Flashcards in Nucleotide Metabolism Deck (33):
Nucleoside is :
Nucleotide is :
Base + Sugar
Base + Sugar + Phosphate
Deoxy meaning for nucleotides?
Deoxy doesnt have OH group in bottom right (2nd ) carbon. (In DNA) Oxy has OH group. (In RNA)
ATB Base, Ribose sugar (5 Carbon, Two OH groups on bottom carbons
Purine vs Pyrimidine
Purine 2 ring base, pyrimidine 1 ring base
What are the connector bonds in ATP? (3)
N glycosidic bond between base and sugar, Phosphoric acid ester between sugar and phosphate, phosphoric acid anhydride between phosphates.
Names of Purines? Names of Pyrimidines?
Purines: Adenine, Guanine
Pyrimidines: Thymine(Uracil in RNA), Cytosine
Nucleoside names of Bases? ATGC
Adenosine, Thymidine, Guanosine, Cytidine
What are some roles of Nucleosides and Nucleotides?
ATP, GTP, Co-substrates in many reactions, Cofactor Components, cAMP, cGMP (regulatory roles), Vitamin B 12
Source of ring atoms for Purines?
Source of ring atoms fo Pyrimidines?
CO2, Gln, Gly, Asp, N10-formyl THF
HCO3-, Gln, Asp, N5, N10-methylene THF
What type of molecules are Hypoxanthine and Xanthine/
What are their Nucleoside names?
What is created in PPP?
Ribose 5 Phosphate, 2 NADH
What does Methotrexate prevent? How does it do this?
Oxidation of NADPH by DHFR. This will stop the production of Purine Synthesis. Used as an anti-cancer drug.
Competitive inhibitor of Folate. Binds to DHFR 100 times more tightly, disrupts DNA replication in rapidly dividing cells.
What are Sulfa drugs and how do they work?
Disrupts bacterial enzyme that Incorporates PABA (p-aminobenzoic acid) into folate. This stops Oxidation of NADPH by DHFR and will disrupt DNA replication selectively in bacteria.
What are the 3 points of feedback inhibition in the Production of Purine nucleotides?
Purine Nucleotides inhibit creation and use of PRPP
IMP to AMP pathway inhibited by AMP
IMP to GMP inhibited by GMP
How is the Purine production pathway cross regulated?
AMP Synthesis is stimulated by GTP
GMP Synthesis is stimulated by ATP
What is converted into AMP and GMP?
What are the two purine salvage pathway enzymes?
HGPRT (Hypoxanthine guanine phosphoribosyl transferase)
APRT (Adenine Phosphoribosyl Transferase)
What is the commited step in Purine synthesis?
Creation of the Phosphoribosyl Amine
What are the 4 steps in purine synthesis?
Ribose 5P activation
Convert PRP to PRA (Phosphoribosylamine)
Construct IMP ring
Convert IMP to adenosine an dguanosine deoxynucleotides
For Purines and Pyrimidines, which comes first, Sugar attachment or Ring formation
Purines: Sugar ----> Ring attachment
Pyrimidines: Ring --->Sugar
Carbamoyl Phosphate + Aspartate ---> Formation of n-Carbamoyl Aspartate ----> Fabrication of Orotate Ring ----> ______.
Which of these is the commited step?
The formation of n-carbamoyl aspartate is the commited step
What are the three steps in Pyrimidine synthesis?
1. Fabrication of orotate ring
2. Atach PRPP to form UMP
3. Convert UMP to uridine, cytosine, and thymidine (deoxy)nucleotides
What is the anticancer agent that inhibits thymidylate synthase, stopping pyrimidine production?
5-fluoroacil (aka Adrucil)
This stops production of DNA. An anticaner agent.
What are the two major regulatory points in pyrimidine ?
Which one occurs only in bacteria?
Carbamoyl Phosphate Sythetase inhibited by UTP, stimulated by PRPP
Aspartate Transcarbamoylase (ATCase) is feedback inhibited by CTP (BACTERIA ONLY)
What is Orotic Aciduria?
How do you treat?
Problem with UMP synthase step in pyrimidine synthesis.
Treat with oral uridine
What is Acyclovir? How does it work? What is it used to treat?
Molecule that looks like Guanine Nucleoside, it gets phosphorylated by Thymidine kinase to look like acyclo GMP, gets converted by other enzymes to acyclo GTP, inhibits the Viral DNA Polymerase.
Chickenpox and herpes lesions
In the degradation of Nucleotides, what do the following do?
Ribonucleases and Deoxyribonucleases
Convert RNA and DNA to short Oligomers
Convert Short oligomers to NMPs or dNMPS (nucleotides)
Convert NMP and dNMP to nucleosides and deoxynucleosides
Removes ribose group, left at just purine or pyrimidine
What disease does increased Adenosine Deaminase cause? How does it do so?
Causes hemolytic anemia, increased degradation of adenosine, premature destruction of RBCs
What disease does underproduction of Adenosine Deaminase cause?
Severe combined Immunodeficiency (SCID)
(second most common form)
What is the symptom of Gout?
Where is the most commonly affected area?
Historically, a disease of the ____?
Describe the crystals and the inflamatory response
Big toe (metatarsal pharangeal joint)
Disease of the wealthy
Uric acid= weak acid, deprotonates in normal conditions, combine with Na ions, Monosodium urate crystals precipitate.
In pyrimidine Nucleotide Catabolism:
What does Uracil get converted to? What does this feed into?
What does Thimine eventually get converted to? What does these products feed into? What is the intermediate product?
Malonyl CoA- Fatty Acid Synthesis
Methylmalonyl CoA and Succinyl CoA - TCA Cycle
What happens in the Pyrimidine Nucleotide Salvage Pathway? What enzyme and inhibitor is present in this pathway for Thymine?
Uracil is converted to UTP.
Thymine is converted to dTTP.
Thymidine Kinase is present in this path, which can be inhibited by Acyclovir.