Alkaloid

Biogenic Amine
.
Polyketide,
Peptide, Terpenoid .
Alkaloid
.
,
.

Biosynthesis
of
Amino Acid

20

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 -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 -amino group from one amino acid is transferred to an

-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-3phosphate), 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 -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)