Purines

What makes up a ring atom?

-CO2, Aspartate, Glycine, Formate, Amide of glutamine

-2 ring system is built from PRPP

What are the first two steps of de novo synthesis

1) amino group is donated by glutamine and attached to PRPP to form 5-phosphoribosylamine by glutamine PRPP aminotransferase

2) 3 atoms are added from glycine forming ATP by GAR synthetase to form GAR

In what step is a carbon added in de novo synthesis

Step 3, formate donates 1 carbon

Step 10

In which step does glutamine donate an amine group in de novo synthesis

Step 4, this step also requires ATP

What steps require ATP in de novo synthesis

4, 5, 6, 8, 2

What occurs in step 6 of de novo synthesis

Bicarbonate donates a carbon

What happens in step 8 of de novo synthesis

Aspartate donates an amine group

What occurs in step 11 of de novo synthesis

-Enzyme: IMP Synthase forms IMP

-first purine ring intermediate in pathway

-imidazole ring is converted to imp

What enzymes are involved in conversion of IMP to AMP? What do they use

Adenylosuccinate synthetase: uses Aspartate and GTP

Adenylosuccinate lyase: Releases carbon as fumarate

What enzymes are involved in conversion of IMP to GMP? Whats required/what happens?

IMP Dehydrogenase: Requires NAD+ and makes XMP (Xanthylate monophosphate)

GMP Synthetase: Requires glutamine and ATP to make GMP (Guanylate monophosphate)

Name the structure

AMP (Adenlyate monophosphate)

Name the structure

GMP (Guanylate Mono Phosphate)

What’s the function of nucleoside monophosphate kinases?

use ATP to form other nucleoside

diphosphates

Whats the function of nucleoside diphosphate kinases?

convert nucleoside diphosphates to

triphosphates

What inhibits PRPP Synthetase in Purine synthesis

Inhibitor: AMP

What inhibits Glutamine-PRPP amidotransferase

GMP, AMP, IMP

What inhibits IMP Dehydrogenase (hint: think of what it makes)

GMP

What inhibits adenylosuccinate synthetase

AMP

What’s the point of the purine salvage pathway

Instead of breaking down free bases, they’re recyled into nucleotides. SAVES ENERGY

Function of HGPRT (Purine Salvage Pathway)

uses hypoxanthine/guanine + PRPP > makes IMP or GMP

Function of APRT (Purine Salvage Pathway)

uses adenine and PRPP > makes AMP

Why does ribonucleotide reductase need to be constantly "recharged" by thioredoxin or glutaredoxin?

Because converting ribonucleotides → deoxyribonucleotides oxidizes RNR's active-site cysteines (–SH → –S–S–). It needs electrons donated back to reduce it before it can catalyze another round.

Trace the electron flow from FADH2 to RNR using the thioredoxin pathway

FADH2 → thioredoxin reductase → thioredoxin → RNR (reducing it back to active form)

What's the equivalent electron source for the glutaredoxin pathway?

Glutathione (GSH) — reduced glutathione donates electrons to glutaredoxin, which then reduces RNR.

What’s the process of purine degradation for GMP

1) GMP converted to Guanosine from hydration reaction and loss of phosphate by 5’-nucleotidase

2) Guanosine is converted to Guanine from hydration and loss of ribose by nucleosidase

3) Guanine is converted to xanthine by hydration and removal of NH3 by enzyme guanine deaminase

What’s the process of puring degradation of AMP

1) AMP to Adenoside by 5’nucleotidase

2) Adenosine to Inosine by adenosine deamoninase

3) Inosine to hypoxanthine by nucleosidase

4) Hypoxanthine to xanthine by xanthine oxidase

How is uric acid produced by purine degradation?

Xanthine is to uric acid by xanthine oxidase

name this structure

xanthine

name this structure

xanthine

name this structure

guanine

Cofactors: What is biotins purpose

Transfers CO2

Cofactors: Tetrahydrofolate purpose

transfers intermediate oxidation states

Cofactors: S-adenosylmehtionine

Transfers methyl group