Miles - Nucleotide Metabolism I/II

Question 1

Central Dogma

Answer 1

DNA - transcription - RNA - translation - Protein

Question 2

Are dietary purines/pyrimidines incorporated directly? Injection?

Answer 2

No Yes

Question 3

Mneumonics for Purines vs Pyrimidines Biosynthesis

Answer 3

Purines: PureAsGoldSoundsRight

Purines = Adenosine, Guanine

Synthesis = Sugar then purine Ring

_______________

Pyrimidines: C.U.T. the Pye Really Swift

Pyrimidines = Cytosine, Uracil, Thymine

Synthesis = Ring then Sugar

Question 4

What do the following add in Purin synthesis?

Glutamine

Aspartate

Folic Acid (Formate)

Glycine

Answer 4

Glutamine = + Nitrogen

Aspartate = + Nitrogen

Folic Acid = + Carbon

Glycine = +Carbon/+Nitrogen

Question 5

What are the main regulated steps in Purine synthesis?

What regulates these?

Answer 5

First two steps, catalyzed by:

PRPP: (-) Purine nucleotides (AMP, GMP)

PRPP Glutamyl Amidotransferase:

(+) PRPP

(-) Purine Nucleotides (A,TDM,P/G,TDM,P)

Question 6

What is the first committed step in Purine synthesis?

Answer 6

Step two–Addittion of glutamine to add nitrogen via PRPP Glutamyl Amidotransferase.

Question 7

What occurs after IMP in Purine synthesis and how to these end products regulate the pathway?

Answer 7

Branches to either AMP or GMP, each of which stimulates the other branch

Question 8

What are the main inhibitors of Purine synthesis?

Answer 8

Azaserine (Glutamine Analog) - primarily used in resarch, too toxic to cells

Sulfonamides - block bacterial production of THF (PABA)

Methotrexate - block human production of THF (DHFR)

Question 9

What are key enzymes for Purine salvage?

Answer 9

APRT

HGPRT

Question 10

What diseases can arise from HGPRT deficiency

Answer 10

Lesch-Nyhan Syndrome: HGPRT is lacking or deficient = purine OVERPRODUCTION; will overaccumulate PRPP which feeds forward

Gout: HGPT issue, can treat future outbreaks with Allopurionol

Question 11

Purine Nucleoside Phosphorylase (PNP) Deficiency

Answer 11

No T-Cells

Question 12

Sever Combined Immunodeficiency (SCID)

Answer 12

No B/T Cells - “bubble boy”

Caused by ADA deficiency

Question 13

What are the regulated steps of Pyrimidine synth?

Answer 13

First three steps:

(Main) Carbamoyl Phosphate Synthetase

Aspartate Carbamoylase

Dihydro-orotase

Question 14

What is the committed step in pyrimidine synth?

Answer 14

Second step, conversion of CAP+Asp to CAA by Aspartate Transcarbamoylase

Question 15

What is the role of PRPP in pyrimidine synth?

Answer 15

Adds sugar

Question 16

What regulates the first step of pyrimidine synth?

Answer 16

(+) ATP/PRPP

(-) UTP (end product)

Question 17

Where does pyrimidine synth occur?

Answer 17

Cytosol

Question 18

What is the first compound w/pyrimidine ring in pyrimidine synth?

Answer 18

Orotic Acid (OA)

Question 19

What disease can result in enzyme deficiency in conversion of OA to OMP, or OMP to UMP?

Answer 19

Orotic Aciduria, treat with uridine

Question 20

What is first nucleoTide in pyrimidine synth?

Answer 20

UMP

Question 21

What are two end products of pyrimidine synth?

Answer 21

CTP or TMP

Question 22

What can inhibit pyrimidine synth?

Answer 22

Methotrexate (shut down human production of THF) by block DHFR

5-Gluorocil, shut down production of Methylene H4 Folate by acting as suicide substrate

Question 23

What is the source of the left and right sides of UMP ring?

Answer 23

Left = carbamoyl phosphate (CAP)

Right = Aspartic Acid

Question 24

What enzyme can you block to treat certain viral infections like herpes?

Answer 24

Thymidine Kinase (TK) via Acyclovir in the Pyrimidine Salvage pathways

Question 25

Why do normal cells grow in HAT medium, where Lesch-Nyhan cells die?

Answer 25

Lesch Nyhan cells lack HGPRT, can’t make IMP to make purines

Normal cells have TK and HGPRT

Question 26

What does a deficiency in Adenosine Deaminase (ADA) cause?

What does a deficiency in Purine Nucleoside (PNP) Phosphorylase cause?

Answer 26

SCID (B/T Cell deficiency)

PNP (T Cell deficiency)

Question 27

What does a deficiency in Orotidylate Decarboxylase cause?

Answer 27

Orotic Acidurias