bioc/dent/phcy 230 lecture 6. nucleotides o found in dna and rna o used for energy (atp and gtp) o...
TRANSCRIPT
![Page 1: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/1.jpg)
BIOC/DENT/PHCY 230
LECTURE 6
![Page 2: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/2.jpg)
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.
![Page 3: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/3.jpg)
Nucleotides
found in DNA and RNA
used for energy (ATP and GTP)
building blocks for coenzymes (NADH)
![Page 4: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/4.jpg)
Building blocks for nucleotides
![Page 5: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/5.jpg)
Two classes of bases
![Page 6: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/6.jpg)
Two types of ribose
![Page 7: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/7.jpg)
Synthesis of nucleotides
nucleotide bases can be recycled or synthesised de novo
purine bases are synthesised on ribose
pyrimidine bases are synthesisedindependent of ribose
![Page 8: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/8.jpg)
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.
![Page 9: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/9.jpg)
De novo purine synthesis
Glutamine donates an amide to initiate purine synthesis
A whole glycine is added to the nitrogen
![Page 10: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/10.jpg)
The coenzyme tetrahydrofolate donates a formyl group
Glutamine donates a second amide
![Page 11: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/11.jpg)
Imidazole ring is closed in an energy dependent reaction
![Page 12: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/12.jpg)
Aspartate is added in an energy dependent reaction
This is analogous to the urea cycle
![Page 13: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/13.jpg)
![Page 14: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/14.jpg)
Tetrahydrofolate donates a second formyl group
Ring closure
![Page 15: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/15.jpg)
Origins of purine base
![Page 16: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/16.jpg)
IMP can be converted to GMP and AMP
![Page 17: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/17.jpg)
De novo pyrimidine synthesis
The pyrimidine base is synthesised before being attached to ribose
![Page 18: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/18.jpg)
ring closure and oxidation
![Page 19: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/19.jpg)
Ribose is now added via PRPP
![Page 20: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/20.jpg)
UMP can be used to synthesise CTP
![Page 21: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/21.jpg)
![Page 22: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/22.jpg)
Origins of pyrimidine base
![Page 23: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/23.jpg)
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
![Page 24: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/24.jpg)
Ribonucleotides are used as precursors for deoxyribonucleotides
ATP dATP
GTP dGTP
CTP dCTP
UTP dUTP
Ribonucleotide reductase
![Page 25: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/25.jpg)
Thymidine nucleotides are derived from dUMP
Tetrahydrofolate donates a methyl group
![Page 26: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/26.jpg)
Degradation of pyrimidine nucleotides
CTP UTP
-alanine, NH3, CO2
![Page 27: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/27.jpg)
Degradation of purine nucleotides
![Page 28: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/28.jpg)
Free ammonia is also produced in muscle
during severe muscle activity
ATP ADP + Pi
2ADP ATP + AMP
AMP IMP + NH4+
AMP deamina
se
![Page 29: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/29.jpg)
Degradation of purine nucleotides
![Page 30: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/30.jpg)
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
![Page 31: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/31.jpg)
![Page 32: BIOC/DENT/PHCY 230 LECTURE 6. Nucleotides o found in DNA and RNA o used for energy (ATP and GTP) o building blocks for coenzymes (NADH)](https://reader035.vdocuments.us/reader035/viewer/2022070410/56649f125503460f94c2555a/html5/thumbnails/32.jpg)
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