3rd grade, 1st term
Pharmacognasy
(Lec1)
Introduction: General
biosynthesis pathways
Asst. Lect. Shahad Laith
Table of contents
I
Introduction
II
Primary metabolite
III
Biosynthesis of
natural drug
I
Introduction
Pharmacognosy
is the science that deals with the studying of drugs that derived from natural sources such
as plants, animals and microorganism
Pharmacognosy deals with the study of the following:
1. Taxonomy of the natural sources
2. Distribution, description and history of the natural sources
3. The part used of the natural sources for treatment of the disease
4. Collection and storage of the part used
5. Active constituents of the natural sources
6. Biosynthesis, physical and chemical properties of the active
constituents
7. True prescription of the natural drug for treatment of the disease
Natural products
Are defined as organic compounds
in the molecular range 1002000. The term is also applied to
bulk substances from nature,
such as crude plant material,
food stuffs, resin and exudates
from plants or extracts (alcoholic
or water) of plant material.
Medicinal agent sources:
1-Pure natural Compounds e.g.
Clavulanic acid
2- Semi synthetic Compounds e.g.
Acetylsalicylic acid
3-Totally synthetic Compounds
based on natural compounds e.g.
pethidin from morphine
Sources of Natural Drugs
●
Plants are the main source of many organic substances. Some of these natural
substances are economically useful for various scientific and commercial
applications.
These organic substances are synthesized and degraded to form another organic
substances by series of chemical reactions. These chemical reactions as a whole are
termed “metabolism”. These substances are classified into:
1-Primary Metabolites: these are formed by “anabolism” which means the
biosynthesis of organic substances.
2-Secondary metabolites: these are formed by “catabolism” which means the
degradation of the primary metabolites
What are the differences between primary and
secondary metabolites?
Primary metabolites
1.These
substances
are
formed
by
photosynthesis.
2. They have a high molecular weight
3. They are found in high concentration the cells
of the plant..
4.They are source of energy.
5.They have structural and functional role in the
plant.
Examples: Different sugars like glucose,
sucrose, amino acids, fatty acids, DNA,
RNA and proteins.
Secondary metabolites
1-These substances are biosynthetically derived from
primary metabolites by three main pathways;
-Shikimic acid pathway
-Acetate- mevalonate pathway
-Mixed pathway derived from both shikimate &
mevalonate (polyketides pathway)
2-They have small molecular weight
3-They are found in small concentration in the plant
cells
4-They are not a source of energy
5-They have no clear function in the plant but they
have an ecological role such as pollinator
attractants like volatile oils and coloring matter in
II
Primary metabolic pathways
• Metabolites are intermediates in metabolic processes in nature and are
usually small molecules.
• Primary metabolite is directly
involved in normal growth,
development, and reproduction, for example, fermentation products
(ethanol, acetic acid, citric and lactic acid) and cell constituents (lipids,
vitamins, and polysaccharides).
• The building blocks for secondary metabolites are derived from
primary metabolism.
• Metabolites from the fundamental processes of photosynthesis,
glycolysis, and the Krebs cycle are tapped off from energy generating
processes to provide biosynthetic intermediates.
Primary metabolic pathways
Primary metabolic pathways
• By far the most important building blocks employed in the biosynthesis of
secondary metabolites are derived from the intermediates:
III
Biosynthesis of natural drugs
1. Active compounds derived from shikimic acid
pathway (most of aromatic compounds derived from this
pathway).
2. Active compounds derived from acetate-mevalonic
acid pathway (most of non aromatic compounds derived
from this pathway)
3.Mixed pathway derived from both shikimate &
mevalonate( polyketides pathway)
1
Aromatic Biosynthesis: The shikimic acid pathway
• The name of the pathway comes from the name of Japanese flower Shikimi
where shikimic acid was first isolated in 1885. Most medicinally active
secondary metabolites are aromatic compounds.
