Mevalonate PathwayTerpenes & Steroids
Reyes, Patrick A.BS Chemistry for Teachers
Philippine Normal UniversityTaft Avenue, Manila
• Also known as HMG –CoA (3-hydroxy-3-methylglutaryl CoenzymeA) or Mevalonate – dependent route
• Precursor of terpenes and steroids production
MevalonatePathway
MevalonatePathway
1st step
Formation of HMG-CoA
MevalonatePathway
Acetyl CoA Acetoacetyl CoA HMG CoA
HMG CoA Synthase
Formaton of MevalonateMevalonatePathway
HMG CoA Mevalonate
HMG CoA Reductase
Formation of 5-phosphomavalonateMevalonatePathway
5-phosphomevalonate
Mevalonate kinase
Mevalonate
Formation of 5-pyrophospomevalonateMevalonatePathway
5-phosphomevalonate 5-pyrophosphomevalonate
Phosphomevalonate Kinase
Formation of IPPMevalonatePathway
5-pyrophosphomevalonate
3-isopentyl pyrophosphate
Mevalonate-5-pyrophosphate decarboxylase
Formation of DMAPP
MevalonatePathway
3-isopentyl pyrophosphate Dimethylallyl pyrophosphate
Isopentyl pyrophosphate isomerase
These five carbons are responsible for formation af all terpenes
TERPENES
MevalonatePathway
Terpenes• Terpenes are derived biosynthetically from
units of isoprene
MevalonatePathway
C CC C
C
isoprene isoprene unit
head
tail
natural rubber
D
C C
C
C C
.
JOINING ISOPRENE UNITSHead-to-Tail
Tail-to-Tail
The terms head-to-tail andtail-to-tail are often used todescribe how the isopreneunits are joined.
an extrabond
larger terpenoidunits dimerizetail-to-tail
individualisoprene units join head-to-tail
….. explained later
MevalonatePathway
CLASSIFICATION OF TERPENESTYPE OF NUMBER OF ISOPRENE TERPENE CARBON ATOMS UNITS
hemiterpene
terpenesesquiterpenediterpene
triterpene
tetraterpene
C5
C10
C15
C20
C30
C40
one
two three four
six
eight
hemi = half di = twosesqui = one and a half tri = three
tetra = four
NOTE:
sesterterpene C25 five
MevalonatePathway
SOME TERPENES (C10)CH2OH
OH
a-pinenecamphor
geraniol mentholrose and other flowers peppermint
camphor tree turpentine
O
MevalonatePathway
SESQUITERPENES
CH3
CH3
CH CH3
CH3guaiazulenegeranium oil
CH3
CH3CH3
caryophylleneoil of cloves
MevalonatePathway
MevalonatePathway
HOW TERPENES ARE FORMED?
CH2H
CH2
CH3
OPP
CH3H
CH2
CH3
OPP
IPP DMAPP
CH3
CH2
H
OPPCH2OPP
CH2 OPP
H
OPP
C5 C10
CH2 OPP
CH2 OPP
C15C20
C5isopentenyl-PP3,3-dimethylallyl-PP
C10geranyl-PP
C15
farnesyl-PP
C20
geranyl-geranyl-PP
CONCATENATION OF C5 (ISOPRENE) UNITS
:B
again
TAIL
HEAD
EACH NEW UNIT IS JOINED HEAD-TO-TAIL
DIMERIZATION OF C15 AND C20 UNITS
CH2
CH3
R
OPPCCH3
O
R
PO OO
CH2
CH3
R
PO OO
CH
CH3
O
R
H
CH3
R
PO OO
CH3
O
RCH2
CHCH3
RH
CH3
R
H:-
NADH NAD+
Enz-B:
P OOO
OCH2
CH3 R
rearrange
dimerize
TAIL
TAIL
JOINED SYMMETRICALLY TAIL-TO-TAILUNITS ARE JOINED TAIL-TO-TAIL