Lecturio - Nucleotide metabolism Flashcards
Cells make nucleotides by 2 pathways which are ___ and ___
de novo and salvage synthesis.
Are purines made separately from pyrimidines?
Yes!
dNTPs are made from _____
ribonucleoside diphosphates.
Thymidine nucleotides are made from ____
uridine nucleotides.
Purine atom sources
-> Identify sources
1/ CO2
2/ Glutamine
Purine atom sources
-> Identify sources
Glycine
Purine atom sources
-> Identify sources
N10-Formyl-THF
Pyrimidine atom sources
-> Identify sources
Nucleotides made from ______
very simple molecules
- amino acids, one carbon donors, CO2
Pyrimidine rings are synthesized separate from ____ and then attached.
sugar
Synthesis very tightly regulated imbalances favor _____
mutation
Purine synthesis begins on ___
the ribose sugar.
Nucleotides made from ______
very simple molecules
- amino acids, one carbon donors, CO2
De novo Purine Metabolism
-> _______ is the starting point
Ribose-5-phosphate
De novo Purine Metabolism
-> Identify
Adenylosuccinate
De novo Purine Metabolism
-> Identify
1/ Glutamine
2/ Glutamate
De novo Purine Metabolism
-> Identify
1/ AMP
2/ GMP
De novo Purine Metabolism
-> Identify
De novo Purine Metabolism
-> Identify 1
1/ IMP
2/ XMP
De novo Purine Metabolism
-> Ribose-5-phosphate is the starting point
-> ____ made, then aminated using glutamine
PRPP
De novo Purine Metabolism
-> Ribose-5-phosphate is the starting point
-> PRPP made, then aminated using ___
glutamine
De novo Purine Metabolism
-> Identify
1/ PRPP Synthetase
2/ PRPP Amidotransferase
De novo Purine Metabolism
-> Identify
1/ R5P
2/ PRPP
3/ Phosphoribosylamine
How is a Purine Ring built?
Phosphoribosylamine with the addition of Glycine at the start
-> Then being added with Aspartate
Building a Purine Ring
-> Identify
1/ Phosphoribosylamine
2/ Glycine
3/ Aspartate
De novo Purine Metabolism
-> Identify
1/ ATP
2/ AMP
Paths to Adenine Nucleotides
-> Identify
1/ Adenylosuccinate synthetase
2/ Adenylate kinase
3/ NDPK - Nucleoside-diphosphate kinase
Paths to Adenine Nucleotides
-> Identify
1/ aspartate
2/ fumarate
Paths to Guanine Nucleotides
-> Identify
1/ IMP dehydrogenase
2/ GMP kinase
3/ NDPK - Nucleoside-diphosphate kinase
Paths to Guanine Nucleotides
-> Identify
1/ NAD+
2/ NADH
3/ XMP
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
De novo Purine Metabolism
-> PRPP synthetase inhibited by __ and __
high phosphate and ADP
De novo Purine Metabolism
- Partly inhibited by ___ or ____
- Fully inhibited by ___ & ___
- AMP or GMP
- AMP and GMP
De novo Purine Metabolism
-> IMP dehydrogenase inhibited by ___
GMP
De novo Purine Metabolism
-> Adenylosuccinate synthetase inhibited by ___
AMP
Purine de novo Metabolism Regulation (black arrows)
-> Identify
Pyrimidine de novo Metabolism
->
1/ Ring built first, then attached to ribose-5-P of PRPP
2/ 6 steps from bicarbonate to UMP
Pyrimidine de novo Metabolism
-> Identify
- Ring built first, then attached to ribose-5-P of PRPP
- 6 steps from bicarbonate to UMP
Pyrimidine de novo Metabolism
-> Identify
ATCase = Aspartate Carbamoyltransferase
ATCase Reaction
-> Identify
1/ ATP (Purine)
2/ CTP (Pyrimidine)
Pyrimidine de novo Metabolism
-> Identify
OMP Decarboxylase
OMP Decarboxylase uses which cofactors/coenzymes?
Enzyme uses no cofactors/coenzymes.
Synthesis of UTP and CTP
-> Identify
1/ UMP/CMP kinase
2/ NDPK
3/ CTP synthetase
Synthesis of UTP and CTP
-> Identify
1/ Glutamine + ATP
2/ Glutamate + ADP + Pi
CTP Synthetase
-> balances ____ and ___
purines and pyrimidines
CTP Synthetase
(1) Inhibited by ___ (2 things)
(2) Activated by _____
1 - phosphorylation at 2 sites; CTP
2 - GTP
Catabolism of Guanine Nucleotides
-> Identify these enzymes
1/ RNase
2/ Purine nucleotidase
Catabolism of Guanine Nucleotides
-> Identify
1/ GMP
2/ Guanosine
3/ Guanine
4/ Ribose-1-P
Catabolism of Guanine Nucleotides
-> Identify
1/ GMP
2/ Guanosine
3/ Guanine
4/ Ribose-1-P
Catabolism of Guanine Nucleotides
-> Identify the enzyme in the last step
Purine nucleoside phosphorylase
Catabolism of Adenine Nucleotides
-> Identify these enzymes
1/ RNase
2/ Purine nucleotidase
Catabolism of Adenine Nucleotides
-> identify these enzymes
1/ AMP deaminase
2/ Nucleotidase
3/ Purine nucleoside phosphorylase
Catabolism of Adenine Nucleotides
-> identify these enzymes
1/ AMP deaminase
2/ Nucleotidase
3/ Purine nucleoside phosphorylase
Catabolism of Adenine Nucleotides
-> Identify this enzyme
Adenosine deaminase
Catabolism of Adenine Nucleotides
-> Identify
1/ AMP
2/ Adenosine
Catabolism of Adenine Nucleotides
-> Identify
1/ Inosinic acid (IMP)
2/ Ionsine
Catabolism of Adenine Nucleotides
-> Identify 1 & 2
1/ Ribose-1-P
2/ Hypoxanthine
Catabolism of Guanine and Hypoxanthine
-> High concentrations of ___ cause gout.
uric acid
Catabolism of Guanine and Hypoxanthine
-> Identify
1/ Hypoxanthine
2/ Xanthine
3/ Uric acid
Catabolism of Guanine and Hypoxanthine
-> identify
Guanine
The role of Allopurinol
Allopurinol forces salvage and prevents formation of uric acid.
