Nucleotides - Purines

Question 1

Basic nucleotide structure

Answer 1

Phosphates with a sugar cx to a base

Question 2

Purines

Answer 2

A and G

Complex, large energy cost, build scaffold then base, recycled if possible

Question 3

Pyrimidines

Answer 3

TCU

Simple, cheap, build base asap, thrown away

Question 4

Purine Synth Ingredients

Answer 4

Asp, Gly, Gln; THF, CO2, Ribose 5P (from HMP), ATP

Question 5

Purine Synth Step 1

Answer 5

Make scaffold
Ribose 5P from HMP shunt turned to phosphoribosyl 1 pyrophosphate (PRPP)
Enz = PRPP synthase
Rqrs=ATP to AMP
Inhib by downstream products (IMP, AMP, GMP)

Question 6

Purine Synth Step 2

Answer 6

Start on Base
PRPP loses pyrophosphate (PP) and gets animated by Gln
Enz = glutamine phosphoribosyl amidotransferase
Allo reg: + by PRPP - downstream

Question 7

Purine Synth Step 3

Answer 7

Make IMP
Add all ingredients, Gly serves as backbone of base
THF, Gln, CO2, Asp, ATP
Makes Inosine monophosphate (IMP)

Question 8

Purine Synth Step 4

Answer 8

Destinations
AMP: rqrs GTP and Asp and fumurate is released
GMP: IMP to XMP (via IMP dehydrogenase, rqrs NAD) to GMP (via GMP synthase, rqrs ATP and Gln; glutamate is released)

Question 9

Purine Synth Step 5

Answer 9

NMP to NTP, ATP always source of Phosphates

Question 10

Purine Synth Step 5 AMP

Answer 10

AMP and P to ADP (1st P) via adenylate kinase

2nd Pi from ETC of substrate lvl phos to ATP

Question 11

Purine Synth Step GMP

Answer 11

GMP and ATP to GDP (via guanylate kinase)

2nd P added (for all non ADP NDPs) via nucleoside diphosphate kinase

Question 12

Regulation of Purine synth

Answer 12

Dependent on bodies need

In enough of both, purine synth stops and nay left over PRPP used for Pyr

Question 13

Purine Recycle GMP

Answer 13

Each purine costs 20 ATP, GMP converted to guanosine by removal of P. Ribose removed via purine nucleoside phosphorylase (PNP) converting it to guanine
HGPRT used to add PRPP to guanine to remake GMP

Question 14

Purine Recycle AMP

Answer 14

AMP to adenosine by removal of P. Adenosine is deanminated using adenosine deaminase (ADA) converting it to Inosine. Inosine uses PNP to remove ribose converting it to hypoxanthine
Hypoxanthine is recycle to IMP using HGPRT. IMP used to remake AMP

Question 15

Purine Degradation

Answer 15

Guanine also converted to Xanthine
Hypoxanthing (AMP) to Xanthine (via xanthine oxidase; rqrs Mo)
Xanthine converted to uric acid/urate (via xanthine oxidase; rqrs Mo)

Question 16

Gout

Answer 16

Too much uric acid/urate leads to crystallization in periph joins
Treatment is allopurinol which comp inhibs xanthine oxidase

Question 17

Lesch Nyan Syndrome

Answer 17

Lethal
Mut in HGPRT, x linked, young leads to increased PRPP and decreased IMP and GMP
This leads to increased purine synth and therefore increased uric acid
Presents as gout and aggression

Question 18

ADA Def

Answer 18

SCID
Mut in ADA leads to increased adenosine which inhib ribonucleoside reductase (needed for DNA synth) leading to deficit in lymphocytes (B,T, NK)
Treatment is enzyme replacement therapy

Question 19

PNP Def

Answer 19

SCID
Mut in PNP, prevents recycling of GMP and IMP
Only T cells affected

Question 20

Methotrexate

Answer 20

Folic Acid analog
Inhibits dihydrofolate reductase, preventing TH2 to THF, limits amount of THF available for purine synth therefore slows DNA synth. Useful with chemo

Question 21

Mycophenolic Acid

Answer 21

Reversible uncomp inhib of IMP dehydrogenase therefore preventing buildup of GMP
Deprives T and B cells so used in graft rejections