PYRIMIDINE METABOLISM

O O O
O

=
- C C

=
COO - C OO C C
H2 N+ CH2 HN CH2 HN CH HN CCH 3
CH HN CCH 3
CH
H2 N CH 2 O O
CHCOO- O=C CHCOO- C.COO-
CHCOO- CHONDR O=C C.COO -

=
O=C O=C O=C CH
O=C
H2N N N ITO I N N N
H H H P-O-CH 2 O P-O-CH 2 O

M
P-O

A
O O O O

O O

HCO3- H2O 2ATP 2ADP P i Glutamate P H2O PPi

BIOSYNTHESIS

Aspartate UQ UQH2 PRPP H H CO 2 H H

PYRIMIDINE

i
H H H H
1.3.1.14 OH OH OH OH
Glutamine Carbamoyl- P Carbamoylaspartate Dihydroorotate Orotate Orotidine- P Uridine -5-P
6.3.5.5 Trifunctional 2.1.3.2 Enzyme 3.5.2.3 M IT
O C HON D RIA
2.4.2.10 Bifunctional Enzyme 4.1.2.3 UMP
ATP PRPP

RNA DNA
O NH 2
RNAn+1 NH 2
C DNAn+1 O ENZYMES
C
TRIPHOSPHATES

C 2.7.7.7 C
N CH 2.7.7.7
NUCLEOSIDE

HN CH 2.7.7.6 2.7.7.6 N CH HN CCH3 1.2.1.18 Malonate semialdehyde

O=C CH RNAn O=C CH DNAn O=C CH
dehydrogenase (acetylating)
O=C CH N 1.3.1.2 Dihydropyrimidine dehydrogenase
N I
N N
Ribose- P-O-P-O-P Ribose-P- O- P -O- P Deoxyribose- P-O- P-O- P Deoxyribose-P-O-P-O-P (NADP+)
6.3.4.2
Uridine triphosphate Deoxycytidine triphosphate Thymidinetriphosphate 1.3.1.14 Orotate reductase (NADH)
Cytidine triphosphate 1.6.4.5 Thioredoxin reductase (NADPH)
UTP ATP CTP dCTP dTTP 1.17.4.1 Ribonucleoside-diphosphate
Glutamine Pi Glutamate ADP + + reductase (NADPH)
O NADP NADPH+H H2O O
C NH 2 ADP NH 2 C 2.1.1.45 Thymidylate synthase
H2O ADP C H2O 3.6.1.15 HN CCH H 2O ADP 2.1.3.2 Aspartate carbamoyltransferase
DIPHOSPHATES

CH ADP 2.7.4.6 C
HN 3
NUCLEOSIDE

2.7.4.6 N CH 1.6.4.5 Pi N CH 3.6.1.15

3.6.1.15 3.6.1.15 2.7.4.6 ATP O=C CH 2.7.4.6 2.3.2.23 Deoxyuridine phosphorylase
O=C CH Pi ATP O=C CH Pi ATP O=C CH N Pi ATP 2.4.2.- Pentosyltransferase
N P- O-P- O-CH 2 N N
(S-S) P- O-P-O-CH 2 Deoxyribose-P-O-P 2.4.2.2 Pyrimidine-nucleoside phosphorylase
Ribose- P - O- P (2SH) Deoxycytidine Thymidine diphosphate 2.4.2.3 Uridine (pyrimidine) phosphorylase
Uridinediphosphate H H Cytidinediphosphate hio diphosphate H H 2.4.2.4 Thymidine phosphorylase
o xi

T
H
dTDP

n
H red H H
UDP OH OH CDP 1.17.4.1 dCDP dTMP 2.4.2.9 Uracil phosphoribosyltransferase
OH H O 2.4.2.10 Orotate phosphoribosyltransferase
O C 2.4.2.23 Deoxyuridine phosphorylase
NUCLEOSIDES MONOPHOSPHATES

H2O THF H 2O ADP

C ADP H2O ADP H2O ADP N CH 2.6.1.18 3-Alanine-pyruvate transaminase
NUCLEOSIDE

HN CH 3.6.1.6 2.7.4.4 3.6.1.6 3.6.1.6 2.7.4.4

NH 2 3.6.1.6 2.7.4.4 NH 2 2.7.4.4 O=C CH 5 10
N N - Methylene- O 2.6.1.22 3-Amino-2-methylpropionate
Pi Pi

