Page 197 - Color Atlas of Biochemistry
P. 197
188 Metabolism
Purine and pyrimidine biosynthesis (1b) and then converted into dihydroorotate
by closure of the ring (1c). In mammals, steps
The bases occurring in nucleic acids are de- 1a to 1c take place in the cytoplasm, and are
rivatives of the aromatic heterocyclic com- catalyzed by a single multifunctional enzyme.
pounds purine and pyrimidine (see p. 80). In the next step (1d), dihydroorotate is oxi-
The biosynthesis of these molecules is com- dized to orotate by an FMN-dependent dehy-
plex, but is vital for almost all cells. The syn- drogenase. Orotate is then linked with phos-
thesis of the nucleobases is illustrated here phoribosyl diphosphate (PRPP) to form the
schematically. Complete reaction schemes nucleotide orotidine 5 -monophosphate
are given on pp. 417 and 418. (OMP). Finally, decarboxylation yields uridine
5 -monophosphate (UMP).
Purine biosynthesis starts with PRPP (the
A. Components of nucleobases
names of the individual intermediates are
The pyrimidine ring is made up of three com- givenon p. 417). Formationof the ring starts
ponents: the nitrogen atom N-1 and carbons with transfer of an amino group, from which
C-4 to C-6 are derived from aspartate, carbon the later N-9 is derived (2a). Glycine and a
-
C-2 comes from HCO 3 ,and thesecondnitro- formyl group from N 10- formyl-THF then sup-
gen(N-3) is takenfrom the amide group of ply the remaining atoms of the five-mem-
glutamine. bered ring (2b, 2c). Before the five-membered
The synthesis of the purine ring is more ring is closed (in step 2f), atoms N-3 and C-6
complex. The only major component is gly- of the later six-membered ring are attached
cine, which donates C-4 and C-5, as well as N- (2d, 2e). Synthesis of the ring then continues
7. All of the other atoms in the ring are in- with N-1 and C-2 (2g, 2i). In the final step (2j),
corporated individually. C-6 comes from the six-membered ring is closed, and inosine
–
HCO 3 .Amide groups from glutamine provide 5 -monophosphate arises. However, the IMP
the atoms N-3 and N-9. The amino group formed does not accumulate, but is rapidly
donor for the inclusion of N-1 is aspartate, converted into AMP and GMP. These reactions
which is converted into fumarate in the proc- and the synthesis of the other nucleotides are
ess, in thesameway as in the urea cycle (see discussed on p. 190.
p. 182). Finally, the carbon atoms C-2 and C-8
10
are derived from formyl groups in N - Further information
formyl-tetrahydrofolate (see p. 108).
The regulation of bacterial aspartate
carbamoyltransferase by ATP and CTP has
B. Pyrimidine and purine synthesis
been particularly well studied, and is dis-
The major intermediates in the biosynthesis cussed on p. 116. In animals, in contrast to
of nucleic acid components are the prokaryotes, it is not ACTase but carbamoyl-
mononucleotides uridine monophosphate phosphate synthase that is the key enzyme in
(UMP) in the pyrimidine series and inosine pyrimidine synthesis. It is activated by ATP
monophosphate (IMP, base: hypoxanthine) in and PRPP and inhibited by UTP.
the purines. The synthetic pathways for pyri- The biosynthesis of the purines is also
midines and purines are fundamentally dif- regulated by feedback inhibition. ADP and
ferent. For the pyrimidines, the pyrimidine GDP inhibit the formation of PRRPP from ri-
ring is first constructed and then linked to bose-5 -phosphate. Similarly, step 2a is in-
ribose 5 -phosphate to form a nucleotide. By hibitedbyAMP andGMP.
contrast, synthesis of the purines starts di-
rectly from ribose 5 -phosphate. The ring is
then built up step by step on this carrier mol-
ecule.
The precursors for the synthesis of the
pyrimidine ring are carbamoyl phosphate,
–
which arises from glutamate and HCO 3 (1a)
and the amino acid aspartate. These two com-
ponents are linked to N-carbamoyl aspartate
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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