module 13- nucleotide metabolism Flashcards
dietary nucleic acids are degraded & absorbed as
nucleosides
what 2 pathways can purine nucleotides be synthesized?
de novo or salvage
lesch-nyhan syndrome
genetic defect in purine salvage pathway = lot of de novo pathway, stops HGPRT coding, affects males, neuro symptoms
what causes gout
elevation of uric acid= crystals
pyrimidine ring is assembled & attached to
ribose sugar
some anti-cancer & anti-viral therapeutics inhibit
nucleotide metabolism
how are thymidine deoxynucleotides synthesized
methylation reaction
ribonucleotide reductase uses ( ) as reducing agent to convert ribonucleotides to deoxyribonucleotides
NADPH
nucleases- what do they do & what do they produce
hydrolyze phosphodiester bonds, produce monophosphate nucleotides
phosphatases
removes phosphate groups
nucleosidases
hydrolyze link between sugar & nitrogenous base
nucleotides vs nucleosides
tides have phosphate group
where do most of the nucleosides get absorbed
enterocyte
T or F: most nucleosides are further degraded after being absorbed
T
where do most of nucleotides that we need for nucleic acid synthesis come from
biosynthetic pathways not dietary sources
what do nucleotides consist of
nitrogenous base, ribose sugar & phosphate groups
ribose vs deoxyribose
ribose has -OH group and deoxyribose has -H group
is ATP a nucleotide
yes
ATP bonds
anhydride
adenine-based nucleotides are components of what 3 coenyzmes?
NAD, FAD & CoA
how do nucleotides form activated substrates
linking to other biomolecules
T or F: some nucleotides & nucleosides are cellular & physiological regulators
T
adenosine affect on heart
decreases heart rate & decreases force of contraction
de novo pathway
start with ribose 5-P & build purine ring on it to form nucleotides
T or F: amino acids are important contributors of the atoms in the purine ring
T
what are 5 contributors to the purine ring
aspartate, formate, glutamine, glycine & CO2
how to make ribose 5-P reactive (2)
1) ATP is used to form PRPP
2) IMP is precursor for AMP & GMP
what is the regulatory enzyme of nucleotide synthesis
glutamine-PRPP amidotransferase
T or F: ATP is not required to make a nucleotide, uses GTP instead
T
IMP can be used to make ( ) or ( )
AMP or GMP
how to form AMP
aspartate donates amino group
how to form GMP
glutamine donates amino group
how is the de novo pathway inhibited
allosteric inhibition of glutamine-PRPP amidotrasferase by IMP, AMP & GMP (end products of pathway)
what 2 inhibition pathways are used in the de novo pathway
concerted & sequential
what does IMP do during sequential inhibition
inhibits glutamine-PRPP amidotransferase
salvage pathway
joins free purine bases together
what are the 3 purines that are salvaged
adenine, guanine & hypoxanthine
hypoxanthine results from what
deamination of adenine
what does the APRT enzyme form
AMP
what is the major vs minor enzymes in the salvage pathway
minor- APRT
major- HGPRT (hypoxanthine-guanine)
treatment of gout
limiting purine consumption- meat & beer
allopurinol
inhibits uric acid production
uracil, cytosine & thymine are made
de novo
what 3 components are required for pyrimidine backbone
glutamine, aspartate & CO2
what is the regulatory enzyme of pyrimidine synthesis
carbamoyl phosphate synthease II
what are the 4 precursors for pyrimidines
ribose 5-P, CO2, glutamine & aspartate
what is enzyme CPS II inhibited by
UTP
CPS I vs CPS II - process, location, N donor & regulatory effectors
CPS I- urea synthesis, mitochondrial matrix, NH4, stimulates N-acetylGlu & arginine
CPS II- pyrimidine synthesis, cytosol, glutamine, inhibits UTP & stimulates ATP & PRPP
the 1st committed stop in pyrimidine synthesis is catalyzed by
ATCase
ATCase is allosterically inhibited by
CTP
what is the start vs end of pyrimidine synthesis
starts with ASP + CP, CTP is end product
pyrimidine synthesis steps
ASP + CP -> orotate -> OMP -> UMP -> UDP -> UTP -> CTP
substrates for DNA & RNA synthesis
nucleotide triphosphates
nucleoside monophosphate kinases are specific for the ( ) but not the ( )
base, ribose sugar
where does ATP come from
oxidative phosphorylation in the mitochondria or glycolysis
deoxyribonucleotides are synthesized from nucleoside diphosphate molecules by a reduction reaction carried out by what enzyme?
ribonucleic reductase
4 substrates for ribonucleic reductase
ADP, GDP, CDP & UDP
the source of reducing equivalents for the synthesis of deoxyribonucleotides comes from
NADPH from pentose phosphate pathway
ribonucleoside reductase complex
multi-subunit enzyme that is allosterically regulated
how is the proper balance of deoxyribonucleotides obtained from the ribonucleoside reductase complex
regulation site & substrate specificity site
ATP activates enzyme activity in the regulation site (R1) and ( ) inhibits it
dATP
what subunit is the regulation site on
R1
where can dCTP be used
DNA synthesis or deamination to produce dUTP
dUTP can be converted to what
dUMP
what is the only substrate for thymidylate synthase
dUMP
T or F: uracil & thymine structure only differ by a methyl group
T
what reaction does thymidylate synthase catalyze?
methylation
dihydrofolate reductase
methyelne-tetrahydrofolate reduces to tetrahydrfolate using NADPH
what is dTMP converted to
dTTP- substrate for DNA synthesis
acyclovir
treats herpes simplex- haults DNA synthesis bc no ribose ring on it to continue synthesis
anti-viral therapies
reverse transcriptase, stops DNA synthesis
what is the target for anti-cancer drugs
thymidylate synthase
5-fluorouracil
similar structure to UMP, inactivates thymidylate synthase to stop DNA production
3 compounds that are analogues of dihydrofolate & inhibit it for anti-cancer drugs
methotrexate, aminopterin & trimethoprim
which molecule does not regulate de novo synthesis of purines
UMP
what is the major end product of purine degradation
uric acid
