Mevalonate Pathway Terpenes & Steroids

1. Philippine Normal UniversityTaft Avenue, Manila Mevalonate PathwayTerpenes & Steroids Reyes, Patrick A. BS Chemistry for Teachers

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

3. MevalonatePathway 1st step

4. Formation of HMG-CoA MevalonatePathway HMG CoASynthase Acetyl CoA AcetoacetylCoA HMG CoA

5. Formaton of Mevalonate MevalonatePathway HMG CoAReductase Mevalonate HMG CoA

6. Formation of 5-phosphomavalonate MevalonatePathway Mevalonatekinase Mevalonate 5-phosphomevalonate

7. Formation of 5-pyrophospomevalonate MevalonatePathway PhosphomevalonateKinase 5-phosphomevalonate 5-pyrophosphomevalonate

8. Formation of IPP MevalonatePathway Mevalonate-5-pyrophosphate decarboxylase 5-pyrophosphomevalonate 3-isopentyl pyrophosphate

9. Formation of DMAPP MevalonatePathway Isopentyl pyrophosphate isomerase 3-isopentyl pyrophosphate Dimethylallyl pyrophosphate These five carbons are responsible for formation af all terpenes

10. MevalonatePathway TERPENES

11. Terpenes MevalonatePathway • Terpenes are derived biosynthetically from units of  isoprene natural rubber head . C D tail C C C C isoprene isoprene unit

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

13. MevalonatePathway CLASSIFICATION OF TERPENES TYPE OF NUMBER OF ISOPRENE TERPENE CARBON ATOMS UNITS one hemiterpene C5 two terpene C10 sesquiterpene C15 three diterpene C20 four sesterterpene C25 five triterpene C30 six eight C40 tetraterpene NOTE: hemi = half di = two sesqui = one and a half tri = three tetra = four

14. MevalonatePathway SOME TERPENES (C10) geraniol menthol rose and other flowers peppermint camphor a-pinene camphor tree turpentine

15. MevalonatePathway SESQUITERPENES guaiazulene geranium oil caryophyllene oil of cloves

17. MevalonatePathway HOW TERPENES ARE FORMED?

18. CONCATENATION OF C5 (ISOPRENE) UNITS DMAPP IPP C5 C10 HEAD :B C5 isopentenyl-PP 3,3-dimethylallyl-PP C10 TAIL geranyl-PP C15 C20 C15 farnesyl-PP C20 again geranyl-geranyl-PP EACH NEW UNIT IS JOINED HEAD-TO-TAIL

19. DIMERIZATION OF C15 AND C20 UNITS TAIL rearrange TAIL dimerize Enz-B: H:- NADH NAD+ JOINED SYMMETRICALLY TAIL-TO-TAIL UNITS ARE JOINED TAIL-TO-TAIL