11. TERPENOIDS: METABOLISM
593
the well-known mevalonic acid (VI). Phosphorylation with ATP leads
to mevalonic acid 5-pyrophosphate (VIII) via the 5-phosphate (VII),
and further reaction with ATP, through the loss of C0 2 and phosphoric
acid, gives isopentenyl pyrophosphate (IX). The further steps beyond
this "active isoprene" are clarified by the interesting results of Lynen
(11-13). According to these, the isopentenyl pyrophosphate is then
isomerized to γ,γ-dimethylallyl pyrophosphate (X) through the enzyme
isopentenyl pyrophosphate isomerase. The formation of this compound
is important, since the carbonium ion is first represented in the allyl
pyrophosphate, whose transformation with the reactive double bond
of the isopentenyl pyrophosphate leads to the C—C linkage of the C 5
units. The geranyl pyrophosphate (XI) thus formed can react with a
further molecule of isopentenyl pyrophosphate to form farnesyl pyrophosphate (XII). Through elimination of the O—P bond with the help
of phosphatase, geranyl pyrophosphate yields geraniol and farnesyl pyrophosphate, farnesol as parent compounds for terpenes and sesquiterpenes, respectively.
Through reduction with TPNH, however, two fai lesyl residues can
combine to form squalene, this being the biogenetic parent compound of
cyclic triterpenes and sterols (cf. Chapter 3, this volume). With the
further incorporation of isopentenyl pyrophosphate, farnesyl pyrophosphate is transformed into geranylgeranyl pyrophosphate, which yields
diterpene combinations on hydrolysis and carotenoids on reductive dimerization and subsequent dehydration. The further synthesis to polyterpene combinations, solanesol (14), terpenoid side chains of ubiquinones, and the K 2 vitamins (15-19), as well as caoutchouc, is illustrated
in Fig. 1. The validity of this scheme could be demonstrated by the isolation of γ,γ-dimethylallyl alcohol, geraniol, farnesol, and probably geranyl
geraniol, as well as the corresponding pyrophosphates (12). Thus the
"biogenetic isoprene rule" of Ruzicka (2-4) is confirmed, according to
which terpenes and terpenoids are derived from the corresponding
regularly constructed aliphatic parent compounds (geraniol, farnesol,
geranylgeraniol, squalene).
Recognition of the "active isoprene" and its precursors makes it possible, through the introduction of tagged intermediate products, to obtain
a clear picture of the biosynthetic pathway of terpene compounds. Thus,
isopentenyl pyrophosphate can be synthesized (11) and, within the
organism, converted into terpene compounds, e.g., through enzymes of
the liver into cholesterol (11), or in the latex of Taraxacum kok-saghyz
(Arreguin, according to reference 11) into radioactive caoutchouc; the
use of radioactive mevalonic acid, however, is much simpler. This precursor is converted to terpene compounds so quickly that one might
593
the well-known mevalonic acid (VI). Phosphorylation with ATP leads
to mevalonic acid 5-pyrophosphate (VIII) via the 5-phosphate (VII),
and further reaction with ATP, through the loss of C0 2 and phosphoric
acid, gives isopentenyl pyrophosphate (IX). The further steps beyond
this "active isoprene" are clarified by the interesting results of Lynen
(11-13). According to these, the isopentenyl pyrophosphate is then
isomerized to γ,γ-dimethylallyl pyrophosphate (X) through the enzyme
isopentenyl pyrophosphate isomerase. The formation of this compound
is important, since the carbonium ion is first represented in the allyl
pyrophosphate, whose transformation with the reactive double bond
of the isopentenyl pyrophosphate leads to the C—C linkage of the C 5
units. The geranyl pyrophosphate (XI) thus formed can react with a
further molecule of isopentenyl pyrophosphate to form farnesyl pyrophosphate (XII). Through elimination of the O—P bond with the help
of phosphatase, geranyl pyrophosphate yields geraniol and farnesyl pyrophosphate, farnesol as parent compounds for terpenes and sesquiterpenes, respectively.
Through reduction with TPNH, however, two fai lesyl residues can
combine to form squalene, this being the biogenetic parent compound of
cyclic triterpenes and sterols (cf. Chapter 3, this volume). With the
further incorporation of isopentenyl pyrophosphate, farnesyl pyrophosphate is transformed into geranylgeranyl pyrophosphate, which yields
diterpene combinations on hydrolysis and carotenoids on reductive dimerization and subsequent dehydration. The further synthesis to polyterpene combinations, solanesol (14), terpenoid side chains of ubiquinones, and the K 2 vitamins (15-19), as well as caoutchouc, is illustrated
in Fig. 1. The validity of this scheme could be demonstrated by the isolation of γ,γ-dimethylallyl alcohol, geraniol, farnesol, and probably geranyl
geraniol, as well as the corresponding pyrophosphates (12). Thus the
"biogenetic isoprene rule" of Ruzicka (2-4) is confirmed, according to
which terpenes and terpenoids are derived from the corresponding
regularly constructed aliphatic parent compounds (geraniol, farnesol,
geranylgeraniol, squalene).
Recognition of the "active isoprene" and its precursors makes it possible, through the introduction of tagged intermediate products, to obtain
a clear picture of the biosynthetic pathway of terpene compounds. Thus,
isopentenyl pyrophosphate can be synthesized (11) and, within the
organism, converted into terpene compounds, e.g., through enzymes of
the liver into cholesterol (11), or in the latex of Taraxacum kok-saghyz
(Arreguin, according to reference 11) into radioactive caoutchouc; the
use of radioactive mevalonic acid, however, is much simpler. This precursor is converted to terpene compounds so quickly that one might