Nucleotide Metabolism (last quiz) Flashcards
Nucleic acids can be either….
DNA or RNA
What is the monomer of nucleic acids?
nucleotides
What makes up a nucleotide?
sugar, base, and phosphate
What are the 2 types of sugars in nucleotides?
ribose or deoxyribose
What is the formula for ribose?
C5H10O5
What is the formula for deoxyribose?
C5H10O4
What enzyme makes RNA?
RNA polymerase
RNA polymerase uses DNA as a template in transcription
What enzyme makes DNA?
DNA polymerase
DNA polymerase uses DNA as template during DNA replication
What pathway is the source of phosphopentose?
PPP
What is the first step to making phosphopentose?
PPP
After PPP pathway, ribose 5 phosphate is made. ATP is used along with _______________________________ to make phosphoribosyl pyrophosphate (PRPP)
ribose phosphate pyrophosphokinase
What is the active form of ribose 5 phosphate?
phosphoribosyl pyrophosphate (PRPP)
phosphoribosyl pyrophosphate (PRPP) is converted to deoxyribose with ____________________, thioredoxin or glutathione (GSH), and NADPH
ribonucleotide reductase
note: this is a reduction reaction, there is a loss of oxygen and NADPH provides H to thioredoxin or GSH, which then provides H to make deoxyribose
What is a nucleoside?
base + sugar (no phosphate, nucleotides are with phosphate)
What does ribonucleotide reductase require?
GSH or thioredoxin
and NADPH
What is the most important antioxidant?
NADPH
What are the 2 types of bases?
purines and pyrimidines
How many ring structures are there in pyrimidines?
1 ring
(longer name but smaller structure than purines)
What are the 3 types of pyrimidines?
CUT
1) cytosine
2) uracil
3) thymine
Which pyrimidine is the simplest one?
uracil
Which pyrimidine is made when NH2 is added to uracil?
cytosine
Where does the NH2 come from in cytosine?
glutamine
Which pyrimidine is made when CH3 is added to uracil?
thymine
Where does the methyl group come from in thymine?
folate (vit B9)
Which vitamin is important for DNA synthesis?
Vit B9/ folate bc its needed to make thymine
Folate is a _________ donor
methyl
Pyrimidine atoms come from where?
-glutamine
-aspartate
-CO2
What are the 2 pyrimidines used to synthesize DNA?
C and T
What are the 2 pyrimidines used to synthesize RNA?
C and U
What does de novo mean?
from scratch
De novo pyrimidine synthesis is similar to which cycle?
urea cycle
In de novo pyrimidine biosynthesis, CO2 and glutamine bind with ATP to make __________________
carbamoyl phosphate (CAP)
In de novo pyrimidine biosynthesis, CO2 and glutamine bind with ATP to make carbamoyl phosphate (CAP). What enzyme does this?
carbamoyl phosphate synthetase 2 (CPS2) WHICH IS THE RLE in this pathway!!!
In de novo pyrimidine biosynthesis, CO2 and glutamine bind with ATP to make carbamoyl phosphate (CAP) with CPS2 (the RLE of this pathway). CAP will then bind with what to eventually form a ring structure called orotic acid (OA)?
aspartate
In de novo pyrimidine biosynthesis, CO2 and glutamine bind with ATP to make carbamoyl phosphate (CAP) with CPS2 (the RLE of this pathway). CAP will then bind with asp to eventually form a ring structure called orotic acid (OA). OA then bind to what to make OMP?
PRPP
What is the 1st ring structure in de novo pyrimidine biosynthesis?
orotic acid (also known as orotate or OA)
In de novo pyrimidine biosynthesis, CO2 and glutamine bind with ATP to make carbamoyl phosphate (CAP) with CPS2 (the RLE of this pathway). CAP will then bind with asp to eventually form a ring structure called orotic acid (OA). OA then bind to PRPP to make OMP. From here, OMP will eventually make what?
uridime monophosphate (UMP)
In de novo pyrimidine biosynthesis, CO2 and glutamine bind with ATP to make carbamoyl phosphate (CAP) with CPS2 (the RLE of this pathway). CAP will then bind with asp to eventually form a ring structure called orotic acid (OA). OA then bind to PRPP to make OMP. From here, OMP will eventually make UMP. From here, UMP will use ATP and kinase to make _______
UDP
In de novo pyrimidine biosynthesis, CO2 and glutamine bind with ATP to make carbamoyl phosphate (CAP) with CPS2 (the RLE of this pathway). CAP will then bind with asp to eventually form a ring structure called orotic acid (OA). OA then bind to PRPP to make OMP. From here, OMP will eventually make UMP. Then, UMP will use ATP and kinase to make UDP. UDP can now either make CTP or dTMP.
If UDP makes CTP, then it first will need ATP and kinase to make UTP. From UTP, it will use ATP, _____________, and ____________ to make CTP
glutamine, CTP synthase
In de novo pyrimidine biosynthesis, CO2 and glutamine bind with ATP to make carbamoyl phosphate (CAP) with CPS2 (the RLE of this pathway). CAP will then bind with asp to eventually form a ring structure called orotic acid (OA). OA then bind to PRPP to make OMP. From here, OMP will eventually make UMP. Then, UMP will use ATP and kinase to make UDP. UDP can now either make CTP or dTMP.
