Quiz 1 (Nucleotide Metabolism) Flashcards
Nucleotides are ___ nucleosides.
Phosphorylated
- nucleoside = nitrogenous base + sugar
- nucleotide = nitrogenous base + sugar + phosphate(s)
What is used in DNA synthesis, but not RNA sysnthesis?
A. ADENINE B. GURANINE C. THYMINE D. CYTOSINE E. URACIL
C. THYMINE
*Uracil is used in RNA synthesis instead
What is the role of nucleotide sugars in the body?
A. They act as activated monosaccharide donors
B. They are used in glycogen synthesis
C. They are used in glycoprotein synthesis
D. All of the above
D.
The activation of ribose-5-phosphate is done by the enzyme ___ which requires ATP.
PRPP Synthetase
The committed step of purine synthesis is the formation of ___ from ___.
PRA / PRPP
The formation of IMP is inhibited by ___.
Methotrexate
The formation of ATP during purine synthesis also forms ___ which goes into the TCA cycle.
Fumarate
What is cross-regulation during nucleotide synthesis?
When the need of one nucleotide is coupled to another
Ex: AMP synthesis is stimulated by GTP synthesis
During pyrimidine synthesis, the ___ is built first and then PRPP is added.
Pyrimidine ring
The rate limiting step in pyrimidine synthesis involves the formation of ___ by CPS-II.
Carbamoyl phosphate
Disfunctions in UMP Synthetase can result in ___.
Orotic Aciduria
dUTP is highly regulated so that it ___.
Does not get incorporated into DNA
IMP —> ?
UMP —> ?
IMP —> purines (A/G)
UMP —> pyrimidines (T/C/U)
Defects in CPS-I result in ___ whereas defects in CPS-II result in ___.
Hyperammonemia / ?
- CPS-I = allows NH4+ to enter the Urea Cycle
- CPS-II = allows for the formation of pyrimidines
___ is a key antioxidant regulated by the formation of NADPH from the Pentose Phosphate Pathway.
Glutathione
Methotrexate can be used to inhibit ___ in rapidly dividing cancer cells by preventing the formation of ___.
DNA replication / dTMP
Sulfa drugs selectively disrupt DNA synthesis in ___ by inhibiting the formation of ___.
Bacteria / folate
Purine catabolism converges to form ___ which is largely converted to Uric Acid by the enzyme ___.
Xanthine / Xanthine Oxidase
*buildup of Uric Acid leads to Gout
___ can target Xanthine Oxidase to inactive it so that Uric Acid is not made in excess.
Allopurinol
Overproduction of ___ can lead to hemolytic anemia, while under production can lead to SCID (“bubble boy syndrome”).
ADA (Adenosine Deaminase)
*is responsible for deaminating Adenosine in purine catabolism
___ is the endpoint of purine catabolism.
Uric Acid
Limit dietary intake of ___ is used to treat gout.
Purines
*or use of Allopurinol to inhibit Xanthine Oxidase
Salvage pathways dominated de novo synthesis of ___.
Purines
- APRT regenerates AMP
- HGPRT regenerates GMP / IMP (deficiency —> Lesh-Nyhan Disease)
The activity of HGPRT contributes to ___ a disease characterized by self-destructive behavior.
Lesh-Nyhan Disease
*HGPRT regenerates purines excessively
The antiviral agent ___ structurally resembles guanine.
Acyclovir
*thymadine kinase from a virally-infected cell will use it to make DNA, but it will block DNA synthesis
In Severe Combined Immunodeficiency Disease (SCID), the enzyme ___ is deficient.
Adenosine Deaminase (ADA)
*deficiency in ADA results in buildup of dATP which inhibits ribonucleotide reductases (inhibits production of other dNTPs)
____ is an inhibitor of Xanthine Oxidase and is used to treat ___.
Allopurinol / GOUT
Treatment of Orotic Aciduria involves a uridine diet. How does this affect the disease?
- exogenous uridine can be converted to UMP by phosphotransferase
- UTP made from the exogenous uridine provides the substrate for CTP synthesis
- UTP made from the exogenous uridine can inhibit CPS-II
What is true of de novo synthesis of pyrimidine nucleotides?
A. All reactions take place in the cytosol
B. UMP and CMP are formed from a common intermediate
C. PRPP is required in the rate limiting step
D. UMP-mediated inhibition of OMP decarboxylase is the major mechanism of control
E. A free base is formed as the intermediate
E.
A. No - one step occurs in the mitochondria
B. No - UMP is eventually converted to CTP, however CMP is not part of that process
C. No - PRPP is the RLS for purine synthesis, not pyrimidine synthesis
D. No - OMP decarboxylation is done by UMP Synthase which is not the main regulatory step (CPS-II is the major step regulated by UMP)
Deoxyribonucleotides are synthesized by an enzyme system involving ___.
Thioredoxin
