Flashcards in Lecture 7: Nucleotide Metabolism Deck (60):
Nucleotides are phosphate __________ of nucleosides
What does a nucleotide contain?
Base, sugar, and a phosphate
Nucleoside = no phosphate
What enzyme makes deoxyribose?
What is the nucleotide abbreviation and nucleoside name for hypoxanthine?
Nucleoside name = inosine
Nucleotide abbreviation = IMP
What is the nucleotide abbreviation and the nucleoside name for xanthine?
Nucleoside name = xanthosine
Nucleotide abbreviation = XMP
CoA, cAMP, NAD and FAD are all examples of what?
What are the sources of ring atoms for purines?
CO2, Gln, Gly, Asp, N10-formyl THF
What are the sources of ring atoms in pyrimidines?
HCO3-, Gln, Asp, N5, N10-methylene THF
___________ are synthesized attached to ribose hostage. The ribose initially contributed by PRPP. The sugar is already there and you want to build the base onto it
What is the committed step of purine synthesis?
Formation of the phosphoribosyl amine (addition of amine group creating PRA)
What is the role of methotrexate?
It inhibits the enzyme that attaches the carbon from the folate to close the purine ring. This will then inhibit DNA synthesis
Where does the ribose-5-phosphate in purine synthesis come from?
What stimulates PRPP synthetase in the first step of purine synthesis?
What inhibits PRPP synthetase in the first step of purine synthesis?
Purine nucleotides (GMP, AMP, IMP)
What stimulates the committed step of purine synthesis?
What inhibits the committed step of purine synthesis?
Purine nucleotides (GMP, AMP, IMP)
What inhibits adenylosuccinate synthetase that converts IMP to adenylosuccinate monophosphate during purine synthesis?
What inhibits IMP dehydrogenase that converts IMP to XMP during purine synthesis?
What step of purine synthesis gives off fumarate?
Adenylosuccinate monophosphate -> AMP with the enzyme adenylosuccinase
What carbon in a purine base is donated from folate, closing the ring structure?
The 8th carbon, next to the amine group donated from glutamine in the committed step
AMP synthesis is stimulated by _______
GMP synthesis is stimulated by ______
__________ are synthesized by building the base first then adding your sugar.
- Synthesized from carbamoyl phosphate and aspartate by ATCase
What stimulates the carbamoyl phosphate synthetase II in the first step of pyrimidine synthesis?
What inhibits Carbamoyl phosphate synthetase II in the first step of pyrimidine synthesis?
What is the regulated enzyme in pyrimidine synthesis and is necessary to build the base?
Aspartate transcarbamoylase (ACTase)
What steps of pyrimidine synthesis occur in the mitochondria?
Dihydroorotate-> orotate with the enzyme dihydroorotate dehydrogenase
**This enzyme only in the mito**
What drug can inhibit thymidylate synthase that converts dUMP -> dTMP in pyrimidine synthesis?
- This is the step in pyrimidine synthesis that utilizes folate
5-fluorouracil is a drug that is an analog of thymidilate synthase which is an enzyme that converts dUMP -> dTMP in pyrimidine synthesis. What is 5-fluorouracil good at curing?
There is a human hereditary disorder involving the synthesis of pyrimidine nucleotides called _______ _________
What is used to treat orotic aciduria?
What feedback inhibits ATCase in pyrimidine synthesis?
What stimulates ATCase in pyrimidine synthesis?
What is the limiting factor for DNA synthesis?
What types of diseases is methotrexate used for?
Methotrexate is an example of what type of inhibitor?
Strong competitive inhibitor
- Very low kM so you have to be careful when prescribing it and give very low doeses
What enzyme does methotrexate target?
Dihydrofolate reductase that converts in the liver
Antibacterial agents such as ______ drugs act as competitive inhibitors of teh bacterial enzyme that incorporates p-aminobenzoic acid (PABA) into folate.
What are sulfa drugs used for?
Used to inhibit the replication of viruses and bacteria
What disease is caused by excess adenosine deaminase, which is the enzyme that converts adenosine -> inosine in purine catabolism?
- You have a buildup of inosine
What disease is caused by deficient levels of adenosine deaminase which is the enzyme that converts adenosine -> inosine in purine catabolism?
- Causes a buildup of adenosine
How does an overproduction of adenosine deaminase cause heymolytic anemia?
Increased degradation of adenosine depletes adenine nucleotide pool and triggers premature destruction of RBCs
What is SCID?
- Fatal genetic disorder in which both B and T cells of the adaptive immune system are defective
Gout most commonly affects the big toe. What is the anatomical name for this?
Metatarsal pharyngeal joint
What is the role of urate oxidase?
Converts uric acid to soluble allantoin
What is the role of colchicine?
A treatment used for gout. It decreases the movement of granulocytes to the affected area
What is the role of probenecid?
Used in the treatment of gout. Increases excretion of uric acid
In pyrimidine catabolism, what pyrimidines make ketogenic products and what are the products?
U's and C's make the ketogenic product malonyl CoA
In pyrimidine catabolism what pyrimidines make glucogenic products and what are the products?
T's make the glucogenic products methylmalonyl CoA and Succinyl CoA
What is the role of uridine phosphorylase?
Converts uridine or deoxyuridine -> Uracil and Deoxythymidine -> thymine in pyrimidine catabolism
How much energy is required to generate IMP in purine synthesis?
**1 more than pyrimidine synthess*
How much energy is required to generate UMP?
What is the role of dihydrofolate reductase?
Convert dihydrofolate (inactive) -> THF (active)
**This is the enzyme that is inhibited by methotrexate**
What is the role of APRT (adenine phosphoribosyl-transferase)?
Used in the purine salvage pathway to convert adenine -> AMP
- Uses PRPP as a cofactor
What is the role of HGPRT?
Used in purine catabolism to convert Guanine and Hypoxanthine -> GMP or IMP
- Uses PRPP as cofactor
What is Lesch-Nyhan syndrome?
Defect in HGPRT enzyme in purine salvage pathway
- Overproduction of uric acid -> Pts have primary hyperuricemia and hyperuricosuria leading to gout
What are the symptoms of Lesch-Nyhan syndrome?
**defect in HGPRT**
Urate kidney stones, poor muscle control, mental retardation and a tendency to self mutilation
What is the pyrimidine salvage pathway for uracil?
Uracil -> uridine with uridine phosphorylase then uridine -> UMP with kinase then UMP -> UDP -> UTP
What is the pyrimidine salvage pathway for thymine?
Thymine -> deoxythymidine using thymidine phosphorylase then deoxythymidine -> dTMP using thymidine kinase then dTMP -> dTDP -> dTTP