Lecturio - Nucleotide metabolism Flashcards
1
Q
Cells make nucleotides by 2 pathways which are ___ and ___
A
de novo and salvage synthesis.
2
Q
Are purines made separately from pyrimidines?
A
Yes!
3
Q
dNTPs are made from _____
A
ribonucleoside diphosphates.
4
Q
Thymidine nucleotides are made from ____
A
uridine nucleotides.
5
Q
Purine atom sources
-> Identify sources
A
1/ CO2
2/ Glutamine
6
Q
Purine atom sources
-> Identify sources
A
Glycine
7
Q
Purine atom sources
-> Identify sources
A
N10-Formyl-THF
8
Q
Pyrimidine atom sources
-> Identify sources
A
9
Q
Nucleotides made from ______
A
very simple molecules
- amino acids, one carbon donors, CO2
10
Q
Pyrimidine rings are synthesized separate from ____ and then attached.
A
sugar
11
Q
Synthesis very tightly regulated imbalances favor _____
A
mutation
12
Q
Purine synthesis begins on ___
A
the ribose sugar.
13
Q
Nucleotides made from ______
A
very simple molecules
- amino acids, one carbon donors, CO2
14
Q
De novo Purine Metabolism
-> _______ is the starting point
A
Ribose-5-phosphate
15
Q
De novo Purine Metabolism
-> Identify
A
Adenylosuccinate
16
Q
De novo Purine Metabolism
-> Identify
A
1/ Glutamine
2/ Glutamate
17
Q
De novo Purine Metabolism
-> Identify
A
1/ AMP
2/ GMP
18
Q
De novo Purine Metabolism
-> Identify
A
19
Q
De novo Purine Metabolism
-> Identify 1
A
1/ IMP
2/ XMP
20
Q
De novo Purine Metabolism
-> Ribose-5-phosphate is the starting point
-> ____ made, then aminated using glutamine
A
PRPP
21
Q
De novo Purine Metabolism
-> Ribose-5-phosphate is the starting point
-> PRPP made, then aminated using ___
A
glutamine
22
Q
De novo Purine Metabolism
-> Identify
A
1/ PRPP Synthetase
2/ PRPP Amidotransferase
23
Q
De novo Purine Metabolism
-> Identify
A
1/ R5P
2/ PRPP
3/ Phosphoribosylamine
24
Q
How is a Purine Ring built?
A
Phosphoribosylamine with the addition of Glycine at the start
-> Then being added with Aspartate
25
Building a Purine Ring
-> Identify
1/ Phosphoribosylamine
2/ Glycine
3/ Aspartate
26
De novo Purine Metabolism
-> Identify
1/ ATP
2/ AMP
27
Paths to Adenine Nucleotides
-> Identify
1/ Adenylosuccinate synthetase
2/ Adenylate kinase
3/ NDPK - Nucleoside-diphosphate kinase
28
Paths to Adenine Nucleotides
-> Identify
1/ aspartate
2/ fumarate
29
Paths to Guanine Nucleotides
-> Identify
1/ IMP dehydrogenase
2/ GMP kinase
3/ NDPK - Nucleoside-diphosphate kinase
30
Paths to Guanine Nucleotides
-> Identify
1/ NAD+
2/ NADH
3/ XMP
31
Purine de novo Metabolism Regulation
-> What are the 4 purine synthesis enzymes involved?
1/ PRPP synthetase
2/ PRPP amidotransferase
3/ IMP dehydrogenase
4/ Adenylosuccinate synthetase
32
De novo Purine Metabolism
-> PRPP synthetase inhibited by __ and __
high phosphate and ADP
33
De novo Purine Metabolism
- Partly inhibited by ___ or ____
- Fully inhibited by ___ & ___
- AMP or GMP
- AMP and GMP
34
De novo Purine Metabolism
-> IMP dehydrogenase inhibited by ___
GMP
35
De novo Purine Metabolism
-> Adenylosuccinate synthetase inhibited by ___
AMP
36
Purine de novo Metabolism Regulation (black arrows)
-> Identify
37
Pyrimidine de novo Metabolism
->
1/ Ring built first, then attached to ribose-5-P of PRPP
2/ 6 steps from bicarbonate to UMP
38
Pyrimidine de novo Metabolism
-> Identify
* Ring built first, then attached to ribose-5-P of PRPP
* 6 steps from bicarbonate to UMP
39
Pyrimidine de novo Metabolism
-> Identify
ATCase = Aspartate Carbamoyltransferase
40
ATCase Reaction
-> Identify
1/ ATP (Purine)
2/ CTP (Pyrimidine)
41
Pyrimidine de novo Metabolism
-> Identify
OMP Decarboxylase
42
OMP Decarboxylase uses which cofactors/coenzymes?
