nucleotides Flashcards
Which of the following is NOT a nucleoside?
A. Adenosine
B. Uridine
C. Cytosine
D. Guanosine
E. Inosine
C. cytosine
nucleoside?
ribose+nucleobase
nucleotide
nucleoside+phosphate
De novo synthesis of purine bases
-makes purine bases from scratch
-utilizes amino acids as carbon and nitrogen donors
-costly in terms of energy: uses ATP in many steps
-PRPP is key starting material
The first step in synthesis of purine base is the _____ and is ________ regulated
-commitment step
-highly regulated
What is a common intermediate for both AMP and GMP synthesis
IMP
The commitment step for de novo purine synthesis is ______ by AMP and GMP as well as IMP
supresses
PRPP _____ the commitment step.
stimulates
____ and _____ suppress their synthesis from IMP
AMP and GMP
GDP and GTP are produced from GMP using
ATP as a _____
phosphate donor.
Salvage pathway
-Hypoxanthine-guanine phosphoribosyl transferase (HGPRTase)
-Adenine phosphoryl transferase (APRTase)
-Pyrimidine phosphoryl transferase
De novo synthesis of pyrimidine bases
-Orotate is synthesized from amino acids and HCO 3-.
-OMP is synthesized from orotate and PRPP, which is
analogous to the salvage pathway.
-UDP and UTP are produced from UMP using ATP as a
phosphate donor.
-CTP is produced from UTP.
Hypoxanthine-guanine phosphoribosyl transferase (HGPRTase)
-hypoxanthine + PRPP ⇄ IMP + PP i
-guanine + PRPP ⇄ GMP + PPi
Adenine phosphoryl transferase (APRTase)
adenine + PRPP ⇄ AMP + PP i
adding phosphate groups
-Both de novo synthesis and salvage pathways generate nucleoside monophosphate
(NMP).
-Nucleotide kinases add phosphate groups to NMP and NDP.
-ATP is the major phosphate donor.
degradation of purine bases
-Purine nucleoside phosphorylase
removes nucleobases from nucleosides.
-The end product of purine nucleobases is
uric acid.
uric acid
-Uric acid is not so soluble.
-May form needle-like sodium urate crystals
-Deposition of sodium urate crystals in joints
causes gout
gout
-Patients show elevated levels of uric acids (hyperuricemia).
-Causes
(Overproduction of purine bases by de novo synthesis, Decreased excretion of uric acid, Alcohol and high-fructose diet)
gout and allopurinol
-Structural isomer of hypoxanthine
-Xanthine oxidase inhibitor
-Reduces the production of uric acid.
-Increases the utilization of hypoxanthine through the
salvage pathway, which reduces de novo purine
synthesis
synthesis of depxyribose nucleotides
-dNTP is necessary for DNA replication and repair.
-Ribonucleotide reductase converts NDP to dNDP, which is the rate-limiting
step for dNTP synthesis.
-Ribonucleotide reductase is allosterically regulated by many NTPs and dNTPs.
-NADPH is used as a reducing cofactor.
synthesis of thymine
-DNA contains thymine instead of uracil.
-Thymidylate synthase converts dUMP to dTMP.
-N 5,N 10-methylene tetrahydrofolate (THF) acts as the methyl donor.
synthesis of NAD+
-Nicotinamide adenine dinucleotide
-Nicotinamide is a vitamin (niacin; vitamin B 3).
-The first step is analogous to the salvage pathway in which PRPP acts as a ribose 5-phosphate donor.
6-mercaptopurine (6-MP)
-antitumor drug
-converted to a mononucleotide through the salvage pathway
-The mononucleotide is a potent negative regulator of PRPP-amidotransferase, the
enzyme catalyzing the commitment step of de novo purine synthesis.
-Metabolized to 6-thiouric acid by xanthine oxidase
_____ and ____ are used together to potentiate the drug activity by inhibiting degradation.
allopurinol and 6-mercaptopurine (6-MP)
5-fluorouracil
-Antitumor drug
-Analog of uracil
-Converted to FUMP and FdUMP in cells
-FUMP is incorporated into RNA and interferes with RNA processing.
FdUMP inhibits _________ irreversibly by forming a covalent bond.
thymidylate synthase
Without dTTP, cells undergo ________, whose mechanism is not well known yet.
“thymineless death”
acyclovir
-Antiviral drug used to treat herpes simplex virus
(HSV) infections
-Converted to the monophosphate by a HSV-
thymidine kinase, which exists only in the infected
cells.
-The triphosphate is used as a substrate for the
HSV DNA polymerase, causing chain
termination
______an esterifed version of acyclovir with valine, is a prodrug with a greater oral
bioavailability.
valacyclovir
sofosbuvir (sovaldi)
-Antiviral drug used to treat hepatitis C
-Prodrug; rapidly converted to the active agent in vivo.
-Activation of the corresponding nucleoside is much slower.
-The active agent is a potent inhibitor of NS5B, which is a RNA-dependent RNA
polymerase
