Download In the previous lecture we mentioned the different pathways of

In the previous lecture we mentioned the different pathways of
biosynthesis of different metabolites.
- There are three major different pathways:
1. The acetate-malonate pathway
2. Mevalonic acid pathway
3. Shikimic acid pathway
-
These pathways are responsible for providing us with many different
metabolites.
Acetate-malonat pathway and Mevalonic acid pathway start their biogenetic
role with acetyl CoA.
Acetyl CoA is a very important building block of two carbons compound, it
is needed in the degradation of carbohydrates and the synthesis of fatty acids,
and appears in Krebs cycle and in the breakdown process of fatty acids.
Acetyl CoA + CO2  Malonyl-CoA “3 carbons”
Shikimic acid is a very important building block of phenolic
substances, because it contains a ring and it’s also important for the formation
of three important amino acids: Phenylalanine, Tyrosine and Tryptophan.
So by using these simple compounds such as shikimic acid or acetyl CoA
we will be able to biosynthesize hundreds or thousands of new compounds
which have physiological (Endogenous) role or therapeutic role.
The scheme you have in sheet 1 (you are not ought to memorize it) shows
how compounds co-exist together with interactions, if there were no primary
metabolites, there would be no secondary metabolites …
Now we will start with acetat-malonate pathway, and specifically with nonaromatic (aliphatic) derivatives.
None-aromatic derivatives in the acetate-malonate pathway polyacetylenic or
polyynes , compounds having several triple bonds.
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The biogenesis of naturally occurring acetylenic substances is very
closely related to the synthesis of unsaturated fatty acids.
In the Plant Kingdome, fatty acids are used to form of triglycerides to produce
oils.
The natural sequence of the fatty acids (even-numbered fatty acids)
starts with Palmatic acid (16 carbons), Stearic acid (18 carbons) and then
Arachidonic acid (20 carbons). Palmatic acid and stearic acid are important in
plants’ oils, these oils are composed of three fatty acids connected to glycerol.
If glycerol is connected to 3 saturated fatty acids, the product is a solid
substance called fat, and its found primarily in animal kingdom (mammals
especially).
When at least two of the hydroxyl groups are connected to unsaturated
fatty acids, the product is termed as Oil, because of its liquid consistency.
Oils are primarily found in plants, but there are some exceptions (like
coconut oil, which is solid).
We went back to mention the previous basic information in biochemistry
about fatty acids because the biogenesis of the natural occurring acetylenic
substances in the plant kingdom or in the microorganisms are closely linked to
the biogenesis of the common fatty acids.
Synthesis of fatty acids using acetyl CoA causes addition of two carbons
to the chain causing chain elongation with two carbons each time.
For the plant kingdom, stearic acid with 18 carbons has a very important role
because its easily converted to unsaturated fatty acid with one double bond at
position 9, Oleic acid  18:1 (9), or to a fatty acid contains 2 double bonds :
Linoleic acid  18:2 (9,12) , or with three double bonds: Linolenic acid  18:3
(9,12,15)
This three unsaturated fatty acids are very important and common in nature.
Mammalian organisms cannot biosynthesize these fatty acids.
The biosynthesis of natural acetylenic substances is linked to the biogenesis of
these unsaturated three fatty acids starting with oleic acid.
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In the majority of the plants, oleic acid will be converted to linoleic acid,
and then linoleic acid will be converted to linolenic acid.
At the stage of linoleic acid, enzymes termed as Dehydrogenases or
Desaturases (names of this enzyme family), an enzyme belongs to this family
called Lenoleic acid Dehydrogenase.
(Each fatty acid has its own Dehydrogenase)
Stearic acid is converted to oleic acid in the presence of the enzyme Oleic
acid Dehydrogenase (Desaturase).
Oleic acid is converted to linoleic acid by the presence of the enzyme Linolenic
acid Dehydrogenase (Desaturase)
So, each enzyme is specific for each fatty acid causing loss of two hydrogen
atoms and the formation of a double bond at specific position on the fatty acid.
In the biogenesis of naturally occurring acetylenic substances, Oleic acid is
converted to linoleic acid, and linoleic acid has two options: 1. Conversion to
Linolenic acid (major).
