Unit I Metabolic pathways in
higher plants & their determination
Pharmacognosy & Phytochemistry II
B. Pharm. Vth Semester
Biosynthetic Pathways
Metabolic pathways
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Unit 1 Biosynthetic Pathways Pharmacognosy and Phytochemistry II.pdf
1. 1
Pharmacognosy & Phytochemistry II
B. Pharm. Vth Semester
Metabolic pathways in
higher plants & their determination
Unit I
Dr. Amit Gangwal
HoD, Pharmacognosy
I/C: Publicity Wing
Criterion 7 I/C, NAAC
2. Content has been taken from various
sources using Google as search engine.
I don’t have any copyright on these
content/material/images etc.
I am thankful to original creators/right
holders.
2
4. 4
CO Code Course Outcomes
CO504.1 Understand basic metabolic pathways and formation of different
primary & secondary metabolites through different
pathways besides learning how these pathways are traced.
CO504.2 Explain basics related to chemistry, extraction, classification and
various properties pf varied secondary metabolites like alkaloids,
glycosides, phenolics and others.
CO504.3 Explain basics related to chemistry, extraction, classification and
various properties pf varied secondary metabolites like iridoids,
resins, volatile oils etc. and explain and perform isolation,
identification, analysis of various individual secondary metabolites
from plants.
CO504.4 To summarize the modern extraction techniques and examine
applications of latest techniques in the isolation, purification and
identification of crude drugs.
8. What is Biosynthesis?
Process of forming large molecules from smaller
subunits within living organism, done by mainly
enzymes.
Also known as anabolism- simple molecules join to
form macromolecules.
◦ E. g. formation of carbohydrates through photosynthesis
in chloroplast through conversion of light energy into
chemical energy. (synthesis of glucose from
H2O+CO2)
8
14. Metabolism
What is Metabolism?
Metabole: Greek word: Means Change
Metabolic pathway: is a series of steps in biochemical
reactions that help to convert molecules or substrates like
sugar into different usable materials.
All these reactions take place inside cell, enzymes which
are protein molecules, break down or build up molecules.
Enzymes are catalyst to these metabolic reactions.
14
15. 15
Anabolism: synthesis of larger/complex molecules –
requires energy (Glucose → glycogen)
Catabolism: Met. Reac. in cell that degrade substrate into
smaller/simpler products- releases energy (Glucose to
smaller molecules)
Anabolic: Small molecules join into larger ones. Hence
Energy is required
+ Energy
Catabolic: Large Molecules are broken down into the smaller one
and hence energy is released
+ Energy
16. Metabolic pathways
Two types:
Anabolic Pathway: Utilization of energy for
biosynthetic reactions. Utilizes NADH, ATP etc.
Metabolites: intermediates, small mol. products of
metabolism
Primary metabolites- responsible for primary function
for plants’ own growth and development)
Catabolic Pathway: release energy by breaking down
molecules into simpler molecules. Ex. Cellular
respiration: Sugar is taken in by cells and broken down
to release energy.
16
18. Metabolic pathways
Primary metabolites: carbohydrates, lipids, proteins, amino
acids, nucleic acids, cellulose etc.
Not responsible for therapeutic activity
Primary metabolic pathway: pathways followed for
production of primary metabolites
Secondary metabolites: not responsible for growth of
plants
Secondary metabolites: synthesized for adaptation by plants
under stress conditions, toxic subs, for attracting
pollination, for defense etc.
They are therapeutically active.
Ex: Alkaloids, glycosides, tannins, terpenoids etc.
They are the derivatives of primary metabolites.
Synthesis of secondary metabolites: pathway known
Secondary metabolic pathway.
18
19. Metabolic pathways
Primary Metabolic pathways:
1. Glycolysis
2. TCA/ Kreb’s / Citrate pathway/Citric acid cycle
(Tricarboxylic Acid Cycle)
3. Pentose phosphate pathway/ Hexose monophosphate
pathway
Primary metabolic pathway of carbon
1st step is photosynthesis
19
Energy
Water
CO2 Sugar
O2
6CO2 + 6H2O C6H12O6 +6O2
Photosynthesis
24. Metabolic pathways
Sugar or glucose enters Glycolysis cycle &
finally converted to 2 pyruvate.
