M1-C1-L67 --> Nucleotide Metabolism
Terms
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- What are the activated precursors of DNA and RNA synthesis? x 2
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1. NTP
2. dNTP - ATP is made from what?
- Sugar
- How do NTP's regulate protein function? x 2
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1. Through phosophorylation
2. Binding and hydrolysis - A nitrogenous base + sugar = ?
- Nucleoside
- A nitrogenous base + sugar + phosphates = ?
- Nucleotide
- Name all the nitrogenous bases.
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1. Adenosine
2. Cytosine
3. Guanine
4. Thymine
5. Uracil - Name all the nucleosides.
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1. Adenosine
2. Cytidine
3. Guanosine
4. Uridine - Name all the deoxy nucleosides.
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1. Deoxyadenosine
2. Deoxycytidine
3. Deoxyguanosine
4. Deoxythymidine
5. Deoxyuridine - Name all the nucleotides.
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1. Adenylate
2. Cytidylate
3. Guanylate
4. Uridylate - Name all the deoxy nucleotides.
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1. Deoxyadenylate
2. Deoxycytidylate
3. Deoxyguanylate
4. Deoxythymidylate
5. Deoxyuridylate - What are the derived components from which Purine ring is made from? 5
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1. Formate
2. Glutamine
3. Glycine
4. Carbon Dioxide
5. Aspartate - What is the first step in purine synthesis?
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Ribose 5 Phosphate + ATP --> PRPP.
Enzyme - PRPP synthetase - What is the first COMMITTED step in purine synthesis?
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PRPP + glutamine --> Phosphoribosylamine
Enzyme - Glutamine-PRPP amidotransferase - What is the first purine made in purine biosynthesis?
- Inosine
- What is the base of inosinate (IMP)?
- hypoxanthine
- IMP with the addition of ATP becomes what?
- GMP
- IMP with the addition of GTP becomes what?
- AMP
- What is the precursor for AMP and GMP?
- IMP
- If ATP is higher than GTP, more IMP will be converted to what?
- GMP
- If GTP is higher than ATP, more IMP will be converted to what?
- AMP
- What are the inhibitors of PRPP synthetase?
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IMP
AMP
GMP - What are the inhibitors of Glutamine-PRPP amidotransferase?
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IMP
AMP
GMP - What are the inhibitors of adenylosuccinate synthetase?
- AMP
- What are the inhibitors of IMP dehydrogenase?
- GMP
- The pyrimidine ring is made from what components?
- Carbamoyl phosphate and Aspartate
- What is the first step of pyrimidine synthesis?
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Glutamine + 2 ATP + HCO3- --> Carbamoyl Phosphate
Enzyme - Carbamoyl Synthetase II - Carbamoyl synthetase II is found where?
- Cytosol
- What is the first COMMITTED step in pyrimidine synthesis?
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Carbamoyl Phosphate + Aspartate --> N-Carbamoylaspartate
Enzyme - Aspartate transcarbamoylase - What does the enzyme dihydroorotase do?
- Ring closure of pyrimidine
- What is CAD?
- Trimer enzyme containing Carbamoyl synthetase, Aspartate Transcarbamoylase, and Dihydroorotate.
- What is dihydrooroate?
- Closed off ring of pyrimidine synthesis
- What part of pyrimidine synthesis occurs in the mitochondria?
- Dihydroorotate diffuses into mitochondria where it is oxidized by dihydroorotate dehydrogenase to become orotate.
- What happens first to orotate in the cytosol?
- In the presnece of PRPP, becomes subject to orotate-phosphoribosyl transferase, to become orotidylate.
- What happens to orotidylate?
- Becomes subject to orotidylate decarboxylase to become UMP (Uridylate)
- What is unique about the enzymes orotate phosphoribosyl transferase and orotidylate decarboxylase?
- On the same enzyme
- What is the disorder associated with the defect in Orotate Phosphoribosyl Transferase AND Orotidyl Decarboxylase?
- Oroticaciduria type I
- What is the disorder associated with the defect in Orotidylate Decarboxylase?
- Oroticaciduria type II
- What are the markers for patients with oroticaciduria?
- Anemia and high levels of orotate.
- Uridylate (UMP) becomes UTP how?
- Kinases
- UTP becomes CTP (Cytidine) how?
- Addition of glutamine under the subjection of cytidylate synthetase.
- In animals, what are the activators of Carbamoyl Synthetase II?
- PRPP and ATP
- In animals, what are the inhibitors of Carbamoyl Synthetase II?
- UTP and CTP
- In animals, what is the enzyme that needs to be regulated in pyrimidine synthesis?
- Carbamoyl Synthetase II
- In bacteria, what is the enzyme that needs to be regulated in pyrimidine synthesis?
- Aspartate Transcarbamoylase
- What is the reasoning behind the rare incidence where the first committed step is not the regulated step?
- Because carbamoyl phosphate is also made in the urea cycle.
- Why do some Urea cycle disorders increase orotate levels.
- B/c carbamoyl phosphate is common to both urea cycle and pyrimidine synthesis. A urea cycle disorder will lead to carbamoyl phosphate diffusing out of the mitochondria, leading to increased pyrimidine synthesis.
- What pathways are involved in carbamoyl synthetase?
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Carbamoyl synthetase I - Urea cycle
Carbamoyl synthetase II - Pyrimidine synthesis - Where would you find the carbomoyl synthetases?
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Carbamoyl Synthetase I - in mitochondria
Carbamoyl Synthetase II - in cytosol - What do the Carbamoyl Synthetases use?
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Carbamoyl Synthetase I - uses NH4 + HCO3-
Carbamoyl Synthetase II - uses glutamine and HCO3-