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BB451 exam 2 - Nucleotide Metabolism Flashcards

(62 cards)

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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
purine synthesis uses atoms from....
aspartate, glycine, glutamine, CO2, tetrahydrofolate derivate (single C donor)
26
most important regulatory enzyme in purine synthesis
PRPP amidotransferase controls purine production - slows when one nucleotide is too high in concentration balance between AMP and GMP
27
PRPP amidotransferase inhibited by
fully by AMP and GMP (end products) | partly when only one is present
28
purine synthesis begins with
PRPP - ribose ring
29
single carbon donor in purine synthesis
folate
30
shortage of folate in pregnancy..
--> neural tube defects (70% reduction by supplementation)
31
first purine like intermediate
IMP (I in some transfer RNAs) branch on synthesis of GMP and AMP purine link base hypoxanthine linked to ribose
32
process of making IMP
fumarate released (connecting to CAS)
33
IMP oxidation -->
GMP | inhibited by GMP, energy from ATP
34
IMP --> AMP
aspartic acid donates amine fumarate released inhibited by AMP, energy from GTP
35
balance between AMP and GTP
- PRPP amidotransferase - GMP production inhibited by GMP, energy from ATP - AMP production inhibited by AMP, energy from GTP
36
AMP and GMP --> ADP and GDP by
AMP kinase and GMP kinase
37
ADP and GDP --> ATP and GTP by
NDPK
38
deoxyribonucleotides made starting with..
RNR (ribonucleotide reductase) catalyzes ribonucleoside diposphates --> deoxyribonucleoside diphosphates ex: ADP ---> dADP
39
RNR works on...
all ribonucleoside diphosphates
40
dADP --> dATP via
NDPK (all nucleoside diphosphates)
41
making thymine nucleotides (first 2 steps)
UDP--> dUDP via RNR | dUDP --> dUTP via NDPK
42
making thymine nucleotides...dUTP --> dUMP by
dUTPase
43
making thymine nucleotides dUMP --> dTMP by
thymidylate synthase - requires folate to put methyl group onto U to make T
44
dTMP-->
dTDP --> dTTP via NDPK
45
why T in DNA not U
u will form stable base pairs with G (instead of A) | favor Gs where there should be As
46
regulation of RNR responsible for...
balancing how much of any deoxyribonucleotide | uses tyrosine radical to pull oxygen off ribose at position 2 --> deoxyribose
47
RNR is made of...
2 pairs of identical subunits (dimer of dimers) R1 = large w/ 2 allosteric sites and active site R2 = small, forms tyrosine radical
48
2 allosteric sites of RNR
specificity site and activity site
49
specificity site
fine tuning | controls which substrate binds and which deoxyribonucleotides are made
50
binding of deoxypyrimidine triphosphates to specificity site of RNR -->
inhibit binding and reduction of pyrimidine diphosphates at active site, stimulate binding/reduction of purine diphosphates at active site
51
activity site
controls whether or not RNR is active on/off switch ATP activates, dATP inactivates
52
during thymidylate synthase activity (dUMP-->dTMP) ____ is produced
dihydrofolate (from tetrahydrofolate derivative) | must be converted back to tetrahydrofolate to keep synthesis occurring
53
dihydrofolate --> tetrahydrofolate by
DHFR (dihydrofolate reductase)
54
DHFR is target of ....
anticancer drugs that inhibit it | ex: methotrexate (resembles dihydrofolate, competitive inhibitor) and aminopterin
55
DHFR inhibitors as a cancer treatment
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
use compound that look like ___ as ___
look like folates as antibiotics | bacteria make own folate --> inhibit synthesis of folate
57
breakdown of purine -->
xanthine --> uric acid via oxidation
58
uric acid
from breakdown of purines excretory role in birds and dalmations not very water soluble --> gout antioxidant, protective role against disease (ex: multiple sclerosis)
59
treatment for gout
allopurinol, suicide inhibitor or xanthine oxidase enzyme
60
HGPRT
direct salvage of guanine nucleotides and indirectly involved in salvage of adenine nucleotides through IMP and hypoxanthine
61
Les-Nyhan syndrome
deficiency of HGPRT (for catabolism of guanine and adenine) | PRPP accumulates --> neurological problems
62
deficiency in adenosine deaminase -->
severe combine immune deficiency | dATP accumulates in immune cells --> shutting off RNR and stopping division

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