least 16 ATP must be hydrolyzed
 The ammonia (NH3) produced is either utilized
by the nitrogen-fixing bacteria, or secreted into
the environment
 In the case of symbiotic nitrogen-fixing
bacteria, the NH3 is transported into adjacent
host cells (where it is used in glutamine
synthesis)
 Note that a byproduct of nitrogen fixation is
hydrogen gas (H2)
Amino Acid Biosynthesis
Amino Acid Biosynthesis:
 Most prokaryotes, many simple eukaryotes, and
plants can synthesize all 20 amino acids used in
protein synthesis from simple organic precursors
and metabolic intermediates
 Mammals and other animals can only synthesize
a subset of these amino acids; known as the 12
"nonessential" amino acids (see Table 14.1)
 The remaining amino acids (8 "essential"
amino acids) must be obtained from the diet
 this explains one of the primary reasons for
the requirement of protein in the diet
 "Complete" proteins contain adequate
amounts of all the essential amino acids
 generally derived from animals (meat, milk,

eggs)
 "Incomplete" proteins are deficient in one or
more of the essential amino acids
 generally derived from plants

 examples: beans (low in methionine),

cereal grains (low in lysine), corn protein

(low in lysine & tryptophan), wheat protein
(low in lysine)
Glutamate Family
 Glutamate (glutamic acid) is derived from a-ketoglutarate , an
intermediate in the Krebs Cycle, through direct incorporation of
ammonium (NH4+):

 Glutamine is derived from glutamate through direct incorporation

of ammonium (NH4+):
 Proline and arginine are derived from glutamate through two very
different biosynthetic pathways.
 Proline is synthesized through reduction of the carboxylic
acid in the side chain of glutamate

 Many amino acid biosynthetic pathways involve transamination

reactions:
 The a-amino group from one amino acid is transferred to an
a-keto acid to produce a new amino acid
 Glutamate is a primary amino group donor in these reactions
(see serine biosynthesis below):
Serine Family
 Serine is derived from 3-phosphoglycerate (glycerate-3-
phosphate), an intermediate in the energy-yielding phase of
glycolysis, through a series of reactions that include
transamination (with glutamate as the amino group donor):
 Glycine is derived from serine by removal of the hydroxymethyl
group from the side chain:

 Asparagine is derived from glutamine through a transamination

reaction (the amino group is derived from the glutamine side
chain, rather than the a-amino group):
Pyruvate Family
 Alanine is derived from pyruvate , the end product of glycolysis,
through a transamination reaction (with glutamate as the amino
group donor):

Histidine Biosynthesis
 Histidine is synthesized through a complicated biosynthetic
pathway that involves the production of phosphorylated
nucleoside intermediates
Alkaloids: Introduction
 small organic molecules (secondary metabolites) of
plants which contain nitrogen (ussually in a ring)
 alkaloids, protoalkaloids, pseudoalkaloids
 structurally diverse: 12,000+ structures
20% of all plant species
 concentrated in specific plant taxa (families, genera,
species)
 biosynthetically diverse (families/types)
 strong biological effects (-> 3 ecological examples)
Historical and human importance:

 pharmaceutically significant (often neurological)

 effect of N
 biological effects & uses:
 analgesic - pain killers (morphine)
 paralysis, anesthesia (tubocurarine, coniine)

 stimulants (caffeine, nicotine)

 antitussive (codeine)

 emetic (emetine)

 anti-cancer drugs (taxol, vinblastine)

 toxins and antibiotics (quinine, sanguinarine)

Alkaloid Families and Biosynthesis

 families classified by ring structure

 derived from amino acids [with a few exceptions]
Examples:
 tyrosine -> morphine (opium alkaloids)

 tryptophan -> quinine (quinoline)

 vinblastine (indole)

 glutamate (via ornithine) -> cocaine (tropane)

• - >nicotine (tobacco alk)

• - > senecionine (pyrrollizidine)
 aspartate -> nicotine

 xanthine -> caffeine, theobromine (purine)

General Features of
Alkaloid Biosynthesis
 can have complex structures, many biosynthetic
steps & compartments (eg) vinblastine
 often found in mixtures of related compounds

 pathway begins with decarboxylation (eg) tyr ->

tyramine
 may include other components - (eg) vinblastine,
(dimeric indole terpenoid) solanidine (tripterpene
alkaloids of potato)
 organ specific synthesis and storage (bark, roots,
flowers)
 sequestered within cells and special structures
(vacuole, latex vesicles, idioblasts, epidermis)
Biosynthesis
of Alkaloid
Steroid Alkaloid

 the Solanum type - one example is solanidine. This steroid

alkaloid is the nucleus (i.e. aglycone) for two important
glycoalkaloids, solanine and chaconine, found in potatoes.
Other plants in the Solanum family including various
nightshades, Jerusalem cherries, and tomatoes also contain
solanum-type glycoalkaloids. Glycoalkaloids are glycosides of
alkaloids.
 the Veratrum type. There are more than 50 Veratrum alkaloids
including veratramine, cyclopamine, cycloposine, jervine, and
muldamine occurring in plants of the Veratrum spp. The
Zigadenus spp., death camas, also produces several veratrum-
type of steroid alkaloids including zygacine
Summery of Alkaloids

 very toxic plant chemicals in common plant species

 toxic chemicals in food plants
 effective against generalist insects, but specialists have
counteradapted
 many alkaloids have documented multiple effects on different
targets
 neurotransmitter receptors (nicotine, cocaine, morphine)

 neurotransmitter transport/degradation (cocaine)

 interfere with cytoskeleton (tubulin - taxol)

 ion channels (caffeine)

 enzyme inhibitors (caffeine, theobromine)