After glycolysis, pyruvate in presence of O2
(aerobic) is converted to Acetyl CoA.
In TCA cycle - Oxidation of Acetyl CoA takes
place.
24
31. SHIKIMIC ACID PATHWAY
It is an intermediate from carbohydrate for
biosynthesis of phenyl propane derivative
(C6-C3 unit) ex. Tyrosine & phenylalanine
Precursor for synthesis of shikimic acid is
phospho enol pyruvate- (from Glycolysis) &
erythrose-4-phosphate an intermediate of PPP/
HMP
The N required in pathway is obtained from –
other amino acids- Glutamine, glycine, serine.
31
32. Role of Shikimic acid
Precursor for biosynthesis of some phenolic,
phenyl propane derivatives- flavonoid,
coumarin, tannins, lignin
Precursor for indole, indole derivative &
many alkaloids & other aromatic metabolites
Gallic acid biosynthesis from 3 de-
hydroshikimate (intermediate)
32
In the genesis of aromatic building blocks of lignin & in
formation of few tannins, vanillin, phenylpropane units of
flavones & coumarins and also in the formation of
alkaloids.
39. Acetate Pathway
Acetate required for synthesis of various
secondary metabolites in plants.
Starting material is acetate, utilized as acetyl Co-A
(active form of acetate)
Various straight chain or aromatic compounds are
synthesized by acetate pathway.
Acetate Mevalonate Pathway (MAP) contributes to
1/3rd of secondary metabolites.
39
42. 42
Acetate-Mevalonate Pathway
• The role of acetic acid in biogenetic pathways was discovered in
1950 after the discovery of acetyl co -enzyme A ( active acetate ).
• Later, it was discovered that mevalonic acid is associated with
acetate.
• Isopentenyl Pyrophosphate (IPP) and its isomer
Dimethylallyl Pyrophosphate (DMAPP) are produced by
mevalonic acid.
• IPP and DMAPP are the two chief intermediates that set the ‘active
isoprene’ unit as the basic building block of isoprenoid
compounds.
• Both of the units produce geranyl pyrophosphate (C10-
monoterpenes), which further associates with IPP to yield farnesyl
pyrophosphate (C15-sesquiterpenes).
43. Acetate Mevalonate Pathway
Isopentenyl pyrophosphate & its isomer that is dimethyl allyl
pyrophosphate are universal precursors for synthesis of
isoprenoids/terpenoids/volatile oils/cholesterol/saponins/steroids.
Isoprene unit (C5H8) - responsible along with other pathways for
biogenesis of anthraquinone, naphthaquinone, terpenoids etc.
Isoprene units (C5H8)
43
CH3
CH2
C CH CH2
C
CH3
CH2 C
H
CH2
1
2
3
4
5
44. Terpenoids are derived from isoprene units (C5H8)
which are joined in a head-to-tail or head-to-head
fashion.
C5
C10
C15
C20
C25
C30
C40
hemiterpenes
monoterpenes
sesquiterpenes
diterpenes
sesterterpenes
triterpenes
tetraterpenes
CH3
CH2
C CH CH2
51. 51
• Farnesyl pyrophosphate produces geranyl-geranyl
pyrophosphate (C20-diterpenes) by combining with another
unit of IPP.
• Farnesyl pyrophosphate multiplies with its own unit to form
squalene and its successive cyclisation produces
cyclopentanoperhydrophenanthrene skeleton that contains
steroidal compounds (like cholesterol and triterpenoids).
• Thus, two different skeleton containing compounds, i.e.,
steroids and triterpenoids are produced by the acetate
mevalonate pathway working through IPP and DMAPP via
squalene.
• A huge array of monoterpenoids, sesquiterpenoids,
diterpenoids, carotenoids, polyprenols, glycosides, and
alkaloids are also produced in association with other pathway.
