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Biochemistry > Chapter 18: Nucleotide Metabolism > Flashcards

Chapter 18: Nucleotide Metabolism Flashcards

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
Q

what is the significance of ATCase?

A
  • catalyzes the first committed step in pyrimidine biosynthesis
  • Aspartate + cabamoyl phosphate –> carbamoyl aspartate
  • major point of regulation
26
Q

how does the reduction of ribonucleotides to deoxyribonucldeotides occur?

A
  • reduction occurs at the nucleoside diphosphate level
  • NADPH provides the reducing power
  • electrons are transferred from NADPH to ribonucleotide reductase
27
Q

how is ribonucleotide reductase regulated?

A

complicated mechanism because each monomer has 3 binding sites

28
Q

what are the binding sites of ribonucleotide reductase and what do they signify?

A
  • 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
Q

when is ribonucleotide reductase inactive?

A
  • dATP bound to activity site

- nothing bound to specificity site

30
Q

when is the ribonucleotide reductase active site specific for CDP or UDP?

A
  • ATP bound to activity site

- ATP or dATP bound to specificity site

31
Q

when is the ribonucleotide reductase active site specific for GDP?

A
  • ATP bound to activity site

- dTTP bound to specificity site

32
Q

when is the ribonucleotide reductase active site specific for ADP?

A
  • ATP bound to activity site

- dGTP bound to specificity site

33
Q

how is dUMP converted to dTMP?

A
  • methylation

- UMP –> UDP –> dUDP –> dUMP –> dTMP

34
Q

what is the process of nucleic acid degradation?

A
  1. Nucleic acids –> mononucleotides
    - nucleases
  2. Mononucleotides –> nucleosides
    - nucleotidases
    - phosphatases
  3. nucleosides –> bases
    - nucleosidases
    - nucleoside phosphorylases
  4. Bases –> 5’ - mononucleotides OR degradation products
35
Q

are most purines and pyrmidines salvaged or degraded?

A
  • most are salvaged (save energy) and form 5’-mononucleotides
  • some are catabolized to degradation products
36
Q

how are purine nucleotides degraded?

A

degraded to their respective purines through reaction with PRPP

37
Q

how are pyrimidines salvaged?

A

orotate phosphoribosyltransferase - catalyzes step 5 of biosynthesis pathway

38
Q

how are purines salvaged?

A
  • interconverted

* -oxy versions can interconvert, de-oxy versions CANNOT

39
Q

how does purine catabolism occur?

A
  • hypoxanthine and guanine are broken down to uric acid

- uric acid is catabolized through oxidation and hydrolysis

40
Q

how are pyrimidines salvaged?

A

interconverted

41
Q

how does pyrimidine catabolism occur?

A

uracil and thymine are catabolized to acetyl CoA and succinyl CoA, which can enter the krebs cycle

42
Q

what are the purines?

A
  • adenine

- guanine

43
Q

do purines have one or two rings?

A

two

44
Q

do pyrimidines have one or two rings?

A

one

Biochemistry (9 decks)

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