L 42 Purine Nucleotide Biosyn

Question 1

Basic characteristics of bases

Answer 1

purines: 9 memebered bicyclic aromatic rings
- osine
- only one IMP not named by base: hypoxanthine, inosine, inosine monophosphate
- made of SIX components: aspartate, glycine, Amide of two glutamines, THF, CO2. ribose 5 phosphate (from HMP shunt) (all from AA)
- liver is the major site of synthesis, in CYTOSOL (most tissues limited in making purines)

pyrimidines : six membered planar aromatic rings
-idine

Nucleoside: base and sugar
Nucleotide: phophorylated nucleoside
-more negative: usually associated with Mg2+ as counter ion

Question 2

PRPP Synthetase

Answer 2

RL step in puring and py synthesis(found in nearly ALL tissues)

• transfers pyrophosphate to group from ATP to R5P creating PRPP (activated sugar)
• allosterically inhibited by both pur and pu

Question 3

Glutamine PRPP amido transferase

Answer 3

• FIRST COMMITED STEP TO PURING SYNTHESIS
• sequentially adds carbons and nitrogens directly to ribose moiety
• replaces pyrophosphate w/ amide nitrogen of glutaminee releasing glutamate and resulting in a 5PR Amine
• requires glutamine and H2O
• allosterically inhibited by AMP GMP IMP
• allosterically activated by PRPP

Question 4

IMP Inosine Monophosphate Production

Answer 4

1. six ATP required
2. 2 N10F-THF required
   - required for purines and thymidine
   - deficiency in FOLIC ACID results in insufficient nucleotides for normal DNA replication and results in anemia
3. hypoxanthine in IMP is first recognizeable purine
4. 7 of 9 stems to IMP are catalyzed by multifuntional enzymes

-after IMP formed the path splits to either AMP or GMP

Question 5

Starting with IMP going to AMP and GMP, there are two levels of regulation

Answer 5

1. the first committed step in each branch is allosterically regulated via feedback inhibition by its product (GMP and AMP)
2. GTP supplies entegy for AMP syn and ATP supplies energy for GMP synthesis

Question 6

NMP to NDP and NTP

Answer 6

specific nucleoside monophosphate kinases (adenylate kinase, guanylate kinase)

nucleoside DIphosphate kinases: broad specificty and will inter convert most nucleotides to thier triphosphate derivative.

ADP-ATP by ATP synthase in mitochondria (OxPhos)

ATP is present at highest concentration

Question 7

Salvage Pathway: Recycling Nucleic acid breakdown products

Answer 7

extrahepatic tissues!!

APRT

• Adenine to AMP
• require PRPP

and HGPRT(most)

• hypxanthine to IMP
• guanine to GMP
• require PRPP

90% of daily purines come from salvage

salvage requires far less entergy (12 atp compared to 1 ATP)

regualtion:

• decrease in salvage makes more available to stimlate denovo syn
• decrease in salvage decreases nucleotides available to INHIBIT de novo syn.

Question 8

Degradation of purines six steps

Answer 8

1. DNA/RNA or high E compound (ATP/GTP) dephosphorylated to release AMP GMP
2. AMP and GMP converted back to IMP
3. AMP GMP IMP lost phophate group first (forming nucleosides) and thier sugar moeity (free bases)
4. HGPRT is able to recycle from hypoxanthine or guanine and APRT is able to recyle Adenine
5. if not recycled, converted to xanthine
6. XO (Xanthide Oxidase) breaks down in two more steps to Uric Acid (STOP-what is the sig?).

NO ENERY PRODUCTION
-plamsa ammonia levels increase die to AMP degradation

slide 28?

Question 9

balance of purine nucleotides

Answer 9

balance of uric acid produced and denovo purines synthesized change in direct relationship

increase in denovo prod, comparable increase in uric acid prod.