Metabolic pathways involve linked series of chemical reactions that occur within cells. Catabolic pathways generate energy by breaking down molecules, while anabolic pathways require energy to build molecules. Key metabolic pathways include glycolysis, the Krebs cycle, and the shikimic acid, mevalonic acid, and acetate-malonate pathways. These pathways provide precursors and building blocks that are tapped off for the biosynthesis of secondary metabolites.

1. BASIC METABOLIC
PATHWAYS

2. • Metabolic pathway is a linked series of chemical reactions occurring within a
cell.
• The reactants, products, and intermediates of an enzymatic reaction are
known as metabolites.
• Pathways are required for the maintenance of homeostasis within an
organism and the flux of metabolites through a pathway is regulated depending
on the needs of the cell and the availability of the substrate.
• Metabolic pathways can be classified as Energy utilizing (anabolic) Energy
generating (catabolic)
• Catabolic pathway: A catabolic pathway is an exergonic system that produces
chemical energy in the form of ATP, GTP, NADH, NADPH, FADH2, etc. from
energy containing sources such as carbohydrates, fats, and proteins. The end
products are often carbon dioxide, water, and ammonia.
• Anabolic pathways: These require an energy input to construct
macromolecules such as polypeptides, nucleic acids, proteins, polysaccharides,
and lipids.

3. • The building blocks for secondary metabolites are derived from primary metabolism.
• Metabolites from photosynthesis, glycolysis, and the Krebs cycle are tapped off from
energy-generating processes to provide biosynthetic intermediates.
• The most important building blocks used in the biosynthesis of secondary metabolites are
derived from the intermediates acetyl coenzyme A (acetyl-CoA), shikimic acid, mevalonic
acid, and 1-deoxyxylulose 5-phosphate.
• These are utilized respectively in the acetate, shikimate, mevalonate, and deoxyxylulose
phosphate pathways.
• In addition to acetyl-CoA, shikimic acid, mevalonic acid, and deoxyxylulose phosphate,
other building blocks based on amino acids are frequently employed in natural product
synthesis.
• Living plants are solar-powered biochemical and biosynthetic laboratory which
manufactures both primary and secondary metabolites from air, water, minerals and
sunlight.
• The primary metabolites like sugars, amino acids & fatty acids that are needed for general
growth & physiological development of plant which distributed in nature & also utilized as
food by man. The secondary metabolites such as alkaloids, glycosides, Flavonoids, volatile
oils etc. are biosynthetically derived from primary metabolites.

5. SHIKIMIC ACID
PATHWAY

6. Shikimic acid
• Commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and
• a cyclohexanecarboxylic acid.
• It is an important biochemical metabolite in plants and microorganisms.
• Its name comes from the Japanese flower shikimi the Japanese star anise,
Illicium anisatum), from which it was first isolated in 1885 by Johan Fredrik
Eykman.
• The elucidation of its structure was made nearly 50 years later.
• Shikimic acid is also the glycoside part of some hydrolysable tannins.
• The shikimate pathway is a seven step metabolic route used by bacteria, fungi,
algae, parasites, and plants for the biosynthesis of aromatic amino acids
(phenylalanine, tyrosine, and tryptophan).
• This pathway is not found in animals; therefore, phenylalanine and tryptophan
represent essential amino acids that must be obtained from the animal's diet
• Animals can synthesize tyrosine from phenylalanine, and
therefore is not an essential amino acid except for individuals
unable to hydroxylate phenylalanine to tyrosine).

8. Shikimic Acid Pathway

9.  Shikimic acid pathway starts with the precursors, Erythrose 4-phosphate and
Phosphoenolpyruvate coupling to form 3-deoxy-D-arabino-heptulosonic acid-7-
phosphate (DAHP).
 Reaction catalysed by phospho-2-oxo-3-deoxyheptonate aldolase. The enzyme, 3 -
dehydroquinate synthase, catalysing the cyclization of DAHP to 3-dehydroquinic acid,
(DHQ). It requires cobalt (II) and nicotinamide adenine dinucleotide (NAD) as
cofactors.

11.  Prephenic acid is then
synthesized by a Claisen
rearrangement of chorismate by
Chorismate mutase. Prephenate
is oxidatively decarboxylated
with retention of the hydroxyl group
by Prephenate dehydrogenase to
give p- hydroxyphenylpyruvate,
which is transaminated using
glutamate as the nitrogen source to
give tyrosine and α-ketoglutarate.

