2. Metabolic Pathway
• A metabolic pathway is a series of chemical
reactions in a cell that build and breakdown
molecules for cellular processes.
• Vital for the production of both primary and
secondary metabolites.
• Occurs in plants, animals and microorganisms.
• Metabolic processes: All chemical reactions that
occur in the living bodies.
• Metabolic pathways can be classified as
1. Anabolism: Energy utilising
2. Catabolism: Energy generating
6. Glossary of enzyme names
CARBOXYLASE- Catalyses the addition of carbon dioxide to a
molecule, uses biotin as a coenzyme.
TRANSFERASE- Catalyses the transfer of a group from one molecule
to another.
TRANSAMINASE- Transfer amino groups. Uses pyridoxal phosphate
as a coenzyme.
KINASE- Catalyses phosphorylation of some metabolite, usually ATP
as a donor.
PHOSPHATASE- Catalyses hydrolic removal of a phosphate group,
also called dephosphorylation.
PHOSPHORYLASE- Catalyzes the phosphorylic cleavage of a bond.
HYDROLASE- Catalyzes the hydrolic cleavage of some bond.
DEHYDOGENASE- Catalyses oxidation reduction reactions by
transfer of hydrogens.
ACYLTRANSFERASE- transfers acyl groups. Uses coenzyme A as a
enzyme.
9. 1. Shikimic acid Pathway
• Biosynthesis pathway provides precursors for aromatic
molecules in bacteria, fungi, apicomplexan and plants,
but not in animals including human beings.
• Commonly known as its anionic form shikimate, is a
cyclohexene, a cyclitol and a cyclohexanecarboxylic
acid.
• 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.
11. Pathway
• The Shikimic acid pathway is a key intermediate from
carbohydrate for the biosynthesis of C6-C3 units (phenyl
propane derivative).
• The Shikimic acid pathway converts simple carbohydrate
precursors derived from glycolysis and the pentose phosphate
pathway to the aromatic amino acids.
• The shikimate pathway is a 7 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
• Animals can synthesize tyrosine from phenylalanine, and
therefore is not an essential amino acid except for individuals
unable to hydroxylate phenylalanine to tyrosine).
14. Explanation of each step
• Phosphoenol pyruvate and erythrose-
4-phosphate react to form 2-keto-3-
deoxy-7-phosphoglucoheptonic acid,
in a reaction catalyzed by the enzyme
DAHP synthase.
• 2-keto3-deoxy-7-
phosphoglucoheptonic acid is then
transformed to 3-dehydroquinate
(DHQ), in a reaction catalyzed by
DHQ synthase.
• Although this reaction requires
nicotinamide adenine dinucleotide
(NAD) as a cofactor, the enzymic
mechanism regenerates it, resulting in
the net use of no. NAD.
• DHQ is dehydrated to 3-
dehydroshikimic acid by the enzyme 3-
dehydroquinate dehydratase, which is
reduced to shikimic acid by the
enzyme shikimate dehydrogenase,
which uses nicotinamide adenine
dinucleotide phosphate (NADPH) as a
cofactor.
15. • The next enzyme involved is shikimate
kinase, an enzyme that catalyzes the
ATPdependent phosphorylation of
shikimate to form shikimate 3-phosphate.
Shikimate 3-phosphate is then coupled
with phosphoenol pyruvate to give 5-
enolpyruvylshikimate-3-phosphate via the
enzyme 5-enolpyruvylshikimate-3-
phosphate (EPSP) synthase.
• Then 5-enolpyruvylshikimate-3-phosphate
is transformed into chorismate by a
chorismate synthase.
• 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
phydroxyphenylpyruvate, which is
transaminated using glutamate as the
nitrogen source to give tyrosine and α-
ketoglutarate.
17. Role of shikkimic acid pathway
• Starting point in the Biosynthesis of some phenolic
compounds.
• Phenyalanine and tyrosine are the precursors
used in the biosynthesis of phenylpropanoids. The
phenylpropanoids are then used to produce the
flavonoids, coumarins, tannins and lignins.
• Gallic acid synthesis.
• Shikkimic acid is a precursor for indole, indole
derivatives and aromatic amino acid tryptophan and
tryptophan derivatives such as psychedelic
compound trimethyltryptamine.
• Many alkaloid and other aromatic metabolites.
20. 2. Acetate-Mevalonate Pathway
• Also called HMG-CoA (β-Hydroxy β-methylglutaryl-CoA) reductase pathway
and Isoprenoid Pathway
• The pathway produces two five carbon building blocks called Isopentenyl
pyrophosphate(IPP) and Dimethylallyl pyrophosphate(DMAPP)-used to make
Isoprenoids, a diverse class of more than 30,000 biomolecules such as
cholesterol, heme, vitamin A & K, Co-enzymes Q10 and steroids hormones.
• The pathway begins with Acetyl-CoA
• One of the intermediates in this pathway is mevalonic acid. The reactions take place
in the cytosol. The pathway was discovered in the 1950s.
