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29 Cards in this Set

  • Front
  • Back
what does a nucleotide consist of?
A nitrogenous base, a pentose monosaccharide, and 1, 2 or 3 phosphate groups.
What does a nucleoside consist of?
a nitrogenous base and a pentose sugar, no phosphate
At which steps is puring biosynthesis regulated?
At the first two steps and at the branch point.
From where is ribose-5-phosphate largely derived?
From glucose-6-phosphate via the pentose phosphate synthetic pathway.
What is the first step in de novo biosynthesis of purines?
The first step involves the formation of 5-phosphoribosyl-1-pyrophosphate (PRPP).
What is the second step in de nove biosynthesis of purines?
Synthesis of 5'-phosphoribosylamine
What is the commited and rate-limiting step in purine synthesis?
Formation of 5'-phosphoribosylamine.
Describe how AMP is formed from IMP. Name the intermediate.
IMP to adenylosuccinate to AMP.
Describe how GMP is formed from IMP. name the intermediate.
IMP to XMP (xanthosine monophosphate) to GMP.
How are nucleoside monophosphates coverted to nucleoside diphosphates?
via base-specific nucleoside monophosphate kinases.
How are nucleoside diphosphates converted to nucleoside triphosphates?
Via nucleoside diphosphate kinases (general for all nucleosides).
What enzyme/protein is used in converted ribonucleosides to deoxyribonucleosides?
Ribonucleotide reductase.
What substrates are used in the formation of deoxyribonucleotides?
The substrates are nucleoside diphosphates.

A/C/G/UDP to dA/dC/dG/dUDP
Name the two enzymes involved in purine salvage and tell which purines are converted.
HPRT (hypoxanthine-guanine phosphoribosyl transferase) converted hypoxanthine to IMP; guanine to GMP

This is defective in Lesch-Nyhan syndrome

APRT (adenine phosphoribosyl transferase) converts adenine to AMP
List the steps in purine degradation.
1. Adenine is deaminated: AMP to IMP; adenosine to inosine

2. dephosphorylation: IMP to inosine; GMP to guanosine

3. removal of sugars: inosine to hypoxanthine; guanosine to guanine

4. deamination of guanine: guanine to xanthine

5. xanthine oxidase converts hypoxanthine to xanthine and xanthine to uric acid
What are sulfonamides?
antibiotics that inhibit bacterial production of folic acid; humans do not produce folic acid and are thus not affected
What are the uses and mechanisms of methotrexate?
inhibits mammalian dihydrofolate, thus depleting the N10 formyl-tetrahydrofolate required for carbon donation to purine positions 2 and 8; limiting purine synthesis inhibits DNA replication and cell proliferation in rapidly growing cancer cells; significant toxicity issues for other rapidly proliferating tissues
what is the use and mechanisms of trimethoprim?
inhibits biosynthesis in prokaryotes by selectively inhibiting bacterial dihydrofolate reductase
What is the use and mechanism of mycophenolic acid?
reversible, uncompetitive inhibitor of IMP dehydrogenase; prevents GMP synthesis thus depriving rapidly proliferating B and T cells of guanosine nucleotides for nucleic acid synthesis; used as an immunosuppresive to prevent graft rejection.
What is gout a result of?
A build up of uric acid, either overproudction (rare) or underexcretion.

Deposit of sodium urate crystals induces an inflammatory response involvig granulocyte re cruitement.

Overproduction can be treated with allopurinol.
How can overproduction of uric acid be treated?
How do mammamls regulate the synthesis of pyrimidines?
via the first step in the pathway involving CPS II.
how do prokaryotes regulate the synthesis of pyrimidines?
Via the second step (aspartate transcarbamoylase))
Outline the steps in pyrimidine synthesis.
glutamine to carbamoyl phosphate to carbamoyl aspartate to dihydrooroate to oroate to OMP (oritidine 5'-monophostphate) to UMP (uridine 5'-monophosphate)
what is the precursor of all pyrimidines?
How is CTP formed?
CTP is generated by aminating C4 of UTP via glutamine (CTP synthetase)
How is dTMP formed?
dTMP is formed by methylaing C5 of dUMP via N5, n10 methylene-tetrahydrofolate. (thymidylate synthase)
How are pyrimidines degraded?
The pyrmidine ring is broken during degradation and the end products of pyrmidine degradation are highly soluble.
What is 5-fluorouracil?
It is a potent antitumor agent that is metabolically converted to 5-fluoro-dUMP which inhibits thymidylate synthase via irreversible binding (suicide inhibitor). This prevents formation of DTMP, thus limiting DNA synthesis in rapidly dividing cells.