=
O=C CH ATP C Pi ATP C Pi ATP N H4Folate ATP C transaminase
N HN CH N CH Deoxyribose-P Dihydrofolate HN CCH 2.7.1.21 Thymidine kinase
3
Ribose-P Deoxycytidine-P 2.7.1.48 Uridine kinase
Uridine-P O=C CH Cytidine-P O=C CH Deoxyuridine-P Thymidine-P O=C CH
2.7.1.74 Deoxycytidine kinase
N N N
UMP Ribose-P CMP Deoxyribose-P dCMP dUMP 2.1.1.45
dTMP Deoxyribose-P 2.7.4.4 Nucleoside-phosphate kinase
PPi 3.5.4.12 2.7.4.6 Nucleoside-diphosphate kinase
2.4.2.9 H2O ADP 3.1.3.31 Nucleotidase
H 2O NH4+ H 2O
i

NH 2 ADP ADP
PYRIMIDINE

O
H2O ADP PRPP C 3.1.3.31 NH 2 H2O ADP 3.1.3.31
2.7.1.48 H 2O 3.5.1.6 3-Ureidopropionase
C 2.7.1.74 C 2.7.1.48
CH Pi 3.1.3.31 ATP O 3.5.2.2 Dihydropyrimidinase
SALVAG

SALVAG

HN CH 3.1.3.31 2.7.1.48 HN N CH 2.7.1.74 Pi 3.1.3.31

ATP C ATP O 3.5.2.3 Dihydroorotase
Pi ATP Pi ATP Pi C
O=C CH
-
O=C CH O=C CH HN CH 3.5.4.1 Cytosine deaminase
N HN CCH
N N 3
-
O=C CH 3.5.4.5 Cytidine deaminase
E

3.5.4.5 Ribose Cytidine ThymidineO=C CH

Ribose Uridine Ribose Deoxycytidine Deoxyuridine N -
N 3.5.4.12 dCMP deaminase
NH 2 3.5.4.14 Deoxyribose 3.5.4.14 Deoxycytidine deaminase
O Pi C Pi
Deoxyribose
3.6.1.6 Nucleoside-diphosphatase
C
NH4+
2.4.2.3 Pi CH H2O
N PPi O
NH4+
HN CH 2.4.2.4 3.6.1.15 Nucleoside-triphosphatase
Ribose-1-P H2O

=
2.4.2.3 C
BASES

O=C CH 2.4.2.9 Ribose-1-P 4.1.1.23 Orotidine-5-phosphate

O=C CH CCH3
N Ribose-1-P N Deoxyribose-1-P Pi HN decarboxylase
H PRPP 6.3.4.2 CTP synthase
H 3.5.4.1 O=C CH
Uracil Cytosine 2.4.2.3 Thymine N 6.3.5.5 Carbamoylphosphate synthase
H (glutamine-hydrolysing)

COO - - O NADPH+H+
COO
C
H2N C
NAD(P)H CH 2 CH 2 CH 2
NAD(P) HN
O=C 1.3.1.2 1.3.1.2
CO 2 HSCoA CH 2 CH 2 O=C CH 2
- - H 2N N
CH 3 COO OHCCH 2COO N
2.6.1.18 3.5.1.6 H H
DEGRADATION

Acetyl-CoA Malonate 3--Alanine 3-Ureidopropionate Dihydrouracil NADP+

PYRIMIDINE

1.2.1.18 -
semialdehyde COO COO
-
O
C C C
C
CHCH 3 H2N CHCH 3 HN CHCH 3
CH3 Alanine Pyruvate NH 3 CO 2 H2O
- - - CH 2 O=C CH 2 O=C CH 2
OOCCH 2 CH 2 COO OHCCHCOO H 2N N N N
H H
Succinyl-CoA Methylmalonate 2.6.1.22 3-Aminoisobutyrate 3-Ureidoisobutyrate Dihydrothymine
3.5.1.6
semialdehyde

Designed by Donald Nicholson c 2002 IUBMB