Chemistry Reference
In-Depth Information
Figure 10.9
Biosynthesis of PQQ. (
13
), glutamate (protein bound); (
76
), tyrosine (pro-
tein bound); (
77
), PQQ.
this pathway have been studied in considerable detail. The X-ray structure of the
enzyme that catalyzes the final reaction step has been determined, and reaction
mechanisms have been proposed on that basis (45). However, details of the
biosynthetic pathway are still incompletely understood.
10.2.10 Biotin
Biotin (vitamin H, (
6
), Figs. 10.1 and 10.10) acts a cofactor of carboxylases.
It can be produced in bacteria, plants, and some fungi (46). The biosynthetic
pathway involves four steps that start from alanine (
78
) and pimeoyl-CoA (
79
).
Carboxylation and cyclization of (
81
) affords dethiobiotin (
82
), which is then
converted into biotin (
6
) by the iron/sulfur protein, biotin synthase, in an unusual
radical mechanism (47).
10.2.11 Isoprenoid Cofactors
Isoprenoids are one of the largest classes of natural products that comprise at
least 35,000 reported members (48). Many of these compounds play crucial roles
in human metabolism as hormones, vitamins (vitamins A, D, E and K), quinine-
type cofactors of respiratory chain enzymes (ubiquinone), membrane constituents,
and functionally important side chains of signal cascade proteins (Fig. 10.11).
Chlorophyll (
17
, Fig. 10.2) and heme a (
18
) have isoprenoid side chains.
Whereas vitamin E (
99
) and vitamin A or its biosynthetic precursor,
β
-carotene, must be obtained by animals from dietary sources, many other
isoprenoids, including the quinone type coenzyme Q family (where individual
representatives differ by the length of their side chains), can be synthesized
de
novo
by vertebrates. 3-Hydroxy-3-methylglutaryl-CoA reductase, the enzyme
that catalyzes the conversion of (
S
)-3-hydroxy-3-methylglutaryl-CoA (
84
)to
mevalonate (
85
), is one of the most important drug targets for the prevention of
cardiovascular disease (49, 50).
All isoprenoids are biosynthesized from two isomeric 5-carbon compounds,
isopentenyl diphosphate (IPP), (
86
) and dimethylallyl diphosphate (DMAPP),
(
87
) (Fig. 10.6). The mammalian pathway for the biosynthesis of these key
