BIOC/DENT/PHCY 230 LECTURE 6
Jan 13, 2016
BIOC/DENT/PHCY 230
LECTURE 6
Lecture 6: Nitrogen Metabolism II IAmino acids as a source of nitrogen for biosynthesis ofspecialised compounds and nucleotides
q Understand why amino acids are precursors for specialised compounds and
nucleotides.q Be familiar with the notable features of de novo biosynthesis of purines and
pyrimidines.q Be aware of the benefits of nucleotide salvage pathways.q Note the very different end products of purine and pyrimidine degradation.q Know that the product from purine degradation is uric acid and why it can cause
medical problems.q Explain some of the benefits to medicine of understanding nitrogen metabolism.
Nucleotides
found in DNA and RNA
used for energy (ATP and GTP)
building blocks for coenzymes (NADH)
Building blocks for nucleotides
Two classes of bases
Two types of ribose
Synthesis of nucleotides
nucleotide bases can be recycled or synthesised de novo
purine bases are synthesised on ribose
pyrimidine bases are synthesisedindependent of ribose
AMP
Synthesis of PRPP
PRPP contributes ribose phosphate to nucleotides
formation catalysed by PRPP synthetase
PRPP synthetase is allosterically inhibited by AMP, ADP and GDP.
De novo purine synthesis
Glutamine donates an amide to initiate purine synthesis
A whole glycine is added to the nitrogen
The coenzyme tetrahydrofolate donates a formyl group
Glutamine donates a second amide
Imidazole ring is closed in an energy dependent reaction
Aspartate is added in an energy dependent reaction
This is analogous to the urea cycle
Tetrahydrofolate donates a second formyl group
Ring closure
Origins of purine base
IMP can be converted to GMP and AMP
De novo pyrimidine synthesis
The pyrimidine base is synthesised before being attached to ribose
ring closure and oxidation
Ribose is now added via PRPP
UMP can be used to synthesise CTP
Origins of pyrimidine base
purines pyrimidines
Basesynthesis on ribose free
Amino acids gln(2), asp, asp
gly
Other molecules formate(2)carbamoyl
HCO3- phosphate
ATP 5 2
(AMP,GMP)
(UMP)
CMP
gln
3
Comparison of purine and pyrimidine biosynthesis
Ribonucleotides are used as precursors for deoxyribonucleotides
ATP dATP
GTP dGTP
CTP dCTP
UTP dUTP
Ribonucleotide reductase
Thymidine nucleotides are derived from dUMP
Tetrahydrofolate donates a methyl group
Degradation of pyrimidine nucleotides
CTP UTP
-alanine, NH3, CO2
Degradation of purine nucleotides
Free ammonia is also produced in muscle
during severe muscle activity
ATP ADP + Pi
2ADP ATP + AMP
AMP IMP + NH4+
AMP deamina
se
Degradation of purine nucleotides
GOUT
uric acid is quite insoluble
excess uric acid can crystallise in joints
gout can be treated with allopurinol
allopurinol is a competitive inhibitor of
xanthine oxidase
The take home message
nucleotides have a number of functions
they can be synthesised de novo if required
some steps are analogous with the urea cycle
amino acids provide many of the components
synthesis is regulated by the concentrations of
various nucleotides
synthesis is energetically expensive
the degradation of excess purines can cause
gout