Nucleotide Metabolism

Question 1

What is the difference between purines and pyrimidines?

Answer 1

Pyrimidines- big name, smaller (1) ring

Purines- small name, bigger (2) rings

Question 2

What is a nucleoside? Nucleotide?

Answer 2

Sugar + base

Sugar+ base+ phosphate(s)

Question 3

What is the role of nucleotide sugars in the body?

They act as activated monosaccharide donors
They are used in glycogen synthesis
They are used in glycoprotein synthesis
They are used in glycolipid synthesis
All of the above

Answer 3

All of the above

Question 4

Where are purines synthesized? Where are they salvaged?

Answer 4

Synthesized in the liver and cytosol

Salvaged in organelles

Question 5

Where are pyrimidines synthesized? Where are they salvaged?

Answer 5

Synthesized in the liver, cytosol, and mitochondria

Salvaged in the organelles

Question 6

What are the 3 atomic sources for pyrimidine bases?

Answer 6

Glutamine amide
Aspartate
Bicarbonate

Question 7

What are the 5 atomic sources for purine bases?

Answer 7

Glutamine amide
Aspartate amine
Bicarbonate

Glycine
Formate

Question 8

Describe the quick version of the synthesis of purines.

Answer 8

First the ribose-5-phosphate base is formed from the pentose phosphate pathway. Then this is added to the purine nucleotide.

Question 9

Describe the quick version of the synthesis of pyrimidines.

Answer 9

First the pyrimidine nucleotide is formed, followed by the addition of ribose phosphate.

Question 10

List the 4 phases of purine synthesis.

Answer 10

Phase I: activation of ribose-5-phosphate
Phase II: conversion of PRPP into phosphoribosylamine *Committed step
Phase III: construction of IMP (branch point during purine synthesis)
Phase IV: conversion of IMP into either Adenosine and Guanosine, and then their deoxy constituents

Question 11

During purine synthesis, for phase I (activation of ribose-5-phosphate, where does ribose-5-phosphate come from?What activates phase I and what inhibits it?

Answer 11

The pentose phosphate pathway

Activated by inorganic phosphate due to ATP consumption

Inhibited by levels of purine nucleotides GMP, AMP, and IMP

Question 12

During purine synthesis, for phase II (conversion of PRPP into phosphoribosylamine) why is this step important? What allosterically activates and inhibits this step?

Answer 12

This is important because it is the committed step.

It is activated by PRPP

It is inhibited by levels of purine nucleotides GMP. AMP, and IMP

Question 13

During purine synthesis, for phase III (construction of IMP) what inhibits this phase? What is this inhibitor used for?

Answer 13

Methotrexate

Used to treat cancers because IMP is the branch point for purine synthesis. If you inhibit this you cannot make adenine or guanine.

It also prevents the oxidation of NADPH.

Question 14

What are the two regulation pathways for purine synthesis?

Answer 14

Inhibited by feedback and cross regulation

Feedback from PRPP, Phosphoribosyl amine, and AMP/GMP from IMP

Cross Regulation:
AMP synthesis is stimulated by GTP
GMP synthesis is stimulated by ATP

Question 15

What are the 3 phases of pyrimidine synthesis?

Answer 15

Phase I: fabrication of pyrimidine as orotate *Rate limiting
Phase II: attaching orotate to PRPP to form UMP (the branch point of pyrimidine synthesis)
Phase III: converting UMP into cytosine and thymidine and then their deoxy constituents

Question 16

Describe phase I of pyrimidine synthesis. What enzyme is first used and what compound is ultimately made?

Answer 16

Glutamine is converted into Aspartate transcarbamoylase via carbamoyl phosphate synthetase II. Asp transcarbamoylase is ultimately converted into orotate.

Question 17

What stimulates and what inhibits carbamoyl phosphate synthetase II and Asp transcarbamoylase during phase I of pyrimidine synthesis?

Answer 17

CPS II:
Inhibited by UMP/UTP
Stimulated by PRPP

Asp Transcarbamoylase:
Inhibited by CTP

Question 18

During phase III of the pyrimidine synthesis, describe why dUDP has to go through this loop in order to form dTTP/

Answer 18

The reason is to keep dUTP in low amounts so as not to incorporate any uracil into DNA.

*Note that dUMP is the bridge to thymine production here

Question 19

What organ in humans is the principle site of purine and pyrimidine synthesis? What molecule is utilized?

Answer 19

Liver

ribose-5-phosphate

Question 20

Why are sulfa drugs important?

Answer 20

They selectively disrupt DNA replication in bacteria

Question 21

What are 2 compounds the pentose phosphate pathway produces?

Answer 21

Ribose-5-phosphate

NADPH

Question 22

Describe how Acyclovir is an antiviral agent.

Answer 22

Acyclo-dGTP (pseudo dGTP) is incorporated into rapidly dividing cells and terminates DNA replication because it lacks a 3’-OH group

Question 23

What is the main molecule that builds up in patients that are suffering from gout? What medicine is used to treat this?

Answer 23

Uric Acid

Allopurinol

Question 24

Describe the biochemical background on what occurs during patients that are suffering from SCID.

Answer 24

These patients have an increase in dATP, which inhibits ribonucleitide reductases which in turn blocks the formation of all the other dNDPs.

Low levels of dNDP and dNTP impairs DNA synthesis and leads to a compromised immune system.

Question 25

What is the treatment for controlling gout?

Answer 25

To control your purine intake. Uric acid is formed from having a high purine diet (beans, spinach, lentils) along with alcohol, meat, and seafood. All of these increase the soluble purines hypoxanthines and guanine, which are used to form uric acid.

Question 26

What enzyme is deficient in the purine salvage pathway that leads to Lesch-Nehan Syndrome?

Answer 26

Hypoxanthing-guanine Phosphoribosyltransferase (HGPRT), which is used to generate GMP or IMP Note that this is the disease that causes you to bite things uncontrollably (self mutilation) if you have a deficiency in GMP or IMP