Mevalonate Pathway Terpenes & Steroids Reyes, Patrick A. BS Chemistry for Teachers Philippine Normal University Taft Avenue, Manila

Also known as HMG –CoA (3-hydroxy-3- methylglutaryl CoenzymeA) or Mevalonate – dependent route Precursor of terpenes and steroids production MevalonatePathway

1 st step

Formation of HMG-CoA MevalonatePathway Acetyl CoA Acetoacetyl CoAHMG 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 pyrophosphateDimethylallyl 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 isoprene unit head tail natural rubber  C C C C.

JOINING ISOPRENE UNITS Head-to-Tail Tail-to-Tail The terms head-to-tail and tail-to-tail are often used to describe how the isoprene units are joined. an extra bond larger terpenoid units dimerize tail-to-tail individual isoprene units join head-to-tail ….. explained later MevalonatePathway

CLASSIFICATION OF TERPENES TYPE OF NUMBER OFISOPRENE TERPENE CARBON ATOMS UNITS hemiterpene terpene sesquiterpene diterpene triterpene tetraterpene C 5 C 10 C 15 C 20 C 30 C 40 one two three four six eight hemi = half di = two sesqui = one and a halftri = three tetra = four NOTE: sesterterpene C 25 five MevalonatePathway

SOME TERPENES (C 10 )  -pinene camphor geraniol menthol rose and other flowerspeppermint camphor treeturpentine MevalonatePathway

SESQUITERPENES guaiazulene geranium oil caryophyllene oil of cloves MevalonatePathway

HOW TERPENES ARE FORMED?

IPP DMAPP C5C10 C15 C20 C5 isopentenyl-PP 3,3-dimethylallyl-PP C10 geranyl-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 H: - NADHNAD + Enz-B: rearrange dimerize TAIL JOINED SYMMETRICALLY TAIL-TO-TAIL UNITS ARE JOINED TAIL-TO-TAIL