Nucleotides - Purines Flashcards Preview

MCB 2 Block 3 > Nucleotides - Purines > Flashcards

Flashcards in Nucleotides - Purines Deck (21):
1

Basic nucleotide structure

Phosphates with a sugar cx to a base

2

Purines

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

3

Pyrimidines

TCU
Simple, cheap, build base asap, thrown away

4

Purine Synth Ingredients

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

5

Purine Synth Step 1

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)

6

Purine Synth Step 2

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

7

Purine Synth Step 3

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

8

Purine Synth Step 4

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)

9

Purine Synth Step 5

NMP to NTP, ATP always source of Phosphates

10

Purine Synth Step 5 AMP

AMP and P to ADP (1st P) via adenylate kinase
2nd Pi from ETC of substrate lvl phos to ATP

11

Purine Synth Step GMP

GMP and ATP to GDP (via guanylate kinase)
2nd P added (for all non ADP NDPs) via nucleoside diphosphate kinase

12

Regulation of Purine synth

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

13

Purine Recycle GMP

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

14

Purine Recycle AMP

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

15

Purine Degradation

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)

16

Gout

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

17

Lesch Nyan Syndrome

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

18

ADA Def

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

19

PNP Def

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

20

Methotrexate

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

21

Mycophenolic Acid

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