If UDP makes dTMP then it will need to be converted first to dUDP. UDP uses NADPH or GSH with _________________ to make dUDP
ribonucleotide reductase
In de novo pyrimidine biosynthesis, CO2 and glutamine bind with ATP to make carbamoyl phosphate (CAP) with CPS2 (the RLE of this pathway). CAP will then bind with asp to eventually form a ring structure called orotic acid (OA). OA then bind to PRPP to make OMP. From here, OMP will eventually make UMP. Then, UMP will use ATP and kinase to make UDP. UDP can now either make CTP or dTMP.
If UDP makes dTMP then it will need to be converted first to dUDP. UDP uses NADPH or GSH with ribonucleotide reductase to make dUDP. dUDP will then use water to break off a phosphate and make dUMP. dUMP will then use _____________ to make dTMP
methyl THF (methyl tetrahydrofolate)
Which enzyme converts DHF to methyl THF? What does this enzyme require?
DHF reductase, requires folic acid
Anti-cancer drugs are targeting the enzymes of which pyrimidine when being synthesized?
thymine
(DHF reductase is inhibited by many anticancer chemotherapies such as methotrexate)
T/F: in de novo pyrimidine biosynthesis, pyrimidine bases are constructed first and then added to PRPP
true
CPS1 is a part of which cycle?
urea cycle
CPS2 is a part of which cycle?
de novo pyrimidine biosynthesis
Where is CPS1 located?
in mitochondria
Where is CPS2 located?
in cytoplasm
What is the difference between urea cycle and pyrimidine biosynthesis in the catalytic reaction?
urea cycle uses glutamate, while pyrimidine biosynthesis uses glutamine
The formation of dTTP is critical for…
DNA synthesis
Methyl THF is essential for ______________ synthesis, which are necessary for cell proliferation and cell growth
purine and thymidylate
Purines have how many ring structures?
2 ring structure
(shorter name than pyrimidine, bit larger structure)
What are more difficult to synthesize- purines or pyrimidines? Why?
purines because they have 2 rings
What are the 2 types of purines?
pure as gold
1) adenine
2) guanine
Which purines require folate?
all purines do- so adenine and guanine
Which purines are used in both DNA and RNA?
all purines do- so adenine and guanine
Collagen is rich in which AA?
glycine
(collagen is most abundant in skin and bone, so when you eat joints, bones, and skin from animals then you get collagen and glycine in your diet)
What are the sources of the nitrogen and carbon atoms of the purine ring?
-aspartate
-glutamine
-CO2
-glycine
-THF
What does salvage mean?
recycled, not synthesized from scratch
90% of hypoxanthine and ___________ gets broken down with HGPRT, and the other 10% becomes _________ and gets completely broken down
guanine, uric acid
What are the 2 types of gout?
1) genetic= lesch nyhan syndrome
2) regular gout
Why do the elderly commonly have gout?
because HGPRT is not working as it should as you get older
also alcohol and high fructose corn syrup makes it works
Purine bases are generally recycled since they are….
energetically expensive
Adenine and guanine bases are recycled by adding them back to…
PRPP
What is lesch nyhan syndrome?
-genetic gout, sometimes called juvenile gout bc symptoms start after birth
-caused by congenital loss of HGPRT
-uric acid will get overproduced and cause progressive and severe mental retardation
Gout is a ________ metabolism disease
purine
What is the purine nucleotide salvage pathway?
If HGPRT is not functioning properly, then more than 10% of hypoxanthine and guanine will become uric acid and this causes….
gout
Gout frequently accompanies other medical problems such as…
-abdominal obesity
-HTN
-insulin resistence
-abnormal lipid levels
Gout usually attacks the big toes first causing acute inflammatory ___________, which eventually leads to crystals precipitating in the kidneys and results in kidney stone formation
arthritis
A definitive diagnosis of gout is based upon the identification of
needle shaped crystals in synovial fluid (this is how regular gout is differentiated from genetic gout)
What is a classic feature of gout?
hyperuricemia
What can trigger gout?
-alcohol
-purine rich foods like seafood
-fructose sweetened drinks/food
-meat
-physical trauma or surgeries
What is the treatment for gout?
NSAIDs to inhibit macrophages
De novo purine biosynthesis is regulated by feedback inhibition. The rate limiting step is catalyzed by PRPP amidotransferase, which transfers an amine from glutamine to ribose. This enzyme is under feedback regulation from products of purine synthesis. What inhibits this enzyme?
-ATP, ADP, or AMP
-GTP, GDP, or GMP
-IMP
T/F: urea is a major nitrogen waste bc AAs and pyrimidines break down to urea
true
What do purines degrade to?
uric acid
Is uric acid soluble or insoluble
insoluble
this is why high amounts of purine in the diet will lead to crystals of uric acid and cause gout
The 1st step in removing adenine is catalyzed by ______________________. Genetic deficits in this enzyme causes the accumulation of adenine which leads to immunodeficiency known as SCID
adenosine deaminase
(purine breakdown is inhibited, but a BM transplant should help with B/T cell production)
Pyrimidines are broken down to a carbon skeleton and urea which is similar to….
AA degradation
Urea is major nitrogen waste in the…
urine
What enzyme adds phosphate to ribose and deoxyribose of monophosphate nucleosides?
nucleoside monophosphate kinases
What AAs are essential precursors for purines and pyrimidines?
glutamine and aspartate
What condition is a precursor of gout?
hyperuricemia