12. The formation of chorismic acid is an important branch point in the shikimic acid pathway as
this compound can undergo three different types of conversion.
In the presence of glutamine, chorismic acid is converted to anthranilic acid, whereas
chorismate mutase catalyses the formation of prephenic acid.
Chorismic acid is also converted into p-aminobenzoic acid. Then after anthranilic acid is
converted first to phosphoribosyl anthranilic acid and then to
carboxyphenylaminodeoxyribulose-5-phosphate, these reactions being catalysed by
anthranilate phosphoribosyl transferase and phosphoribosyl anthranilate isomerase,
respectively.
Ring closure to form indolyl-3-glycerol phosphate is catalysed by indolyl-glycerol phosphate
synthase.
The enzyme catalysing the final reaction, that is, tryptophan synthase consists of two
components; component A catalyses the dissociation of indolylglycerol phosphate to indole
and glyceraldehydes-3-phosphate, whereas component B catalyses the direct condensation of
indole with serine to form tryptophan.

13. Tyrosine and phenylalanine are both biosynthesized from
prephanic acid, but by independent pathways, which act as a
precursor for the biosynthesis of phenylpropanoids.
The phenylpropanoids are then used to produce flavonoids,
coumarins, lignin and tannins. In the formation of tyrosine,
prephanic acid is first aromatized to 4-hydroxyphenylpyruvic
acid, a reaction catalysed by prephenate dehydrogenase.
Transamination, catalysed by tyrosine aminotransferase, then
gives tyrosine.
The biosynthesis of phenylalanine involves first the
aromatization of prephanic acid to phenyl pyruvic acid, a
reaction catalysed by prephenate dehydratase, and then
transamination catalysed by phenylalanine aminotransferase,
which gives phenylalanine.

15. Uses / Role of Shikimic Acid Pathway:
• Starting Point in the Biosynthesis of Some Phenolics
Phenyl alanine and tyrosine are the precursors used in the biosynthesis of
phenylpropanoids. The phenylpropanoids are then used to produce the
flavonoids, coumarins, tannins and lignin.
• Gallic acid biosynthesis:
Gallic acid is formed from 3-dehydroshikimate by the action of the enzyme
shikimate dehydrogenase to produce 3,5-didehydroshikimate.Thelatter
compound spontaneously rearranges to gallic acid.
• Shikimic acid is a precursor for:
 indole, indole derivatives and aromatic amino acid tryptophan and tryptophan
derivatives such as the psychedelic compound dimethyltryptamine.
 many alkaloids and other aromatic metabolites.
• In the pharmaceutical industry, shikimic acid from the Chinese star anise (Illicium
verum) is used as a base material for production of oseltamivir (Tamiflu).
 Shikimate can be used to synthesize (6S)-6-Fluoroshikimic acid, an antibiotic
which inhibits the aromatic biosynthetic pathway.

16. MEVALONIC ACID PATHWAY

17. Mevalonic acid is a precursor in the biosynthetic pathway known as the
mevalonate pathway that produces terpenes and steroids. Mevalonic
acid is the primary precursor of isopentenyl pyrophosphate (IPP), that is
in turn the basis for all terpenoids.
The mevalonate pathway, also known as the isoprenoid
pathway or HMG-CoA reductase pathway is an essential metabolic
pathway present in eukaryotes, archaea, and some bacteria.
The pathway produces two five-carbon building blocks
called isopentenyl pyrophosphate (IPP) and dimethylallyl
pyrophosphate (DMAPP), which are used to make isoprenoids, a diverse
class of over 30,000 biomolecules such as cholesterol, vitamin
K, coenzyme Q10, and all steroid hormones.
The mevalonate pathway begins with acetyl-CoA and ends with the
production of IPP and DMAPP. It is best known as the target of statins, a
class of cholesterol lowering drugs. Statins inhibit HMG-CoA
reductase within the mevalonate pathway.