• This pathway produces the critical aromatic amino acids (phenylalanine,
tyrosine and tryptophan) which are synthetic precursors for many medicinal
compounds. So, it’s the biosynthetic precursor of aromatic amino acids and
tannins, flavonoids, coumarins and others.
• This pathway is present and used by plants, fungi and bacteria however absent
in animals, so animals have no way to synthesize the three aromatic amino
acids therefore they are essential nutrients in animal diet.
• The starting point of this pathway are simple carbohydrates
(primary) derived from glycolysis and pentose phosphate
pathway while it ends with aromatic amino acids to form
aromatic active compounds (secondary).
• Shikimic acid through a series of phosphorylated intermediates
produce chorismic acid which is the most important
intermediate. One branch leads to anthranilic acid then to
Tryptophan. The other branch leads to prephenic acid which
is the last non-aromatic compound in this sequence.
Prephenic acid can be aromatized in 2 ways.
• The first proceeds by dehydration and simultaneous
decarboxylation to yield phenyl pyruvic acid, the direct
precursor of phenylalanine.
• The second occurs by dehydrogenation & decarboxylation to
give p-hydroxy phenyl pyruvic acid, the precursor of
tyrosine. Phenylalanine and tyrosine used in the biosynthesis
of phenylproponoids.
• The shikimic acid pathway is also important in the genesis of
the aromatic building blocks of lignin and in the formation of
some tannins, vanillin and phenylpropane units of the flavones
and coumarins.
Phenylpropenes
Are the simplest of shikimic acid derived biosynthetic subunit.
These secondary metabolites consist purely of an aromatic ring
(C6), with an unsaturated 3-carbon chain (C3), attached to the
ring.
Simplest phenylpropenes are the volatile oils example eugenol,
safrole and anethole which will be discussed in volatile oil later.
Eugenol
Anethole
2
•
•
Acetate –mevalonate pathway (Isoprenoid biosynthesis)
Biosynthesis of non-aromatic compounds: this pathway
biosynthesize aliphatic active compounds (terpenoids and
steroids). It forms the Isoprenoid units which are the building
blocks in terpenoid and steroid biosynthesis.
Acetyl CoA with the presence of another acetyl CoA geranyl
pyrophosphate (gp) combine to form aceto-acetyl-CoA which
with the presence of H2O and another acetyl CoA group forms
the intermediate compound [(3S)-3-Hydroxy-3-methylglutaryl
CoA] (HMG-COA).
• This intermediate is then reduced to give mevalonic acid
(mevalonate) which is then phosphorylated, then
decarboxylated to give the final product (isopentenyl
pyrophosphate) and its isomer dimethyl-allyl-pyrophosphate.
Those compounds are the basic precursors of terpenoids.
Isopentenyl pyrophosphate is inter convertible with dimethylallyl
pyrophosphate.
• Dimethyl allyl pyrophosphate (C5) has a good leaving group
(pyrophosphate) and is very reactive towards nucleophilic
substitution at this position.
•
Isoprenoid synthesis then proceeds by the condensation of
isopentenyl pyrophosphate with the isomeric dimethylallyl
pyrophosphate to yield geranyl pyrophosphate. Further C5
units are added by the addition of more isopentenyl
pyrophosphate. Only the (R)-form of mevalonic acid gives
rise to the terpenoids, the (S)-form appearing to be
metabolically inactive.
3 Polyketide pathway
•Polyketides: are aliphatic compounds (alternating carbonyl and
methylene groups –CO-CH2-) formed from malonyl-CoA and acetylCoA eg; many antibiotics(tetracyclin and erythromycin), fatty acids,
anthrone purgatives glycosides, anthracyclic antitumor agents.
Refrences
⬣ Pharmacognosy and Pharmacobiotechnology
by James E. Robbers (Author), Marilyn K. Speedie (Author), Varro E. Tyler (Author)
Thanks!
Do you have any questions?