BIOCHEMISTRY

Nucleotide Metabolism (TABLES)

IMP SYNTHESIS (CYTOSOLIC AREA OF THE CELL)
STEP REACTION ENZYME CO-ENZYME(s) NOTES

Ribose-5-phosphate
1 Ribose-5-phosphate → Phosphoribosyl pyrophosphate (PRPP)
pyrophosphokinase/PRPP Synthase`
• Activation of Ribose-5-Phosphate
• it must be activated through ATP (donor)
ATP
and PRPP Synthase (Phosphorylation)
Mg
• OH group is replaced by 2 phosphates
(donated by ATP)

• Acquisition of Purine Atom 9

• COMMITED/RATE LIMITING/MOST
CONTROLLED STEP
Glutamine • PRPP Glutamyl Amidotransferase is the
2 PRPP II → β-5-D-phosphoribosylamine PRPP Glutamyl Amidotransferase
H2O RATE LIMITING ENZYME
• Pyrophosphate is replaced with amino
group donated by glutamine
• N9 = Glutamine
Glycine • Acquisition of C4, C5, and N7
3 β-5-D-phosphoribosylamine → Glycinamide ribonucleotide Glycinamide Synthetase
ATP • C4, C5, N7 = donated by glycine
N5, N10-
Glycinamide ribonucleotide → Formylglycinamide ribosyl-5- • Acquisition of C8
4 Formyltransferase Methyltetrahydrofolate
phosphate • Not ATP driven
(N-formyl THF)
• Acquisition of N3
Formylglycinamide ribodyl-5-phosphate → Glutamine
5 VI Synthetase • N3 = donated by Glutamine
Formylglycinamidine ribosyl-5-phoshate ATP
• Where the 1st atom of 2nd ring is made (N3)
ATP • Closure of the 1st ring
Formylglycinamidine ribosyl-5-phoshate → Aminoimidazole
6 VII Synthetase Mg • 1st ring (Imidazole) needs ATP
ribosyl-5-phosphate
• 2nd ring does not need ATP
Aminoimidazole ribosyl-5-phosphate → Aminoimidazole CO2 • Acquisition of C6
7 VII Carboxylase
carboxylate ribosyl-5-phosphate ATP • C6 = donated by CO2
• Acquisition of N1
Aminoimidazole carboxylate ribosyl-5-phosphate → Aspartate
8 IX Synthetase • N1 = donated by Aspartate by amide
Aminoimidazole succinyl carboxamide ribosyl-5-phosphate ATP
condensation reaction
• Elimination of Fumarate
Aminoimidazole succinyl carboxamide ribosyl-5-phosphate → • Nitrogen is retained
9 Adenylsuccinase -
Aminoimidazole carboxamide ribosyl-5-phosphate • Fumarate is produced by removing the
amino group from Aspartate
Aminoimidazole carboxamide ribosyl-5-phosphate → N10-
10 Formyltransferase • Acquisition of C2
Formimidoimidazole carboxamide ribosyl-5-phosphate Formyltetrahydrofolate
• Closure of the 2nd ring
Formimidoimidazole carboxamide ribosyl-5-phosphate →
11 IMP Cyclohydrolase - • No ATP is needed
Inosine monophosphate (IMP)
• H2O is relased
**NOTE: the parts that are bold in the reaction columns are the PRODUCTS.

Uses ATP = 1,3,5,6,7,8 Does not use ATP = 2,4,9,10,11

KAPOKIES 1
 GMP/Guanylate Formation
STEP REACTION ENZYME
1 IMP → Xanthosine monophosphate (XMP) IMP Dehydrogenase + H2O
XMP-Glutamine amidotransferase +
2 XMP → Guanosine monophosphate (GMP)
Glutamine + ATP
AMP/Adenylate Formation
1 IMP → Adenylsuccinate Adenylosuccinate synnthetase
2 Adenylsuccinate → Adenylate (AMP) Adenylosuccinase
NOTES
• H2O replaces C2 of IMP
with O2
• O2 = donated by water
• Glumatime – amino donor
• ATP – replaces O2 with an
amino group
• O2 from water is replaced
with amino acid (from
Glutamine)
• GTP = energy source
• Aspartate = amino donor
• Enzyme is for the removal
of fumarate
• The formation of fumarate
is from the removal of
amino acid from Aspartate
KAPOKIES 2
 OROTIDINE MONOPHOSPATE SYNTHESIS
STEP REACTION ENZYME CO-ENZYME(s)
CPS II
CO2 + Glutamine + ATP → Carbamoyl Phosphate
1 Inhibited by: UPT & CTP
(CAP)
Activated by: ATP & PRPP
Aspartate
Transcarbamoylase
2 CAP → Carbamoyl Aspartate (CAA) Inhibited by: CTP
Activated by: ATP
3 CAA → Dihydroorotic Acid (DHOA) Dihydroorotase
Dihydroorotate Coenzyme Q (oxidizing
4 DHOA → Orotic Acid (OA)
Dehydrogenase
Orotate Phodphoribosyl
5 OA → Orotidine-5’-monophosphate (OMP)
Transferase
6 OMP → Uridine Monophosphate (UMP) OMP Decarboxylase
NOTES
• Synthesis of Carbamoyl
Phosphate
• CPS II = RATE LIMITING
ENZYME
• Condensation of
Glutamine and
- Bicarbonate in the
presence of ATP
• HCO3 = source of Carbon
on the product
• Amino group of Glutamine
= Nitrogen source
• ATP is needed
• Synthesis of Carbamoyl
Aspartate
• no energy input is needed
- • Release of phosphate
• Carbamoyl is retained
• Aspartate is then added
(donates C4, C5, C6, N1)
• Closure of ring
-
• H2O = byproduct
• Oxidation of DHOA to
Orotate
agent)
• NAD is needed
• Acquisition of Ribose
Phosphate Moiety
PPRP
• PPRP: source of ribose
phohsphate
• Decarboxylation of OMP
• CO2 = byproduct
-
• Removal of CO2 > Uracyl >
UMP

KAPOKIES 3