Chapter 18: Nucleotide Metabolism Flashcards

(44 cards)

1
Q

what does a nucleotide consist of?

A
  • nitrogenous base
  • phosphate group
  • deoxyribose sugar
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2
Q

where are the covalent bonds located in a nucleotide?

A
  • between the phosphate group and sugar

- between the ring nitrogen of the base and a ring carbon of the sugar

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3
Q

which groups are responsible for linking each nucleotide together in a chain of DNA?

A

phosphate groups

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4
Q

how do the phosphate groups form bonds to link DNA?

A

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

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5
Q

where do the atoms that form the purine ring come from?

A
  • aspartate
  • CO2
  • glycine
  • glutamate
  • 10-formyltetrahydrofolate
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6
Q

is the purine ring structure synthesized as a free base or as a substituent of ribose-5-phosphate?

A

as a substituent of ribose-5-phosphate

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7
Q

where does the ribose 5-phosphate for purine biosynthesis come from?

A

PRPP

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8
Q

what is the initial product of the purine nucleotide biosynthetic pathway?

A

inosine 5’-monophosphate (IMP)

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9
Q

describe the synthesis of IMP

A
  • 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)
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10
Q

what can IMP be converted to?

A

AMP or GMP

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11
Q

how is purine nucleotide biosynthesis regulated?

A

**negative feedback inhibition

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12
Q

what is the first committed step of purine nucleotide biosynthesis?

A

**the conversion of PRPP to 5-phosphoribosylamine — major point of regulation

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13
Q

what enzyme converts PRPP to 5-phosphoribosylamine?

A

glutamine-PRPP amidotransferase

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14
Q

what is PRPP to 5-phosphoribosylamine inhibited by?

A

IMP, AMP, and GMP

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15
Q

where do the atoms for the pyrimidine ring structure come from?

A
  • aspartate
  • glutamine
  • bicarbonate
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16
Q

what is a common precursor for some pyrimidine nucleotides?

A

uridine 5’-monophosphate

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17
Q

does purine or pyrimidine synthesis require more ATP?

A

purine synthesis

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18
Q

what is the general process of pyrimidine synthesis?

A

*build 6 membered ring and then attach it to ribose

opposite of purine

19
Q

which steps of pyrimidine synthesis occur through a multi-enzyme complex in eukaryotes?

A

steps 1-3 and 5 & 6

20
Q

catalyzes the conversion of orotidine 5-monophosphate (OMP) –> uridine 5’-monophosphate (UMP)

A

OMP decarboxylase

21
Q

which molecule is an ATCase transition state analog?

A
  • **N-phosphonacetyl-L-aspartate (PALA)

- acts as an inhibitor

22
Q

what is the process of CTP synthesis?

A

UMP —->UDP—>UTP—>CTP

  • all steps require hydrolysis of ATP
  • UTP—>CTP requires input of glutamine (donates nitrogen) and output of glutamate
23
Q

how is pyrimidine biosythesis regulated?

A

**allosteric regulation - both positive and negative effectors

24
Q

what are the effectors of pyrimidine biosynthesis?

A
  • ATP activates ATCase
  • UTP inhibits ATCase
  • CTP inihibits CTP synthetase and ATCase
  • GTP activates CTP synthetase
25
what is the significance of ATCase?
* catalyzes the first committed step in pyrimidine biosynthesis * Aspartate + cabamoyl phosphate --> carbamoyl aspartate * major point of regulation
26
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
27
how is ribonucleotide reductase regulated?
complicated mechanism because each monomer has 3 binding sites
28
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
29
when is ribonucleotide reductase inactive?
- dATP bound to activity site | - nothing bound to specificity site
30
when is the ribonucleotide reductase active site specific for CDP or UDP?
- ATP bound to activity site | - ATP or dATP bound to specificity site
31
when is the ribonucleotide reductase active site specific for GDP?
- ATP bound to activity site | - dTTP bound to specificity site
32
when is the ribonucleotide reductase active site specific for ADP?
- ATP bound to activity site | - dGTP bound to specificity site
33
how is dUMP converted to dTMP?
- methylation | - UMP --> UDP --> dUDP --> dUMP --> dTMP
34
what is the process of nucleic acid degradation?
1. Nucleic acids --> mononucleotides - nucleases 2. Mononucleotides --> nucleosides - nucleotidases - phosphatases 3. nucleosides --> bases - nucleosidases - nucleoside phosphorylases 4. Bases --> 5' - mononucleotides OR degradation products
35
are most purines and pyrmidines salvaged or degraded?
- most are salvaged (save energy) and form 5'-mononucleotides - some are catabolized to degradation products
36
how are purine nucleotides degraded?
degraded to their respective purines through reaction with PRPP
37
how are pyrimidines salvaged?
orotate phosphoribosyltransferase - catalyzes step 5 of biosynthesis pathway
38
how are purines salvaged?
* interconverted | * -oxy versions can interconvert, de-oxy versions CANNOT
39
how does purine catabolism occur?
- hypoxanthine and guanine are broken down to uric acid | - uric acid is catabolized through oxidation and hydrolysis
40
how are pyrimidines salvaged?
interconverted
41
how does pyrimidine catabolism occur?
uracil and thymine are catabolized to acetyl CoA and succinyl CoA, which can enter the krebs cycle
42
what are the purines?
- adenine | - guanine
43
do purines have one or two rings?
two
44
do pyrimidines have one or two rings?
one