Flashcards in Nucleotide Metabolism Deck (43):
1. Structural component of DNA AND RNA
2. Carriers of activated intermediates (UDP-glucose)
3. Structural components of coenzymes used in metabolism
4. Secondary messengers in signal transduction (cAMP)
5. Energy (ATP)
6. Regulate pathways (using energy)
Structure of nucleotides
-adenine and guanine
-cytosine, thymine(DNA) and uracil(RNA)
Sugar is nucleotides
Why is DNA more stab,e than RNA?
DAN uses deoxyribose which lacks an oxygen so it is more stable
Difference between nucleotides and nucleoside
Nucleoside: nitrogenous base and sugar
Nucleotides: nucleoside plus a phosphate group
What provides the energy to drive these reaction So?
-anhydride bond links 2 and 3 phosphate on nucleotides
-high energy bond that drives biochemical reactions
-ATP AND GTP
Where does the ribose 5p come from for purine synthesis?
What is a key difference in purine and pyramides metabolism?
Purines directly build the nitrogenous base ONTO the sugar
-pyramides build the base then attach it to the sugar
PRPP synthase in purine metabolism
-catalyze so formation of the activated pentose
Regulation of PRPP SYNTHASE
Activator: inorganic phosphate
Inhibitor: purine ribonucleotides
What is the default of purine nucleotides synthesis?
-produces ribonucleotides(not deoxyribose
What is the rate limiting step of purine synthesis?
PRPP AMIDOTRANSFERASE REGULATION
Activated: PRPP (substrate)
Inhibitors: purine nucleotides(end products)
What does folate do?
-required for subsequent steps as a carbon donor
-active form is THF
What enzyme makes THF
-dihydrofolate reductase turns folate into THF
Who makes their own folate?
-bacteria make their own folate, we cant.
What does THF turn into?
-THF acts as a carbon donor and makes IMP
-IMP can then turn into AMP and GMP
-purine analog that acts as a product inhibitor
-inhibits PRPP amidotransferase
-if base is formed, it will have mutations
-folic acid analog
-inhibits digydrofolate reductase so no THF can be made
-works ONLY IN MAMMALS
-selectively inhibits rapidly dividing cells
-structural analog of para-aminobenzoic acid (PABA)
-competitive inhibitor of bacteria producing folic acid
-bacteria purine synthesis inhibited
What is the rate limiting enzyme for pyrimidine synthesis?
Regulators of CPS II
-activated by PRPP
-Inhibited by UTP(end product)
What are the two amino acids used in nitrogenous base structure of pyrimidines?
-glutamine and aspartate
What does PRPP provide for pyrimidine synthesis?
-ribonucleotides are converted into deoxyribonucleotides
-hydroxyurea inhibits it
-inhibits ribonucleotide reductase
-also treats sickle cell by promoting fetal hemoglobin
convert dUMP into dTMP
-use thymidylate synthase
-anti tumor drug that inhibits thymidylate synthase
what do 5-FU and hydroxyurea target?
-affect production of DNA, but not RNA
-so really good at targeting rapidly dividing cells
-antibiotic that is selective for the prokaryotic version of dihydrofolate reductase
-they are not salvaged to a significant degree
-no high yield disease from breakdown so not important
Why is it important to recycle purines?
-purine bases are more complex than pyrimimdines
-take more steps to make it
-salvaging it is more important because it takes too much energy to make them
salvage pathway of purine general
-base is recovered by removing phosphate and sugar moieties
-this yields hypoxanthine or guanine
-those are shuttled back into synthesis
adenosine deaminase deficiency
-immune system(T and B cells) are primarily affected
-patients are super susceptible to inflection (bubble)
-it cannot be recycled, so youre excreting too much
treatment of SCID
-bone marrow transplant or enzyme replacement
-excretion pathway of purines
-produces uric acid which is then excreted as urine
-result of hyperuricemia
-accummulation of uric acid crystals in the joints
What causes gout?
-overproduction of uric acid
-problem with excretion
-inhibits xanthine oxidase
-helps overproducers of uric acid stop making it
-deficiency in purine salvage pathway
-defect in HGPRT
-you end up excreting like 90%