Flashcards in Nucleotide Metabolism Deck (42)
What are the components of a nucleotide?
sugar, nitrogenous base, and phosphate group
What are the names of all the nucleotides?
What are the components of a nucleoside?
sugar, nitrogenous base
what are the names of all the nucleosides?
What are the names of the nucleic acids?
Which nucleic acid is the only nucleic acid that is NOT part of DNA?
What are the specific roles/functions of nucleotides and nucleosides in metabolism?
1.) They act as co-substrates for many rxns
2.) They are components of cofactors
3.) Play a regulatory role in cellular signaling (cAMP, cGMP)
4.) Make important biomolecules (Vitamin B12)
What is the order of component addition for De Novo Purine Synthesis?
1.) Sugar Activation
2.) Nitrogenous Base Building
What is the order of component addition for De Novo Pyrimidine Synthesis?
1.) Build the Nitrogenous Base
2.) Add Sugar Ring
What are the sources of the pyrimidine nitrogenous ring?
Asparagine, Glutamate, HCO3-: N5,N10-Methylene THF
What are the sources of the purine nitrogenous ring?
Asparagine, Glutamate, Glycine, N10-Formyl THF, CO2
In order to get to the precursor nucleotide for purine synthesis of AMP + GMP, what is the ATP requirement?
4 ATP/ IMP
In order to get to the precursor nucleotide for pyrimidine synthesis of CMP + TMP, what is the ATP requirement?
Tell me the stages of Purine Anabolism
1.) R-5-P activation--> PRPP
2.) PRPP--> Phosphoribosylamine
2.) Addition of Gln, Asn, Gly, CO2, N5,N10-Methylene THF to create hypoxanthine base to get IMP
3.) IMP--> GMP or AMP
What is the committed step of purine anabolism?
GLUTAMINE: PHOSPHORIBSOYL PYROPHOSPHATE TRANSAMINASE
The activation of the PRPP ring with NH3
What is the name of the TCA intermediate that if fed into the TCA cycle during the creation of AMP?
IMP is converted to Adenylosuccinate Monophosphate through through which enzyme?
What enzyme converts IMP--> XMP?
What enzyme converts Xanthine monophosphate to GMP?
what is the role of a nucleotide reductase in nucleotide anabolism?
It reduces the 2' OH group to a 2' H group which creates a deoxyribonucleic acids.
How does Methotrexate inhibit purine synthesis? What is it?
Methotrexate is an anti-cancer drug that works as a competitive inhibitor to folic acid by competing for DHF reductases active site. This causes decreased production of IMP--> decreased purine synthesis.
Km of Methotrexate --> 100x AFFINITY compared to FOLIC ACID
Why are sulfa drugs like sulfanamides (sulfa drugs) used so heavily for the treatment of a bacterial infection?
Sulfanimides (sulfa drugs) selectively work on bacterial cell processes of THF production by prohibiting the binding of PABA to create folic acid--> stopping cell division through lack of nucleotide synthesis.
What is the idea of cross regulation and how does that pertain to AMP/GMP synthesis?
Cross regulation is the idea that AMP synthesis is regulated by [GTP]. Enzymes like adenylosuccinate synthetase + adenylosuccinase --> (+) GTP
GMP Synthesis via IMP Dehydrogenase & GMP Synthetase IS regulated by ATP.
What is the function of phosphodiesterases?
Cleaves the phosphodiester bonds formed between the 5' Phosphate and the 3' OH groups.
What is the function of nucleotidases?
Cleaves nucleotides--> nucleosides + Pi
What is the function of nucleosidases?
Cleaves nucleosides--> nucleic acid + sugar
What are the names of the enzymes that are very important to purine salvage pathway and how do they work?
HGPRT Enzyme (Hypoxanthine & Guanine)
APRT Enzyme (Adenine)-->
Use PRPP + nucleic acid--> nucleotide + PPi
What is the committed step in Human Pyrimidine Synthesis?
Creation of Carbamoyl P via Carbomyl Synthase II
What is the committed step in Bacterial Pyrimidine Synthesis?
Creation of N-carbamoylaspartate via ATCase (aspartate transcarbamoylase)
What are the major steps in De Novo Pathway for pyrimidine synthesis?
1. ) Build the Orotate Ring in the mitochondria
2.) Add the PRPP to Orotate Ring in the Cytosol
3.) Create UMP in Cytosol as a result--> dTMP, CTP
What enzyme converts UTP--> CTP?
What enzyme converts UDP--> dUDP?
What enzyme converts dUMP--> dTMP?
What is the affect of 5-flourouracil? What is it used for?
5-Florouracil is used as an anti-cancer drug that stops thymidylate synthase from producing dTMP--> STOPS DNA PRODUCTION
What is the affect of acyclovir? What is it used for?
Acyclovir is an antiviral drug used to inhibit thymidine kinase which makes dTMP--> dTDP-->dTTP
what is the function of ribonucleases/ deoxyribonucleases?
Breaks oligonucleotides--> shorter nucleotides sequences
What is Oritic Aciduria and how do you treat it?
Orotic Aciduria is the build up of orotate because a dysfunction in UMP synthase enzyme.
**Causes megalobastic anemia!
It can be compensated by Uridine/UMP supplementation
What is Adenosine Deaminase (ADA)?
ADA is a molecule that reduces AMP-->Adenosine
What happens due to overproduction of Adenosine Deaminase?
Cells do NOT have enough AMP because all the enzymes (ADA) are converting Adenosine to Inosine.
what happens due to underproduction of Adenosine Deaminase?
What is Xanthine Oxidase and how does it relate to GOUT Disease.
Xanthine Oxidase is a purine salvage enzyme that breaks down Hypoxanthine--> Xanthine & Xanthine--> Uric Acid.
The accumulation of Uric Acid causes gout crystals that build up in joints of the big toe and hands.
(METATARSAL PHALYNGEAL JOINT)