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Biochemistry > BB451 exam 2 - Nucleotide Metabolism > Flashcards

BB451 exam 2 - Nucleotide Metabolism Flashcards

1
Q

nucleoside

A

sugar + nitrogenous base

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2
Q

nucleotide

A

sugar + nitrogenous base + phosphate

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3
Q

purines

A

adenine, guanine

double ring

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4
Q

pyrimidine

A

thymine, cytosine, uracil

single ring

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5
Q

adenine pairs with..

A

thymine (DNA)

uracil (RNA)

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6
Q

guanine pairs with…

A

cytosine

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7
Q

deamination of cytosine

A

–> uracil

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8
Q

2 general pathways of synthesis

A

de novo - from scratch

salvage - use breakdown products of others

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9
Q

___ synthesized first

A

ribonucleotides

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10
Q

deoxyribonucleotides made from…

A

ribonucleoside diphosphates

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11
Q

de novo synthesis precursors for pyrimidine synthesis

A

amino acids, carbamoyl phosphate, sugars

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12
Q

pyrimidine ring + PRPP –>

A

UTP

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13
Q

pyrimidine synthesis: base if made…

A

base made apart from sugar and later attached to it

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14
Q

carbamoyl phosphate synthetase

A

enzyme that uses tunneling/channeling of substrates though it to protect intermediates from water
bicarbonate + NH3 + 2 ATP –> carbomyl phosphate + aspartate –> ring

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15
Q

most important regulatory enzyme in pyrimidine synthesis

A

ATCase
balance amounts of purines and pyrimidines
measures amount of energy available via amount of ATP present

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16
Q

ATCase catalyzes

A

aspartate + carbomoyl phosphate –> pyrimidine ring

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17
Q

ATCase allosterically activated by

A

ATP and inactivated by CTP (end product)

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18
Q

RPRR

A

source of NADPH and ribose

ribose -5 phosphate via pentose phosphate pathway

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19
Q

first pyrimidine nucleotide made

A

UMP

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20
Q

UMP is …

A 
phosphorylated to UDP by uridine monophosphate kinase (UMP kinase) 
uses ATP (can run backwards to get ATP)
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21
Q

UDP converted to UTP by..

A

NADPK (for all diphosphates)

can go back and forth to balance triphosphates

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22
Q

UTP to…

A

CTP via CTP synthase by amination

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23
Q

CTP synthase

A

last regulated enzyme
UTP –> CTP
inhibited by CTP (balance between CTP and UTP)
*completed synthesis of ribo-pyrimidines (UTP and CTP)

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24
Q

purine synthesis: base is assembled…

A

on the sugar (PRPP ring)

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25
Q

purine synthesis uses atoms from….

A

aspartate, glycine, glutamine, CO2, tetrahydrofolate derivate (single C donor)

26
Q

most important regulatory enzyme in purine synthesis

A

PRPP amidotransferase
controls purine production - slows when one nucleotide is too high in concentration
balance between AMP and GMP

27
Q

PRPP amidotransferase inhibited by

A

fully by AMP and GMP (end products)

partly when only one is present

28
Q

purine synthesis begins with

A

PRPP - ribose ring

29
Q

single carbon donor in purine synthesis

A

folate

30
Q

shortage of folate in pregnancy..

A

–> neural tube defects (70% reduction by supplementation)

31
Q

first purine like intermediate

A

IMP (I in some transfer RNAs)
branch on synthesis of GMP and AMP
purine link base hypoxanthine linked to ribose

32
Q

process of making IMP

A

fumarate released (connecting to CAS)

33
Q

IMP oxidation –>

A

GMP

inhibited by GMP, energy from ATP

34
Q

IMP –> AMP

A

aspartic acid donates amine
fumarate released
inhibited by AMP, energy from GTP

35
Q

balance between AMP and GTP

A
  • PRPP amidotransferase
  • GMP production inhibited by GMP, energy from ATP
  • AMP production inhibited by AMP, energy from GTP
36
Q

AMP and GMP –> ADP and GDP by

A

AMP kinase and GMP kinase

37
Q

ADP and GDP –> ATP and GTP by

A

NDPK

38
Q

deoxyribonucleotides made starting with..

A

RNR (ribonucleotide reductase)
catalyzes ribonucleoside diposphates –> deoxyribonucleoside diphosphates
ex: ADP —> dADP

39
Q

RNR works on…

A

all ribonucleoside diphosphates

40
Q

dADP –> dATP via

A

NDPK (all nucleoside diphosphates)

41
Q

making thymine nucleotides (first 2 steps)

A

UDP–> dUDP via RNR

dUDP –> dUTP via NDPK

42
Q

making thymine nucleotides…dUTP –> dUMP by

A

dUTPase

43
Q

making thymine nucleotides dUMP –> dTMP by

A

thymidylate synthase - requires folate to put methyl group onto U to make T

44
Q

dTMP–>

A

dTDP –> dTTP via NDPK

45
Q

why T in DNA not U

A

u will form stable base pairs with G (instead of A)

favor Gs where there should be As

46
Q

regulation of RNR responsible for…

A

balancing how much of any deoxyribonucleotide

uses tyrosine radical to pull oxygen off ribose at position 2 –> deoxyribose

47
Q

RNR is made of…

A

2 pairs of identical subunits (dimer of dimers)
R1 = large w/ 2 allosteric sites and active site
R2 = small, forms tyrosine radical

48
Q

2 allosteric sites of RNR

A

specificity site and activity site

49
Q

specificity site

A

fine tuning

controls which substrate binds and which deoxyribonucleotides are made

50
Q

binding of deoxypyrimidine triphosphates to specificity site of RNR –>

A

inhibit binding and reduction of pyrimidine diphosphates at active site, stimulate binding/reduction of purine diphosphates at active site

51
Q

activity site

A

controls whether or not RNR is active
on/off switch
ATP activates, dATP inactivates

52
Q

during thymidylate synthase activity (dUMP–>dTMP) ____ is produced

A

dihydrofolate (from tetrahydrofolate derivative)

must be converted back to tetrahydrofolate to keep synthesis occurring

53
Q

dihydrofolate –> tetrahydrofolate by

A

DHFR (dihydrofolate reductase)

54
Q

DHFR is target of ….

A

anticancer drugs that inhibit it

ex: methotrexate (resembles dihydrofolate, competitive inhibitor) and aminopterin

55
Q

DHFR inhibitors as a cancer treatment

A

cant make AMP, GMP,TMP
nucleotides critical for cancer cells –> stop cell division
- will also harm regular cell division
- high dose for cancer treatment then flushed out

56
Q

use compound that look like ___ as ___

A

look like folates as antibiotics

bacteria make own folate –> inhibit synthesis of folate

57
Q

breakdown of purine –>

A

xanthine –> uric acid via oxidation

58
Q

uric acid

A

from breakdown of purines
excretory role in birds and dalmations
not very water soluble –> gout
antioxidant, protective role against disease (ex: multiple sclerosis)

59
Q

treatment for gout

A

allopurinol, suicide inhibitor or xanthine oxidase enzyme

60
Q

HGPRT

A

direct salvage of guanine nucleotides and indirectly involved in salvage of adenine nucleotides through IMP and hypoxanthine

61
Q

Les-Nyhan syndrome

A

deficiency of HGPRT (for catabolism of guanine and adenine)

PRPP accumulates –> neurological problems

62
Q

deficiency in adenosine deaminase –>

A

severe combine immune deficiency

dATP accumulates in immune cells –> shutting off RNR and stopping division

Biochemistry (11 decks)

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