Enzyme uses no cofactors/coenzymes.
43
Synthesis of UTP and CTP
-> Identify
1/ UMP/CMP kinase
2/ NDPK
3/ CTP synthetase
44
Synthesis of UTP and CTP
-> Identify
1/ Glutamine + ATP
2/ Glutamate + ADP + Pi
45
CTP Synthetase
-> balances ____ and ___
purines and pyrimidines
46
CTP Synthetase
(1) Inhibited by ___ (2 things)
(2) Activated by _____
1 - phosphorylation at 2 sites; CTP
2 - GTP
47
Nucleotides in nucleic acids are ___ (monophosphates/diphosphates/triphosphates)
monophosphates
48
Breakdown of RNA and DNA taken up by cell starts with ____
nucleases
49
Catabolism of Guanine Nucleotides
-> Identify these enzymes
1/ RNase
2/ Purine nucleotidase
50
Catabolism of Guanine Nucleotides
-> Identify
1/ GMP
2/ Guanosine
3/ Guanine
4/ Ribose-1-P
51
Catabolism of Guanine Nucleotides
-> Identify
1/ GMP
2/ Guanosine
3/ Guanine
4/ Ribose-1-P
52
Catabolism of Guanine Nucleotides
-> Identify the enzyme in the last step
Purine nucleoside phosphorylase
53
Catabolism of Adenine Nucleotides
-> Identify these enzymes
1/ RNase
2/ Purine nucleotidase
54
Catabolism of Adenine Nucleotides
-> identify these enzymes
1/ AMP deaminase
2/ Nucleotidase
3/ Purine nucleoside phosphorylase
55
Catabolism of Adenine Nucleotides
-> identify these enzymes
1/ AMP deaminase
2/ Nucleotidase
3/ Purine nucleoside phosphorylase
56
Catabolism of Adenine Nucleotides
-> Identify this enzyme
Adenosine deaminase
57
Catabolism of Adenine Nucleotides
-> Identify
1/ AMP
2/ Adenosine
58
Catabolism of Adenine Nucleotides
-> Identify
1/ Inosinic acid (IMP)
2/ Ionsine
59
Catabolism of Adenine Nucleotides
-> Identify 1 & 2
1/ Ribose-1-P
2/ Hypoxanthine
60
Catabolism of Guanine and Hypoxanthine
-> High concentrations of ___ cause gout.
uric acid
61
Catabolism of Guanine and Hypoxanthine
-> Identify
1/ Hypoxanthine
2/ Xanthine
3/ Uric acid
62
Catabolism of Guanine and Hypoxanthine
-> identify
Guanine
63
Xanthine oxidase can be inhibited by ____
allopurinol
64
The role of Allopurinol
Allopurinol forces salvage and prevents formation of uric acid.
- Inhibit xanthine oxidase
65
Purine Nucleotide Salvage
-> Identify the enzyme
Adenine Phosphoribosyltransferase
66
Purine Nucleotide Salvage
-> Identify the enzyme
Hypoxanthine/guanine Phosphoribosyltransferase
67
Purine Nucleotide Salvage
-> Identify this enzyme
Hypoxanthine/guanine Phosphoribosyltransferase
68
Purine Nucleotide Salvage
-> Identify
1/ IMP
2/ AMP
3/ GMP
69
Purine Nucleotide Salvage
-> Identify this molecule
PRPP
70
Purine Nucleotide Salvage
-> Deficiency of Hypoxanthine/guanine Phosphoribosyltransferase can cause ___
Lesch-Nyhan syndrome
71
Pyrimidine Catabolism and Salvage Reactions
-> Do catabolic and salvage pathways for pyrimidines overlap?
YES!
72
Pyrimidine Catabolism and Salvage Reactions
-> The role of nucleosidases
It can use water to hydrolyze bases from sugars instead of phosphorylases
73
Pyrimidine Catabolism and Salvage Reactions
-> Breakdown converges on ____
production of uracil
74
Pyrimidine Catabolism and Salvage Reactions
-> Which Pyrimidine nucleotides handled separately?