54. 54
The sapogenins occurs in glycosidic form of saponins. The neutral
saponins are steroidal derivatives possessing spiroketal side chain
and acid saponins have triterpenoid structure.
The pathway is similar for the biosynthesis of sapogenins. The
triterpenoid hydrocarbon squalene is formed after cyclisation of
triterpenoids in one direction and spiroketal steroids
in other direction.
The squalene, cholesterol and other steroidal compounds including
aglycone are formed in the following manner.
56. 56
Acetate-Malonate Pathway
• With the involvement of Acyl Carrier Protein (ACP), the
acetate pathway works functionally to produce fatty acyl
thioesters of ACP.
• These acyl thioesters build the important intermediates in
fatty acid synthesis.
• In a later stage, even numbers of fatty acids from n -
tetraenoic (butyric) to n -eicosanoic (arachidic acid) are
produced by these C 2 acetyl CoA units.
• Subsequent direct dehydrogenation of saturated fatty acids
produces unsaturated fatty acids.
• Enzymes play a crucial role in directing the position of newly
introduced double bond in the fatty acids.
57. 57
• The acetate pathway is important in the formation of various important
phytoconstituents like fatty acids, polyketides, prostaglandins, aflatoxin,
tetracycline and other various important phytoconstituents.
• For the biosynthesis of fatty acid, the acetyl CoA carboxylated to form
malonyl CoA by the presence of enzyme named acetyl CoA carboxylase.
• The energy requisite for this carboxylation is supplied by ATP and loss of
CO2 occurs.
• After this step reduction, dehydration and again reduction will occur.
• During both reductions process the electron is provided by NADH+ and H+
and the formation of butyryl ALP will occur.
• The coupling between malonyl ALP and butyryl ALP will occur and their
reduction is repeated again for whole chain.
• Malonyl CoA bind again with the fatty acid residue by increase the chain
with two carbon unit.
• The first end product is palmitic acid which has 16 carbon atoms.
• The chain is further elongated by various mechanisms.
59. Amino acid pathway
59
• Plants and bacteria can synthesize all 20 of the amino acids. Whereas
humans cannot synthesize 9 of them.
• These 9 amino acids must come from our diets and therefore they
are called essential amino acids.
• The essential amino acids are Histidine, Isoleucine, Leucine, Lysine,
Methionine, Phenylalanine, Threonine, Tryptophan, and Valine.
• The 11 amino acids are called non-essential amino acids like
Alanine, Arginine, Aspargine, Aspartate, Cysteine, Glutamate, Glutamine,
Glycine, Proline, Serine and Tyrosine.
• The non-essential amino acids are synthesized by simple pathways,
whereas biosynthesis of the essential amino acids are complex. All 3
aromatic amino acids are derived from shikimate pathway.
68. 68
• The carbon skeletons of amino acids are derived from different
intermediates of the central carbon metabolism (boxed in blue).
• According to their respective precursors, the amino acids are grouped
into five families derived from glutamate, serine, pyruvate, aspartate, or
chorismate.
• The nine amino acids that cannot be synthesized in animals are shown
in dark-green boxes, while those that can be synthesized but
additionally need to be taken up with the diet are in brighter boxes.
• Proteinogenic amino acids that can be sufficiently synthesized in
animals are in pale green boxes and non-proteinogenic amino acids
and other important intermediates are boxed in white. DAHP, 3-deoxy-
D-arabinoheptulosonate-7-phosphate.
69. Biosynthesis of Glycosides
69
• The metabolic process of glycoside formation occurs in
two steps:
• In first step various types of aglycone are formed by
biosynthetic reactions whereas in second step coupling
of aglycone with sugar moiety occurs.
• In different types of glycosides interaction of nucleotide
glycoside occurs between UDP-glucose with alcoholic
or phenolic group of secondary compound aglycone
(called O-glycosides), through linkage with carbon (C-
glycosides), nitrogen (N-glycosides) or sulphur (S-
glycosides).