- Inhibit xanthine oxidase
Purine Nucleotide Salvage
-> Identify the enzyme
Adenine Phosphoribosyltransferase
Purine Nucleotide Salvage
-> Identify the enzyme
Hypoxanthine/guanine Phosphoribosyltransferase
Purine Nucleotide Salvage
-> Identify this enzyme
Hypoxanthine/guanine Phosphoribosyltransferase
Purine Nucleotide Salvage
-> Identify
1/ IMP
2/ AMP
3/ GMP
Purine Nucleotide Salvage
-> Identify this molecule
PRPP
Purine Nucleotide Salvage
-> Deficiency of Hypoxanthine/guanine Phosphoribosyltransferase can cause ___
Lesch-Nyhan syndrome
Pyrimidine Catabolism and Salvage Reactions
-> Do catabolic and salvage pathways for pyrimidines overlap?
YES!
Pyrimidine Catabolism and Salvage Reactions
-> The role of nucleosidases
It can use water to hydrolyze bases from sugars instead of phosphorylases
Pyrimidine Catabolism and Salvage Reactions
-> Breakdown converges on ____
production of uracil
Pyrimidine Catabolism and Salvage Reactions
-> Which Pyrimidine nucleotides handled separately?
Thymidine
Catabolism of Uracil and Thymine
-> Identify 1 & 2
1/ Dihydrothymine
2/ 3 -aminoisobutyrate
Catabolism of Uracil and Thymine
-> Identify
1/ Dihydrouracil
2/ Beta-alanine
The enzyme responsible for Deoxyribonucleotide Synthesis is ____
ribonucleotide reductase.
Deoxyribonucleotide Synthesis
-> Identify
1/ Ribonucleotide reductase reduced
2/ Ribonucleotide reductase oxidized
a/ Thioredoxin oxidized
b/ Thioredoxin reduced
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.
The role of Ribonucleotide Reductase
It controls balance of deoxyribonucleotides with complex allosteric controls.
Nucleotide Metabolism
-> Name 4 molecule that can bind to substrate specificity site
ATP
dATP
dGTP
dTTP
Nucleotide Metabolism
-> Name 2 molecules that can bind to activity site
dATP
ATP
Nucleotide Metabolism
-> Name 4 molecules that can bind to substrate specificity site
UDP
CDP
ADP
GDP
Which molecule bind to the activity site will inactivate the enzyme?
dATP
Which molecule bind to the activity site will activate the enzyme?
ATP
Nucleotide Metabolism
-> The binding of dTTP to the substrate specificity site will favor production of which molecule at active site?
GDP
Nucleotide Metabolism
-> The binding of dGTP to the substrate specificity site will favor production of which molecule at active site?
ADP
Nucleotide Metabolism
-> The binding of dGTP to the substrate specificity site will favor production of which molecule at active site?
ADP
Nucleotide Metabolism
-> The binding of dATP to the substrate specificity site will favor production of which molecule at active site?
CTP
Thymidine Metabolism
-> dNDPs are converted to dNTPs (including dUTP) by ____.
NDPK
Thymidine Metabolism
-> Thymidine nucleotides are made from _____.
uridine nucleotides
Thymidine Metabolism
-> Identify
1/ RNR
2/ NDPK
3/ dUTPase
Thymidine Metabolism
-> Identify
1/ Thymidylate synthase
2/ dMPT Kinase
3/ NDPK
Example of a suicide inhibitor of thymidylate synthase
5-Fluorouracil anticancer treatment
Recycling of Folates
-> Identify
1/ Dihydrofolate reductase
2/ Serine hydroxymethyltransferase
Recycling of Folates
-> Identify
1/ Dihydrofolate
2/ Tetrahydrofolate
3/ 5,10 - methylenetetrahydrofolate
Recycling of Folates
-> An example of inhibitor of Dihydrofolate reductase
Methotrexate
Recycling of Folates
-> An example of inhibitor of Dihydrofolate reductase
Methotrexate
Recycling of Folates
-> Characteristics of Methotrexate
- Methotrexate is a competitive inhibitor of DHFR.
- Used for chemotherapy
- Effective against rapidly dividing cells
Nucleoside Analogs get phosphorylated inside cells by ___
salvage systems
2 examples of Deoxyadenosine Analogs
1/ Didanosine (ddI)
2/ Vidarabine (Ara-A)
Deoxyadenosine Analogs
-> 3 characteristics of Didanosine (ddI)
- Can be phosphorylated and used by DNA polymerase
- Terminates any DNA chain
- Anti-HIV
Deoxyadenosine Analogs
-> 2 characteristics of Didanosine (ddI)
- Competitive Inhibitor of dATP for viral DNA polymerases
- Antiviral
An example of Adenosine Analogs
BCX 4430
