Part 4. Metabolism of Nucleotides Flashcards
How does digestion of DNA and RNA work?
Everything we eat consists of cells, this have DNA and RNA
Meats have more than vegetables or fruits
There is essentially no dietary requirement since our bodies can make and reuse what we make in sufficient quantities
Since we ingest a lot of nucleic acid, our bodies have mechanisms whereby to degrade and utilize the components of nucleic acids
What are the differences between ribonucleotides and deoxyribonucleotides?
What are the differences between nucleotides and nucleosides?
Slide 7 Mar 22
Nucleotide- nitrogenous base, sugar (ribose or deoxyribose), and 1-3 phosphate groups
Nucleoside- nitrogenous base covalently attached to a sugar (ribose or deoxyribose)
What are the purines and pyrimidines?
Purines- adenine and guanine
Pyrimidines- cytosine, thymine, and uracil
What are the 5 functions of nucleotides?
- Precursors of DNA and RNA
ATP, GTP, CTP, UTP -> RNA
dATP, dGTP, dCTP, dTTP -> DNA - ATP- energy currency in biological systems
- Adenine nucleotides - components of 3 major coenzymes (NAD, FAD, Coenzyme A)
Slide 8 Mar 22 - Activated intermediates in many biosynthetic pathways (UDP glucose)
- Metabolic and physiologic regulators (cAMP, adenosine)
What are the two ways purine nucleotides are biosynthesized?
- De novo pathway (starting from beginning)- start with ribose 5 phosphate then build purine ring into that sugar one atom or few atoms at a time
Slide 11-12 Mar 22 - Salvage pathway
Minor and major
Minor- done by adenine phosporibosyltransferase (APRT) enzyme
Major- done by hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
Slide 15 Mar 22
How is purine nucleotide biosynthesis regulated?
- Feedback inhibition by purine nucleotides is major form
- Primary target is the enzyme that catalyzes the first committed step in the pathway, glutamine-PRPP amidotransferase
3 reciprocal regulation of GMP and AMP synthesis
GTP is required for IMP -> AMP
ATP is required for IMP-> GMP
Slide 14 Mar 22
How are purine nucleotides degraded?
Gout
Characterized by high blood levels of uric acid due to overproduction or under excretion of uric acid
Uric acid crystals deposit in joints causing pain and inflammation
Treated by drugs (allopurinol which is a suicide inhibitor) or dietary and alcohol restriction
Slide 2 Mar 25
What is Lesch Nyhan syndrome?
Cause by deficiency in HGPRT activity due to mutations in the gene
X linked disease (primarily affects males)
Very rare
Can’t salvage purines efficiently, thus de novo synthesis increases cause PRPP levels increase since less is co aimed through salvage pathway, IMP and GMP levels drop
These lead to high levels of uric acid production
Slide 6 Mar 25
What is the de novo pathway for pyrimidines?
Synthesize carbamoyl phosphate
Build the pyrimidine ring (orotate)
Link orotate to ribose 5-phosphate
Slide 7 Mar 25
Slide 9 Mar 25
How is carbamoyl phosphate (CP) synthesized?
Rate limiting step on pyrimidine synthesis
Enzyme: carbamoyl phosphate synthetase II (CPS II)
Slide 8 March 25
How are nucleoside mono, di and triphosphates interconverted?
Slide 10 March 25
Enzyme: nucleoside monophosphate kinase
Enzyme: nucleoside diphosphate kinase
How are ribonucleotides reduced to deoxyribonucleotides?
By what enzyme?
Slide 11-12 Mar 25
Enzyme: ribonucleotide reductase
NADPH converts to NADP
How is ribonucleotide reductase (RNR) regulated?
- RNR maintains a balanced supply of dNTPs for DNA synthesis
- Regulation is complex
- Regulatory sites: primary regulation site (activity site)
- dATP
+ ATP
Substrate specificity sure binding of ATP, dATP, dGTP, and dTTP
Slide 13 Mar 25
How is thymidylate biosynthesized?
Slide 5 Mar 27
dTMP=thymidylate
How is dUMP converted to dTMP?
- Methylation of dUMP by 1-C transfer
- THF is regenerated by reduction of dihyfrofolate by dihydrodolate reductase using NADPH
Slide 6 MAr 27