70. 70
The following two steps are involved in this process:
1. In first step, the uridine triphosphate (UTP) transferred an uridylyl
group to sugar-1-phosphate and forms UDP-sugar and inorganic
pyrophosphate. The enzyme which catalyzes this reaction is uridylyl
transferases.
UTP + Sugar-1-PO4 UDP- sugar + PP1
2. In second step, transfer of the sugar moiety from UDP to a suitable
acceptor (aglycone) occurs. This reaction is mediated by enzyme
glycosyl transferases and forms glycoside.
UDP-sugar + Acceptor (aglycone) Acceptor-sugar (glycoside) + UDP
71. 71
• The sugars of glycosides are monosaccharides (like
Rhamnose, Glucose, Frucose or deoxy sugars i.e. digitoxose
or cymarose).
• The aglycone moieties of cardiac glycosides are steroidal in
nature.
• These are derivatives of cyclopentenophenanthrene ring
which contains unsaturated lactone ring attached with C17, a
14-alpha hydroxyl group and a cisjucture of ring C and D.
• The anthraquinone glycosides are biosynthesized from
shikimic acid pathway in Rubiaceae family.
• The alizarin biosynthesis shows ring A is derived from shikimic
acid whereas mevalonic acid is included in ring C.
72. 72
It is very important to understand the biosynthesis of flavonoids due to
their diversity.
These flavonoidal molecules are biosynthesized by their precursor
which is three molecules of acetic acid and phenyl propane moiety.
It mainly involves the interaction of five different pathways which are
named as:
1. The Glycolytic pathway.
2. The Pentose phosphate pathway.
3. The Shikimate pathway that synthesizes phenylalanine
(An amino acid).
4. The phenylpropanoid metabolism that produces activated cinnamic
acid derivatives i.e. 4-coumaroyl-CoA and lignin (also the plant
structural component).
5. The diverse specific flavonoidal pathway.
73. 73
• The flavonoids are biosynthesized via condensation of the shikimic
acid and acylpolymalonate pathways.
• The phenyl propane (cinnamic acid derivative) synthesized from
shikimic acid which acts as a precursor in a polyketide synthesis.
• In this scheme additional three acetate residues are incorporated
into the structure and followed by ring closure.
• The plants biosynthesizes different classes of flavonoids like
flavonols, flavanones, flavones, flavanols or catechins, iso-flavones,
dihydro-flavonols, anthocyanidins, and chalcones through
subsequent hydroxylation and reduction.
75. 75
• In the biosynthesis of Cyanogenetic or Cyanophoric glycosides (e.g.
Prunasin) the amino acid phenylalanine acts as a precursor.
• In this biosynthetic pathway an aldoxime, a nitrile and a cyanohydrin
are involved as intermediate.
• The chiral centre in the mandelonitrile provides the opportunity for 2
β–glucosides to form.
• D-mandelonitrile glucoside is formed in Prunus serotina (wild
cherry) whereas L-mandelonitrile glucoside (isomeric samburgrin) is
found in Sambucus nigra.
• These compounds are not found in same species.
89. 89
What do you understand by study of basic metabolic pathways and formation of
different secondary metabolites?
2. How secondary metabolites are produced from biosynthetic pathways?
3. What is Shikimic acid pathway? Draw its pathway.
4. How glycosides are biosynthesized? Draw its pathway.
5. Draw biosynthetic pathway of Flavonoids.
6. Draw biosynthetic pathway of Isothiocyanate aglycones.
7. Draw biosynthetic pathway of Cyanogenetic glycosides.
8. How secondary metabolites are obtained by Cholesterol metabolism?
9. Draw Acetate pathway.
10. Draw Amino acid pathway.
11. Draw general scheme for amino acid production through pathway.
12. Write a detailed note on utilization of radioactive isotopes in the investigation of
biogenetic studies.
13. What is the role of radioactive tracers? How they are detected?
14. What is autoradiography? Explain precursor product sequence.
15. What is competitive feeding? How precursors are administered in any pathway?
16. What is sequential analysis? Describe briefly.