Nucleotide synthesis and metabolism Flashcards Preview

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Flashcards in Nucleotide synthesis and metabolism Deck (20)
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1
Q

Where does purine synthesis occur

A

Liver

2
Q

Are purines assembled and then ribosylated, or synthesized onto an existing ribose?

A

Purines are synthesized onto an already phophorylated ribose-5-phosphate.

3
Q

What substrates are needed for purine synthesis

A
Ribose-5-phosphate, 
glycine
glutamine
CO2
Aspartate
N10-Formyl-THF
6ATP
4
Q

What is the initial purine synthesized

A

Inosine-monophosphate IMP.

5
Q

What is the salvage pathway for purines?

A

Purine BASES with no attached ribose are salvaged.

APRT, Adenine PhosphoRibosyl Transferase
and
HPRT, Hypoxanthine-guanine PhosphoRibosyl Transferase

HPRT deficiency results in Lesch-Nyan syndrome. Elevated PRPP, Uricemia,
Decreased IMP and GMP,

6
Q

What is PRPP

pyro-

A

Phospho-Ribosyl-PyroPhosphate

This is the substrate used to add Ribose-phosphate to a Purine base.

7
Q

What enzyme and co-factor is used to reduce Ribonucleotides to Deoxyribonucleotides

A

Ribonucleotide diphosphate reductase, and Thioredoxin cofactor, plus an ATP allosteric activator.

Thioredoxin reductase plus NADPH is then needed to reduce the oxidized thioredoxin back to useable reduced state.

8
Q

What are the products of purine metabolism (degradation)

A

Adenosine –> Inosine –> Hypoxanthine –> Uric acid

Guanosine –> Xanthine –> Uric acid.

9
Q

What is the first enzyme of Pyrimidine synthesis

A

Carbamoyl Phosphate Synthetase 2. CPT II.

CO2 + Glutamine + 2ATP –> Carbamoyl phosphate + 2 ADP + Pi

10
Q

What are the differences between CPT 1 and CPT2

A

Both are in the kidney.

Substrates
CPT1: HCO3- NH3 and ATP. Bicarbonate, Amonia and ATP

CPT2: CO2 + Glutamine + 2 ATP –> Carbamoyl Phos + 2ADP + Pi

11
Q

What is the first enzyme of Purine synthesis (de novo)

A

1) PRPP synthetase
Ribose-5-phosphate + ATP => PRPP + AMP

2) Glutamine:PRPP amidotransferase
PRPP + Glutamine => 5-phsophoribosylamine + glutamate

12
Q

What are the substrates needed for Pyrimidine de novo synthesis

A

Asparate, Glutamine, CO2, 4 ATP, and PRPP.

13
Q

What is the first pyrimidine synthesized in the de novo pathway

A

Orotidine 5 monophosphate, OMP

14
Q

What enzyme contains the CPT 2 catalytic domain?

A
CAD.
It contains:
CPT2
Aspartate transcarbamoylase
Dihydroorotase

Catalyzes:
CO + Glutamine + 2ATP + Aspartate -> -> -> Dihydro Orotate

15
Q

What enzyme follows CAD?

A
UMP Synthetase:
Contains 2 domains:
Orotate phosphoribosyl transferase
and 
OMP decarboxylase
16
Q

Are pyrimidines synthesized onto and existing Ribosyl-phosphate or are they synthesized first and then phospho-ribosylated?

A

The pyrimidines are synthesized and the then ribose-phosphate is added.

17
Q

What cofactor is used to methylate dUMP to generate dTMP

A

The thymidylate synthetase enzyme uses the THF tetrahydrofolate cofactor.

18
Q

Pyrimidine salvage

A

Does not occur to a large degree, because during degradation, the pyrimidine rings are cleaved to beta-alanine (from CMP and UMP) and beta-aminoisobutyrate (from TMP).

Pyrimidine bases can be salvaged by uracil phosphorylase or pyrimidine nucleoside phosphorylase, which adds ribose-1-phosphate. Then uridine/cytidine/tyhmidine kinase removes the 1 phos and adds 5 phos.

19
Q

Deoxynucleoside salvage

A

deoxycytidine kinase. Salvages base-riboses, by phosphorylating them.
Salvages deoxy- Adeonsine, deoxy-Guanosine, AND deoxy-Cytidine

Targeted in leukemias because it is lymphoid specific.

20
Q

Thymidine kinase

A

Very specific to salvage Thymidine (deoxyribose-thymine

Expressed only during active S-phase of cells.

Gancyclovir/Acyclovir are antibiotics which target this enzyme to kill rapidly dividing cells.