Thymidine
75
Catabolism of Uracil and Thymine
-> Identify 1 & 2
1/ Dihydrothymine
2/ 3 -aminoisobutyrate
76
Catabolism of Uracil and Thymine
-> Identify
1/ Dihydrouracil
2/ Beta-alanine
77
Deoxyribonucleotide Synthesis
-> Deoxyribonucleotides are made from ____
ribonucleoside diphosphates ADP, CDP, GDP, and UDP.
78
The enzyme responsible for Deoxyribonucleotide Synthesis is ____
ribonucleotide reductase.
79
Deoxyribonucleotide Synthesis
-> Identify
1/ Ribonucleotide reductase reduced
2/ Ribonucleotide reductase oxidized
a/ Thioredoxin oxidized
b/ Thioredoxin reduced
80
Structure of Ribonucleotide Reductase
* Ribonucleotide reductase (RNR) has 2 subunits large and small.
* Large subunit (R1) has 2 allosteric sites and the active site.
* Small subunit (R2) has a tyrosine that gets radicalized in the reaction mechanism.
81
The role of Ribonucleotide Reductase
It controls balance of deoxyribonucleotides with complex allosteric controls.
82
Nucleotide Metabolism
-> Name 4 molecule that can bind to substrate specificity site
ATP
dATP
dGTP
dTTP
83
Nucleotide Metabolism
-> Name 2 molecules that can bind to activity site
dATP
ATP
84
Nucleotide Metabolism
-> Name 4 molecules that can bind to substrate specificity site
UDP
CDP
ADP
GDP
85
Which molecule bind to the activity site will inactivate the enzyme?
dATP
86
Which molecule bind to the activity site will activate the enzyme?
ATP
87
Nucleotide Metabolism
-> The binding of dTTP to the substrate specificity site will favor production of which molecule at active site?
GDP
88
Nucleotide Metabolism
-> The binding of dGTP to the substrate specificity site will favor production of which molecule at active site?
ADP
89
Nucleotide Metabolism
-> The binding of dGTP to the substrate specificity site will favor production of which molecule at active site?
ADP
90
Nucleotide Metabolism
-> The binding of dATP to the substrate specificity site will favor production of which molecule at active site?
CTP
91
Thymidine Metabolism
-> dNDPs are converted to dNTPs (including dUTP) by ____.
NDPK
92
Thymidine Metabolism
-> Thymidine nucleotides are made from _____.
uridine nucleotides
93
dUTP can be used by____ to make DNA.
DNA polymerase
94
Thymidine Metabolism
-> Identify
1/ RNR
2/ NDPK
3/ dUTPase
95
Thymidine Metabolism
-> Identify
1/ Thymidylate synthase
2/ dMPT Kinase
3/ NDPK
96
Example of a suicide inhibitor of thymidylate synthase
5-Fluorouracil anticancer treatment
97
Recycling of Folates
-> Identify
1/ Dihydrofolate reductase
2/ Serine hydroxymethyltransferase
98
Recycling of Folates
-> Identify
1/ Dihydrofolate
2/ Tetrahydrofolate
3/ 5,10 - methylenetetrahydrofolate
99
Recycling of Folates
-> An example of inhibitor of Dihydrofolate reductase
Methotrexate
100
Recycling of Folates
-> An example of inhibitor of Dihydrofolate reductase
Methotrexate
101
Recycling of Folates
-> Characteristics of Methotrexate
* Methotrexate is a competitive inhibitor of DHFR.
* Used for chemotherapy
* Effective against rapidly dividing cells
102
Nucleoside Analogs get phosphorylated inside cells by ___
salvage systems
103
2 examples of Deoxyadenosine Analogs
1/ Didanosine (ddI)
2/ Vidarabine (Ara-A)
104
Deoxyadenosine Analogs
-> 3 characteristics of Didanosine (ddI)
* Can be phosphorylated and used by DNA polymerase
* Terminates any DNA chain
* Anti-HIV
105
Deoxyadenosine Analogs
-> 2 characteristics of Didanosine (ddI)
* Competitive Inhibitor of dATP for viral DNA polymerases
* Antiviral
106
An example of Adenosine Analogs
BCX 4430
