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 Mevalonate

MevalonatePathway

HMG CoA Mevalonate

HMG CoA Reductase

Formation of 5-phosphomavalonate

MevalonatePathway

5-phosphomevalonate

Mevalonate kinase

Mevalonate

Formation of 5-pyrophospomevalonate

MevalonatePathway

5-phosphomevalonate 5-pyrophosphomevalonate

Phosphomevalonate Kinase

Formation of IPP

MevalonatePathway

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 C

C 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 TERPENES

TYPE OF NUMBER OF ISOPRENE TERPENE CARBON ATOMS UNITS

hemiterpene

terpene

sesquiterpene

diterpene

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

CH3

CH3

caryophyllene

oil 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

OPPC

CH3

O

R

PO O

O

CH2

CH3

R

PO O

O

CH

CH3

O

R

H

CH3

R

PO O

O

CH3

O

R

CH2

CH

CH3

RH

CH3

R

H:-

NADH NAD+

Enz-B:

P OO

O

O

CH2

CH3 R

rearrange

dimerize

TAIL

TAIL

JOINED SYMMETRICALLY TAIL-TO-TAILUNITS ARE JOINED TAIL-TO-TAIL