Chapter 18: Nucleotide Metabolism Flashcards
what does a nucleotide consist of?
- nitrogenous base
- phosphate group
- deoxyribose sugar
where are the covalent bonds located in a nucleotide?
- between the phosphate group and sugar
- between the ring nitrogen of the base and a ring carbon of the sugar
which groups are responsible for linking each nucleotide together in a chain of DNA?
phosphate groups
how do the phosphate groups form bonds to link DNA?
a phosphate group of one nucleotide reacts with an -OH group present on the deoxyribose ring of another nucleotide, forming and eliminating a H20 molecule
where do the atoms that form the purine ring come from?
- aspartate
- CO2
- glycine
- glutamate
- 10-formyltetrahydrofolate
is the purine ring structure synthesized as a free base or as a substituent of ribose-5-phosphate?
as a substituent of ribose-5-phosphate
where does the ribose 5-phosphate for purine biosynthesis come from?
PRPP
what is the initial product of the purine nucleotide biosynthetic pathway?
inosine 5’-monophosphate (IMP)
describe the synthesis of IMP
- 10 step process
- nucleotide biosynthesis is energetically expensive-ATP is consumed to make PRPP and in steps 2, 4, 5, 6, and 7 (plus in making glutamine from glutamate and ammonia)
what can IMP be converted to?
AMP or GMP
how is purine nucleotide biosynthesis regulated?
**negative feedback inhibition
what is the first committed step of purine nucleotide biosynthesis?
**the conversion of PRPP to 5-phosphoribosylamine — major point of regulation
what enzyme converts PRPP to 5-phosphoribosylamine?
glutamine-PRPP amidotransferase
what is PRPP to 5-phosphoribosylamine inhibited by?
IMP, AMP, and GMP
where do the atoms for the pyrimidine ring structure come from?
- aspartate
- glutamine
- bicarbonate
what is a common precursor for some pyrimidine nucleotides?
uridine 5’-monophosphate
does purine or pyrimidine synthesis require more ATP?
purine synthesis
what is the general process of pyrimidine synthesis?
*build 6 membered ring and then attach it to ribose
opposite of purine
which steps of pyrimidine synthesis occur through a multi-enzyme complex in eukaryotes?
steps 1-3 and 5 & 6
catalyzes the conversion of orotidine 5-monophosphate (OMP) –> uridine 5’-monophosphate (UMP)
OMP decarboxylase
which molecule is an ATCase transition state analog?
- **N-phosphonacetyl-L-aspartate (PALA)
- acts as an inhibitor
what is the process of CTP synthesis?
UMP —->UDP—>UTP—>CTP
- all steps require hydrolysis of ATP
- UTP—>CTP requires input of glutamine (donates nitrogen) and output of glutamate
how is pyrimidine biosythesis regulated?
**allosteric regulation - both positive and negative effectors
what are the effectors of pyrimidine biosynthesis?
- ATP activates ATCase
- UTP inhibits ATCase
- CTP inihibits CTP synthetase and ATCase
- GTP activates CTP synthetase
what is the significance of ATCase?
- catalyzes the first committed step in pyrimidine biosynthesis
- Aspartate + cabamoyl phosphate –> carbamoyl aspartate
- major point of regulation
how does the reduction of ribonucleotides to deoxyribonucldeotides occur?
- reduction occurs at the nucleoside diphosphate level
- NADPH provides the reducing power
- electrons are transferred from NADPH to ribonucleotide reductase
how is ribonucleotide reductase regulated?
complicated mechanism because each monomer has 3 binding sites
what are the binding sites of ribonucleotide reductase and what do they signify?
- ligand bound to activity site –> determines how much catalysis occurs
- ligand bound to specificity site –> dictates what can bind to active site
- catalytic site –> activity of active site
when is ribonucleotide reductase inactive?
- dATP bound to activity site
- nothing bound to specificity site
when is the ribonucleotide reductase active site specific for CDP or UDP?
- ATP bound to activity site
- ATP or dATP bound to specificity site
when is the ribonucleotide reductase active site specific for GDP?
- ATP bound to activity site
- dTTP bound to specificity site
when is the ribonucleotide reductase active site specific for ADP?
- ATP bound to activity site
- dGTP bound to specificity site
how is dUMP converted to dTMP?
- methylation
- UMP –> UDP –> dUDP –> dUMP –> dTMP
what is the process of nucleic acid degradation?
- Nucleic acids –> mononucleotides
- nucleases - Mononucleotides –> nucleosides
- nucleotidases
- phosphatases - nucleosides –> bases
- nucleosidases
- nucleoside phosphorylases - Bases –> 5’ - mononucleotides OR degradation products
are most purines and pyrmidines salvaged or degraded?
- most are salvaged (save energy) and form 5’-mononucleotides
- some are catabolized to degradation products
how are purine nucleotides degraded?
degraded to their respective purines through reaction with PRPP
how are pyrimidines salvaged?
orotate phosphoribosyltransferase - catalyzes step 5 of biosynthesis pathway
how are purines salvaged?
- interconverted
* -oxy versions can interconvert, de-oxy versions CANNOT
how does purine catabolism occur?
- hypoxanthine and guanine are broken down to uric acid
- uric acid is catabolized through oxidation and hydrolysis
how are pyrimidines salvaged?
interconverted
how does pyrimidine catabolism occur?
uracil and thymine are catabolized to acetyl CoA and succinyl CoA, which can enter the krebs cycle
what are the purines?
- adenine
- guanine
do purines have one or two rings?
two
do pyrimidines have one or two rings?
one
