section 27.9
Biosynthesis of Pyrimidine Nucleotides
639
ATP
C 0 2
G lutam ine
©
O
il
,
NH — C — OPO,
OOC
^CH
2
h q J - +n h 3
COO"
Carbamoyl
Aspartate
phosphate
P,
~oocv
HjN
CH,
H20
O
'
'N'
H
COO
Carbam oyl
Dihydroorotate
aspartate
UMP
Orotidine 5"-monophosphate
F IG U R E 2 7 -2 6
De novo
pathway of uridine-5'-monophosphate (UMP) synthesis. Enzymes: (1) carbamoyl phosphate synthetase II;
(2) aspartate transcarbamoylase; (3) dihydroorotase; (4) dihydroorotate dehydrogenase; (5) orotate
phosphoribosyltransferase; (6) orotidine-5'-monophosphate decarboxylase (orotidylate decarboxylase).
rapidly channeled without dissociation from the
polypeptide. Other pathways in eukaryotic cells, such
as fatty acid synthesis, occur on multifunctional
polypeptides.
MITOCHONDRION
Dihydroorotate
O rotate
CYTO PLASM
G lutam ine
H CO f
2ATP
H.O
F IG U R E 2 7 -2 7
Schematic representation of the intracellular location of the six enzymes of
UMP biosynthesis in animals. Pyr 1-3 = 1, Carbamoyl phosphate
synthetase II; 2, aspartate transcarbamoylase; 3, dihydroorotase
4, dihydroorotate dehydrogenase; Pyr 5,6 = 5, orotate
phosphoribosyltransferase; 6, orotidine-5'-monophosphate decarboxylase.
4. Conversion of dihydroorotate to orotate is catalyzed
by dihydroorotate dehydrogenase, a
metalloflavoprotein that contains nonheme-iron atoms
and flavin adenine nucleotides (FMN and FAD). In
this reaction, the electrons are probably transported
via iron atoms and flavin nucleotides that are
reoxidized by NAD+.
5. Biosynthesis of purine and pyrimidine nucleotides
requires carbon dioxide and the amide nitrogen of
glutamine. Both use an amino acid
“nucleus”—glycine in purine biosynthesis and
aspartate in pyrimidine biosynthesis. Both use PRPP
as the source of ribose
1
-phosphate.
6
. UMP is converted to UTP by uridylate kinase and
nucleoside diphosphate kinase.
uridylate kinase
.
_
UMP + ATP ,
- UDP + ADP
nucleoside diphosphate kinase
UDP + ATP ,
^ UDP + ADP
Formation of Other Pyrimidine Nucleotides
UMP is the parent compound in the synthesis of cytidine
and deoxycytidine phosphates and thymidine nucleotides
(which are deoxyribonucleotides).
