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Definition
consists of a nitrogenous base
a pentose monosaccharide
and a number of phosphate groups
nitrogenous base is linked by a beta-glycosidic bond from the 1'-position |
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consits of the nitrogenous base and pentose sugar
NO PHOSPHATE GROUP |
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numbered from 1 to 9
beta glycosidic bond at N9
os- added to indicate sugar (adenosine) |
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numbered from 1 to 6
linked to pentose sugars via N1
d added to indicate sugar (cytidine) |
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Definition
activated precursors of DNA and RNA
derivatieces are activated intermediates in biosynthesises
ATP is currency of energy, GTP hydrolysis is essential for macromolecualr translocation events
Adenosine nucleotides are components of major coenzymes
participate in regulatory signaling systems |
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| Purine/ pyrimidine deficiency states |
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Definition
rare in humans
occasionally occurs during pregnancy, owing to increased folate requirements
condition is manifested as megaloblastic anemia
can also arise from vitamin B12 deficiency due to poor utilization of N5-methyl tetrahydrofolate |
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| 1st step in Purine Biosynthesis |
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Definition
Ribose 5- phosphate derived from ppp is converted to PRPP by PRPP synthetase
inhibitor of this step are purine ribonucleotides, activator free phosphate |
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| 2nd step in Purine Biosynthesis |
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Definition
Rate-limiting and committed step of purine biosynthesis
synthesis of 5' phosphoribosylamine
glutamine donates an amide group which replaes pyrophosphate on the 1 carbon configuration of C-1 is alpha
inhibitors are amp, gmp, imp activator : prpp |
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| 3rd step in Purine Biosynthesis |
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Definition
| several steps convert 5'-phosphoribosylamine into inosine 5'-monophosphate, the progenitor of all purine nucleotides |
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Definition
Aspartate - N1
N10-formyl-tetrahydrofolate - C2, C8
Glutamine N9, N3
Glycine N7, C5, C4
CO2 C6 |
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Definition
PABA analogs
inhibit bacteial production of folic acid
humans do not produce foic acid de novo, thus unaffected
antibacterial, need folic acid to make purines |
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Folate analog
inhibits mammalian dihydrofolate reductase this depletes the N10-formyl-tetrahydrofolate required for purine synthesis
inhibits DNA replication and cell prolif in cancer cells
significant toxicity to cells rapidly growing ie hair, WBC, epithelium
depletion of tetrahydrofolate inhibits dTMP production by limiting the supply of N, N10 methylene-tetrahydrofolae |
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Folate analog
inhibits purine biosynthesis in prokaryotes by selectively inhibiting bacterial dihydrofolate reductase
used frequently for urinary tract infection |
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Definition
IMP is transformed to adenylosuccinate then to AMP
first step inhibited by AMP
GTP is utilized as an energy source |
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Definition
IMP is converted to xanthosine nonophosphate (XMP) then to GMP
first step inhibited by GMP
ATP utilized as an energy source
can inhibit their own specific synthesis but leave the other alone
balance kept by cross talk |
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Definition
drug is a reversible uncompetitive inhibitor of inosine monophosphate dehydrogenase
the drug deprives rapidly proliferating T and B cells of key components of nucleic acids
prevent graft rejection by inhibiting GMP synthesis
t and b cells do not use recycling of nucleotdies and only use de nove and are more suseptible than other cells |
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Definition
convert nucleoside monophosphates to diphosphate forms
donor ATP, no distinguish from ribos v deoxy |
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Definition
converts nucleoside diphosphate to triphosphate
donor ATP, no distinguish from ribos v deoxy |
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Term
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Definition
conversion of ribonucleotides to deoxyribonucelotides
4 enzyme subunits (2 b1, 2 b2)
specific nucleotides bind to b1 subunit, diphosphate substrates enter between the b1 and b2 subunits
involves formation of a disulfide bond |
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Definition
| regenerates the ribonucleotide reductase by reduction of the formed disulfide bond |
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Definition
purines recovered from cellular nucleic acid turnover or dietary intake
couples free purines to PRPP using one of two enzymes with loss of pyrophosphate |
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| Hypoxanthine-guanine phosphoribosyltransferase (HPRT) |
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Definition
purine salvage
converts Hypoxanthine + PRPP to IMP
Guanine + PRPP to GMP |
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| Adenine phosphoribosyltransferase (APRT) |
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Definition
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X-linked
deficiency in HPRT
decreased IMP and GMP concentrations activate endogenous purine synthesis at the committed step
increased purine synthesis results in overproduction of uric acid
leads to gout, urate kidney stones, neurological disorders (involountary self-mutatalation)
die by 20 of massive kidney failure |
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| Degradation of dietary nucleic acids |
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Definition
occurs in the small intestine
very little is actually used for tissue nucleic acids
generally degraded to uric acid in the intestinal mucosa |
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Term
| Steps for degradation of cellular purine nucleotides |
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Definition
1. adenine is deaminated (AMP or adenosine)
2. IMP and GMP are converted into nucleoside forms by 5'nucleotidase
3. The sugar moieties are removed yielding guanine adn hypoxnthine
4. deamination of guanine gives xanthine
5. xanthine oxidase converts hypoxanthine to xanthine
6. subsequent oxidation of xanthine genreates uric acid, which is excreted in the urine |
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Term
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Definition
caused by overproduction or underexcretion of uric acid
leads to deposition of sodium urate in tissues especially in kidney and joints
induces an inflammatory response involving granulocyte recruitment |
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Definition
treatment of gout resulting from overproduction of uric acid
metabolized to form an inhibitor of xanthine oxidase which results in accumulation of hyoxanthine and xanthine which is more soluble than uric acid |
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| Adenosine Deaminase deficiency (ADA) |
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Definition
autosomal recessive loss of adenosine deaminase
this prevents deamination of adenosine to inosine resulting in accumulation of adenosine and releate nucleotides
increased dATP inhibits ribonucleotide reductase, thus depleting cellular pools of dNTPs for DNA synthesis
inhibition of DNA synthesis prevents proliferation of B and T cells and is manifested as severe combined immunodeficiency disease |
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Term
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Definition
not assembled on a PRPP scaffold
construted from basic components to form the 6-mem orotate ring which is then transferred to PRPP |
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| Mammalian pyrimidine synthesis |
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Definition
regulateed at the first step, catalyzed by carbamoyl phosphate synthetase II
inhibited by UTP
activated by ATP and PRPP |
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| Prokaryotes pyrimidine synthesis |
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Definition
sythesis of pyrimidines is regulated at the second step by aspartate transcarbamoylase
inhibited by CTP
all pyrimideine nucleotides are derived from a UMP precursor |
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| Contributors to pyrimidine ringe |
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Definition
Aspartic Acid C4, C5, C6, N1
Glutamine N3
CO2 C2 |
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Definition
2 reactions required for synthesis of UMP are catalyzed by a common protein, involving different protein domains
genetic UMP synthase deficiency prevents UMP formation results in growth abnormalities, megaloblastic anemia, urinary excretion of orotate
diet rich in uridine improves the anemia and decreases orotate excretion |
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ctp is generated by amination of UTP at C4 by CTP synthetase
glutamine serves as the amino donor |
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Definition
generated by methylation of dUMP at C by thymidylate snythase
N5, N10- methylene-tetrahydrofolate is the methyl donor |
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Definition
an antitumor agent that is converted to 5-fluro dUMP which inhibits thymidylate synthetase via irreversible binding
prevents formation of dTMP, thus limiting DNA synthesis in rapidly dividing cells |
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