Formation of deoxyribonucleotides and nucleotide degradation Flashcards
what is the enzyme that can turn ribonucleotides into deoxyribonucleotides?
ribonucleotide reductase
what substance is produced by purine degradation?
uric acid
what substance is produced by pyrimidine degradation?
malonyl-coA
which enzyme transfers a methyl group from deoxyUracilMonoPhosphate to form Thymine
thymidylate synthase
what is R1 of the ribonucleotide reductase enzyme?
this and another R1 form a homodimer, and they are the regulatory site of the enzyme. They contain specificity/hexamerization (ATP)/activity site(ATP/dATP) that are called allosteric sites
what is the R2 of the ribonucleotide reductase enzyme?
it is the reactive component, it contains Fe3+ ions that are used to form a thenolate radical (Tyr residue) that is used to form a side chain that is present as a cysteine side chain.
how does DNA differ from RNA
1- its nucleotides have 2’-deoxyribose residues
2- it uses the base thymine instead of uracil
when the R2 subunit has formed the thiol radical groups, what happens next?
the enzymes’ oxidized thioester bonds must be reduced once more. This is done by thioredoxin reductase.
explain thioredoxin reductase?
it has cysteine residues, and redox active thiol groups, and a FAD prosthetic group.
what is the terminal reducing agent in the thioredxon reaction?
NADPH
what is the end product of ribonuleotide reductase
dNDP - Deoxy-nucleotide-di-phosphate
to form dNTP, which enzyme is used?
the nucleoside diphosphate kinase
how does dUMP form dTTP?
dUTP is turned into dUMP by dUTP diphosphohydrolase.
dUMP is then methylated by thymidylate synthase to form dTMP
dTMP is phosphorylated to form dTTP
thymidylate synthase is inhibited by?
5-fluorodeoxyuridylate FdUMP, this is a mechanism based inhibitor or a suicide substrate. it is a useful therapeutic drug
inhibition of DHFR (dihydrofolate reductase) is done in which therapy?
cancer therapy. These can be aminopterin, methotrexate, trimethoprim
how is THF produced from DHF?
By DHF reductase
how are dietary nucleic acids absorbed?
they are broken down into their nucleotides in the intestine by pancreatic nucleases and intestinal phosphodiesterase. Note that they can survive the acidic stomach!
what happens to ionic nucleotides that cannot pass the membrane?
they are hydrolysed to their nucleosides, by nucleotidases and non specific phosphatases
nucleosides can be further degraded into ?
free bases and ribose or ribose-1-phosphate, by nuclosidase and nucleoside phosphorylase
what is the function of a nucleosidase?
to remove the phosphate moiety from a nucleotide to make it into a nucleoside
what is the final action in the purine degradation pathway?
xanthine is converted by xanthine oxidase to uric acid
adenosine deaminase is an alpha/beta enzyme with a zinc ion in its active site (at the C terminal), what happens if the active site is damaged?
these mutations specifically kill lymphocytes and severe combined immunodeficiency disease SCID. In these conditions dATP levels increase thus ribonuceotide reductase is inhibited thus DNA synthesis is stopped
how does muscle benefit form the purine cycle?
it replenishes it citric acid cycle intermediates with fumarate from the purine cycle
gout
HGPRT gene mutation, severe levels of uric acid, can be treated by administering allopurinol with inhibits xanthine oxidase
read slide 30
for pyrimidine pathway
xanthine oxidase rxn produces?
h202 as a by product
thymidylate synthase is inhibited in cancer therapy by?
5- fluorodeoxyuridylate FdUMP (a suicide substrate)
Lymphoid tissue is particularly active in ?
deoxyadenosine phosphorylation
