Nucleotide Metabolism 1

Question 1

Where do most of our purines and pyrimidines for nucleotide synthesis?

Answer 1

Synthesized from amphibolic intermediate

Question 2

What is a basic difference between the order of purine and pyrimidine synthesis?

Answer 2

Purine - start with sugar, then build purine ring

Pyrimidine - build the pyrimidine ring, then attach sugar

Question 3

What is the first reaction in purine synthesis?

Answer 3

Ribose-5-phosphate to

Phosphoribosyl pyrophosphate(PRPP)

Enzyme: PRPP Synthase

Question 4

What five molecules are used to build the purine ring?

Answer 4

ATP
Glutamine
Tetrahydrofolate
Aspartate
Glycine

Question 5

What molecule is the branch point for purine synthesis?

Answer 5

Inosine monophosphate (IMP)

Question 6

What is the major site of purine synthesis?

Answer 6

Liver

Question 7

What inhibits PRPP Synthase?

Answer 7

AMP and GMP

Purine nucleotides

Question 8

What is the committed step of De Novo purine synthesis?

Answer 8

PRPP to 5-phosphoribosylamine

Enzyme: glutamine PRPP amidotransferase

(Aka PRPP Glutamyl Amidotransferase)

Question 9

What are the inhibitors of Glutamine PRPP amidotransferase?

Answer 9

ATP, ADP, and AMP at one site

GTP, GDP, and GMP at another

Question 10

What stimulates glutamine PRPP amidotransferase?

Answer 10

PRPP

Question 11

What occurs during the purine synthesis steps involving glutamine?

Answer 11

The addition of a nitrogen group to the ring

Question 12

What occurs during the purine synthesis steps that involve folic acid?

Answer 12

Addition of carbonyl to the purine ring

Question 13

What is the base of IMP?

Answer 13

Hypoxanthine

Question 14

What stimulates the production of AMP?

Answer 14

GTP

Question 15

What stimulates the production of GMP?

Answer 15

ATP

Question 16

What is Azaserine?

Answer 16

Glutamine analog that blocks purine synthesis steps involving glutamine

Primarily used in research.

Question 17

What are sulfonamides and why are they used?

Answer 17

Inhibit folate metabolism in bacteria by competitively inhibiting PABA

Question 18

What is methotrexate and what is its mechanism?

Answer 18

A folate analog that competitively inhibits dihydrofolate reductase

Used in cancer chemotherapy

Question 19

What two disorders are caused by a folic acid deficiency?

Answer 19

Anencephaly

Spinal Bifida

Question 20

Why does folic acid deficiency cause neural tube defects?

Answer 20

Rapidly dividing cells require large amounts of nucleotides, without folic acid can’t keep up with demand, causing delays in neural folding.

Question 21

What reciprocal relationship exists between AMP and GMP formation?

Answer 21

ATP is a substrate for GMP synthesis

GTP is a substrate for AMP synthesis

Question 22

What is purine salvage?

Answer 22

Synthesis of nucleotides from purine bases and nucleosides

Question 23

What two enzymes are involved in the purine salvage pathway?

Answer 23

Adeninephosphoribosyltransferase

APRT

Hypoxanthine-Guanine PhosphoRibosylTransferase

HGPRT

Question 24

What is Lesch-Nyhan Syndrome?

Answer 24

Deficiency or complete lack of HGPRT

Gout and kidney stones

Neurological problems

Self-mutilation

X-linked recessive

Question 25

What is the mechanism for Lesch-Nyhan Syndrome?

Answer 25

Lack of HGPRT causes the build up of PRPP, leading to purine overproduction, and therefore degradation and uric acid build up Brain relies on salvage, so decreased purine production in brain

Question 26

What is the function of purine nucleoside phosphorylase

Answer 26

Removes sugar to yield a free base (hypoxanthine or guanine)

Question 27

What is the final product of purine degradation and what is its biological significance?

Answer 27

Uric Acid Can catch free radicals However, insoluble and can percipitate -kidney stones, gout

Question 28

What causes gout?

Answer 28

Caused by precipitation of urate Result of excess purine production or partial deficiency in HGPRT

Question 29

What is allopurinol and what is used for?

Answer 29

Xanthine analog that blocks xanthine oxidase. This prevents the formation of uric acid and can prevent gout.

Question 30

What is Purine nucleoside phosphorylase deficiency?

Answer 30

Defect in the enzyme Autosomal recessive disorder Causes immunodeficiency - no T cells Rare

Question 31

What is ADA deficiency?

Answer 31

Lack of adenosine deaminase Autosomal recessive Causes Severe combined immunodeficiency (SCID) Destruction of B and T lymphocytes