• Occurs in eukaryotes, archaea, higher plants-plastids and some bacteria-
Escherichia coli and pathogens such as Mycobacterium tuberculosis.
• Numerous compounds classed as terpenoids or steroids are biosynthesised by the
acetate-mevalonate pathway.
• The terms terpenoid and isoprenoid are interchangeable, isoprenoid referring to the
five-carbon isoprene unit from which all terpenoids are theoretically derived.
• This isoprene rule, which states that all terpenoids are multiples of the isoprene unit
(C1O, C15, C20, etc.)-Isoprene unit-2 Methyl 1,3-butadiene-, is not strictly
obeyed by natural products, although most compounds classed as terpenoids can be
seen to be derived from such units.
• Terpenes: The Isoprene Rule: Isoprenoids- C10 (terpenes), C15 (sesquiterpenes)
and C20 (diterpenes) plant; essential oils.
21. Structure of Isoprene Unit-2 Methyl 1,3-butadiene, Acetyl
Co-A and two five carbon building blocks called Isopentenyl
pyrophosphate(IPP) and Dimethylallyl
pyrophosphate(DMAPP)
22. Ruzicka isoprene rule: terpenoids are derived from
“isoprene units” (C5)
• The biogenetic isoprene rule or the C5 rule was described in 1953, by
Leopold Ruzicka who explained that terpinoids can be visualized as the
result of linking isoprene units "head to tail" to form chains, which can be
arranged to form rings.
24. Terpenes and terpenoids in short
• Terpenes and terpenoids are the primary constituents of
the essential oils of many types of plants and flowers.
• large and diverse class of organic compounds
• Produced by a variety of plants, particularly conifers, and by
some insects.
• Have a strong odor
• Protect the plants that produce them by deterring herbivores and
by attracting predators and parasites of herbivores.
• Terpenes are hydrocarbons/Terpenoids are modified terpenes
with functional groups and oxidized methyl group moved or
removed at various positions.
• Vitamin A is a terpenoid.
• Essential oils
• Steroids, for example, are derivatives of the triterpene squalene.
25. Types of mevalonate pathway
1. Upper mevalonate pathway:
The mevalonate pathway of eukaryotes, archaea,
and bacteria all begin the same way.
The sole carbon feed stock of the pathway is acetyl-
CoA.
The first step condenses two acetyl-CoA molecules
to yield acetoacetyl-CoA. This is followed by a
second condensation to form HMG-CoA (3-
hydroxy-3- methyl-glutaryl-CoA).
Reduction of HMG-CoA yields (R)-Mevalonate
These first 3 enzymatic steps are called the upper
mevalonate pathway
26. 2. Lower mevalonate pathway:
The lower mevalonate pathway which converts
(R)-mevalonate into IPP and DMAPP has 3
variants.
In eukaryotes, mevalonate is phosphorylated
twice in the 5-OH position,
then decarboxylated to yield IPP.
In some archaea such as Haloferax volcanii,
mevalonate is phosphorylated once in the 5-
OH position, decarboxylated to yield
isopentenyl phosphate (IP), and finally
phosphorylated again to yield IPP (Archaeal
Mevalonate Pathway I).
31. Significances of Mevalonic acid pathway
• Used to make Isoprenoids, a diverse class of more
than 30,000 biomolecules such as cholesterol, heme,
vitamin A & K,Co-enzymes Q10 and steroids
hormones-male and female sex hormones,
Cholesterol, Carotenoids .
• Terpenes and terpenoids are the primary constituents
of the essential oils of many types of plants and flowers.
• Protect the plants that produce them by deterring
herbivores and by attracting predators and parasites of
herbivores.
• Numerous compounds classed as terpenoids or steroids
are biosynthesised by the acetate-mevalonate pathway.
• For the production of essential oils
32.
33. Important links
• https://www.sciencedirect.com/topics/biochemistry-genetics-
and-molecular-biology/mevalonate-pathway
• Azami Y, Hattori A, Nishimura H, Kawaide H, YoshimuraT,
Hemmi H (2014) (R)-mevalonate-3-phosphate is an
intermediate of the mevalonate pathway in Thermoplasma
acidophilum. J Biol Chem 289:15957–15967
• Banerjee A, Sharkey TD. (2014) Methylerythritol 4-phosphate (MEP)
pathway metabolic regulation. Nat Prod Rep 31:10431055
• https://www.slideshare.net/rohillarajat/mevalonate-pathway-
74343294
• Ruzcika, Leopold (1953). "The isoprene rule and the
Biogenesis of terpenic compounds". Cellular and Molecular
Life Sciences. 9 (10): 357-367. doi:10.1007/BF02167631.
34. Amino acid pathway
• Assignment
List out the essential and non-essential amino
acids
Biosynthesis of the following amino acids
Glutamate
Histidine
Serine
Aspartate