Nucleotides Flashcards
Contains D ribose or 2 deoxy D ribose
Linked ro N1 of a pyrimidine
Or N-9 of purine
By B-N-glycosidic bond
Nucleoside
In nucleotides, the phosphoryl group is usually attached to C-5 of the
Pentose
Polynucleotides are written in what direction
5’ to 3’
Rate limitjng enzyme of purine synthesis
PRPP glutamyl amidotransferase
Rate limiting enzyme of pyrimidine synthesis
Carbamoyl phosohate II
Donors of atoms in purine synthesis
GAC GN
Glutamine
Aspartate
Carbon dioxide
Glycine
N10-formyltetrahydrofolate
Donors of atoms in pyrimidine synthesis
GAC
Glutamine
Aspartate
Carbon dioxide
Sequence of steps in purine synthesis
Ribose 5P —-> purine ring construction
Sequence of steps in pyrimidine synthesis
Pyrimidine ring formation —-> attachment to ribose 5phosphate
Parent molecule purine synthesis
Inosine monophosphate
Parent molecule pyrimidine synthesis
Orotidine monophosphate
Products of of purine synthesis (2)
GMP (requires ATP)
AMP (requires GTP)
Products of PYR synthesis (2)
CTP, TMP, UDP
UMP—> UTP —> CTP
UMP —-ribonucleotide reductase —> dUMP
dUMP—-thymidylate synthase—> TMP
Enzyme that activates r5p
PRPP syntetase
R5P—>5-PRPP
Energy requirement for prpp reaction
ATP to AMP
Donor of R5P of nucleotides, whether synthesized de novo or through salvage pathways
PRPP
Inhibits PRPP synthetase
ADP
Inhibits PRPP —-> 5 phosphoribosylamine
Enzyme glutamine PRPP amidotransferase
AMP IMP
GMP
Pyrimidine synthesis
Multisubunit enzyme that reduces nucleoside diphosohates to their deoxy forms
Ribinucleotide reductase
Ribinucleotide reductase facilitate redox reactions that require ____ and ____
Thioredoxin
NADPH
Pyr synthesis
Enzyme that converts dUMP to thymine
Thymidilate synthase
Cofactor for thymidilate synthase in pyr synthesis
N5, N10 methylene tetrahydrofolate
Inhibited by 5-fluorouracil
Purine/pyrimidine
Ring cannot be cleaved in human cells
Purine
Purine/pyrimidine
Ring can be opened and degraded ro water soluble products
Pyr
Product of purine degradatiom
Uric acid
Product of pyr degradation (2)
Beta alanine (precursor for acetyl CoA)
Beta aminoisobutyrate (precursor for succinyl CoA)
Disease associated with accumulation of purine, pyrimidine
Gout
Orotic aciduria, respectively
Conversion of purines, ribonucleotides, and their deoxyribonucleotides to mononucleotides
Salvage purine pathway
Requires LESSenergy than de novo synthesis
Salvage pathway
2 irreversible enzymes in salvage pathway of purine
APRT and HGPRT
Adenine phosphoribosyltransferase
Hypoxanthine guanine phosphoribosyltransferase
Source of ribose 5 phosphate in purine salvage pathway
PRPP
Drugs that inhibit nucleotide metabolism
Inhibits xanthine oxidase
Allopurinol
Drugs that inhibit nucleotide metabolism
Structural analog of PABA
Competitively inhibits dihydripteroate synthase
(Conversion of PABA to folate)
Sulfonamides
Drugs that inhibit nucleotide metabolism
Stuctural analog of folate
Slectively inhibits bacterial dihydrofolate reductase
(Conversion of THF from folate)
Trimethoprim
Drugs that inhibit nucleotide metabolism
Metbolically converted to 5 FdUMP which inhibits thymidilate synthase
(DTMP to dUMP)
5 FU
Inhibits dihydrofolate reductase which reduces the tetrahydrofolate supply for the synthesis of thymine
Methotrexate
Drugs that inhibit nucleotide metabolism
Reversible inhibitor of IMP dehydrogenase
Depriving T and B lymphocytes of nucleic acids
(Fglu rxns)
Mycophenolate
Enzyme deficiency
Lesch nyhan
HGPRT (inc PRPP and uric acid)
Enzyme deficiency
SCID
Adenosince deaminase
Inc dATP inhibits ribonucleotide synthase
Enzyme deficiency
Von Gierke
Glucose 6 phosphatase
Inc ribose 5 phosphate
Enzyme deficiency
Orotic aciduria
Orotidine phosphate decarboxylase or
Orotate phosphoribosyl transferase
Enzyme deficiency
Beta hydroxybutyric aciduria
Dihydropyridine dehydrigenase
X linked
Gout, self-mutilation, mental retardation
Lesch nyhan
Lymphocytipenia
Death before age because of overwhelming infection
Treat with BM transplant
Gene therapy
SCID
Purine overproduction and hyperuricemia
Von Gierke
Poor growth
Megaloblastic anemia
Orotate in urine
Treat with uridine
Orotic aciduria
Combined uraciluria-thyminuria
Impaired formation of beta alanine and of bet aminoisobutyrate
Beta hydroxybutyric aciduria