2. 12,13-Dihydro linoleic acid by the introduction of the first triple bond ,
also called, Crepenynic acid … this occurs in the families: Umbelliferae,
compositae and gramineae … this step happens in some plants by the enzyme
crepenynic acid dehydrogenase.
As soon as the crepenynic acid is formed, the biosynthesis of the
acetylenic substances proceeds.
The object of the biosynthesis of acetylenic substances is to convert the less
unsaturated fatty acid to the more unsaturated fatty acid by increasing the
number of double bonds … Dihydrocrepenynic acid is more unsaturated than
crepenynic acid.
 Till now, we are synthesizing straight chain acetylenic compounds –
The first acetylenic has one carboxyl group as a functional group, and it has 18
carbon atoms, it’s an acid and has only one triple bond.
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The occurring of acetylenic compounds is not only for the plant kingdom, but
also occurs in microorganisms.
Plants and microorganisms together they form more than thousand different
structures based only on crepenynic acid by modifying it  what are the
modifications that can be done on crepenynic acid?
1. Ester: by the addition of alcohol
2. Decarboxylation: to produce simple hydrocarbon chain
3. Oxidation: means the addition of –OH group producing alcohol
4. After the addition of –OH group and obtaining an alcohol, we can add a
carboxylic acid to produce new different esters.
5. Shortening of the chain can be achieved by many different methods: by
beta- oxidation (fat degradation) which shortens the chain with two
carbons, or by alpha-oxidation (happens in plants) shortening with one
carbon.
6. We can convert the end of the aliphatic molecule to an aromatic ring,
such as the formation of phenolic structure
7. Addition of sulfur, oxygen or nitrogen to form a ring contains these three
elements.
 Thiophen ring is very important biologically.
Furan
Pyran
The classification of acetylenic compounds depends on the presence of a
functional group or triple bond, the simplest acetylenic compound will be a
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straight chain hydrocarbon with no functional groups, then by modification
(addition of functional groups) on this simple acetylenic compound it may be
converted to : Fatty acids, alcohols, ketones, esters, aromatics, furans,
thiophens and acetyls with spiroketals.
*something which is very interesting regarding acetylenic compounds
and science cannot explain it till now, their synthesis should continue to reach
a large ,complicated molecule (such as oleic acid, stearic acid or crepenynic
acid), then this molecule becomes shorter with other reactions … Unlike the
synthesis of other substances which starts from small molecules then
synthesis continue to reach larger molecule.
*The physicochemical properties of acetylenic compounds:
1- Lipophilic
2- Unstable
3- Present in very low concentrations.
4-their presence is limited to certain plant families (Gramineae, Umbelliferae,
Compositae)
 Because of their unstability and low concentrations, they needed special
techniques for isolation, so their study started after 1950, which is
considered very lat compared to other organic substances.
*** Echinacin is an immune-stimulating agent which is derived from
Echinacea. This plant is present in North America. Belongs to the family
Compositae (Asteracae: the modern name of this family). Species medicinally
used are: Angustifolia, purpurea(extracts of crude drug is used) and pallida.
Legumes not flowers are used to extract the crude drug. Nowadays, It is
cultured in Jordan. It has a nice appearance.
 Keep in mind that there is never one plant synthesizing only one active
material, usually plants are biosynthesizing several secondary
metabolites belonging to different pathways in the same plant. So you
can have in one plant acetate originating metabolites and mevalonat
originating metabolites (for example). Meaning that there is always a
mixture of metabolites in each plant.
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Echinacin is advised to be taken to improve immunity and to increase one’s
resistant against common cold and microorganisms (works as antibiotic
against staphylococcus).
Some acetylenic compounds are toxic, especially those isolated from
Apiacae, causing very strong convulsions and gastric disturbances.
As we mentioned before, acetylenic compounded can be isolated from
microorganisms. Mycomycine is isolated from microorganisms particularly
from Nocardia acidophilus. It’s a very potent antimicrobial agent, but it is very
unstable (structural reasons) rendering its activity.
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Good Luck
Done by: Arwa Bdair
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