18. The pathway begins with acetyl CoA molecule produced from pyruvic acid, which is
the end product of glycolysis.
First 2 molecules of acetyl CoA forms acetoacetyl CoA through Claisen condensation.
3 rd molecule of acetyl CoA forms β-hydroxy β-methylglutaryl-CoA by aldol addition.
Next on reduction gives rise to mevalonic acid, which is the main precursor for
biosynthesis of terpenoids.
Mevalonic acid on ATP mediated phosphorylation gives mevalonic acid diphosphate
which on decarboxylation gives the 1st isoprene unit, isopentyl pyrophosphate (IPP).
By the isomerase enzyme, the IPP gives 2nd isoprene unit Dimethyl allyl
pyrophosphate (DMAPP)
Electrophilic addition of IPP with DMAPP via enzyme prenyl transferase yield C10
unit, geranyl pyrophosphate (GPP), which is the precursor for synthesis of
monoterpenes.
Steps Involved

19. Combinations of another IPP unit with GPP give rise to form farnesyl pyrophosphate
(FPP), C15 unit which acts as a precursor for the synthesis of sesquiterpene.
Further addition of IPP unit gives C20 geranyl geraniol pyrophosphate (GGPP) to
produce a range of Diterpenes
On further addition of IPP unit gives C25 geranyl farnesyl pyrophosphate called
Sesterterpenes.
The tail to tail addition of two FPP units yields C30 unit, triterpene. Similarly 2 units
of GGPP yield C40 unit, tetraterpene.
The acetate mevalonate pathway thus works through IPP and DMAPP via squalene
to produce two different skeleton containing compounds, that is, steroids and
triterpenoids. It also produces vast range of monoterpenoids, sesquiterpenoids,
diterpenoids, carotenoids, polyprenols, and also the compounds like glycosides and
alkaloids in association with other pathways

21. 7
Isopentyl Diphosphate: The Biological Isoprene Unit.
Mevalonic acid is the biosynthetic precursor to the actual
C5 “isoprene units,” which are isopentyl diphosphate (IPP, tail) and dimethylallyl
diphosphate (DMAPP, head)
H2C SC oA
O
C
O
O
SCoA
HO2C
H 3 C O H O
3-H ydroxy-3 -m ethylglutaric acid
(H M G-C oA)
HM G-Co A
reductase
2 NADPH OH
HO2C
H 3 C OH
M evalonic acid
O
B:
acetyl CoA
B H
aldol
condensation
HM G-Co A
synthase
H 2 C C SC o A
H
SC oA
acetoacetyl CoA
O
H 2 C C S C o A
H
B:
O
C
H2C SCoA
acetyl CoA
O
O
Claisen
condensation
SCoA
ace toacetyl CoA
O
H3C C S-C ys-E nzym e
acetyl CoA
acetoacetyl-C oA
acetyltransferase
O
H 3 C C S C o A
Enzym e-C ys-S H

22. Conversion of mevalonic acid to IPP and DMAPP
OH
HO2C
H 3 C OH
M evalonic acid
ATP AMP
O -
O O
O P O P O -
O-
O
O H 3 C O H
H
rearrangm ent
O
-
O -
O. O
P. O P
O O
-
H
dim ethylallyl-PP
(D M APP)
isopentenyl-P P
(IP P)
B:
H+
ATP ADP
2-
3 O PO 3
-
O O
O P O P O O -
O -
O
O H C
H
O -
O O
O P O P O -
O-
H H
B:
CH3
O -
O O
O P O P O -
O-
O
O
H
4
- P O 3 -
Carbon-Carbon Bond Formation in Terpene Biosynthesis.
Conversion of IPP and DMAPP to geraniol-PP and farnesyl-PP
electrophilic
head group
nucleophilic
tail group
electrophilic
head group
nucleophilic
tail group
OPP
OPP
H H
OPP
OPP B:
DMAPP IPP
- O PP
Mg2+
OPP
OPP
H H
B:
OPP
15
farnesyl pyrophosphate (C )
geranyl pyrophosphate (C 10 )
- OPP
Mg2+

23. 9
OPP PPO
squalene
synthase
Conversion of genanyl-PP to monoterpenes
Limonene & -Terpineol
O PP
OPP
geranyl
diphosphate
neryl
diphosphate
OPP
- H +
H
:B
HO
H2O
C=C bond acts
as a nucleophile
-terpineol
limonene

24. ACETATE MALONATE PATHWAY

25. Acetate-MalonatePathway
• Acetate-Malonate pathway includes synthesis of
fatty acids and aromatic compounds with the help
of secondary metabolites.
• Main precursors ofAcetate-Malonate Pathway areAcetyl-
CoAand Malonyl-CoA.
• End product of this pathway can be saturated or
unsaturated fatty acids or polyketides.
• Polyketides are secondary metabolites which further
synthesize aromatic compounds by PolyketidePathway.

27. Precursors
Acetyl-CoA: Starter
Unit
Malonyl-CoA:
ExtenderUnit

28. Acetate-MalonatePathway

32. Amino acid Pathway

33. 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 the diets and 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.