Pyrimidines and purines

adenine

thymine

cytosine

guanine

uracil

PRPP is made from

ribose 5-phosphate

What enzyme makes PRPP?

PRPP synthetase

Pyrimidibe synthesis proceeds by first making the pyrimidine ring in the form of

orotate

OMP/ortidylate

Where is CPS-II located

cytosol

What does CPS-II do?

it makes carbamoyl phosphate using glutamine, CO2, and ATP

CPS-II is dependent on

glutamine

CPS-II has an _______________ to prevent protonation of ammonia

ammonia tunnel

There are ___ carbamoyl pools located in

2; mitochondria; cytosol

A UCD could lead to the leakage of carbamoyl phosphate, leading to

orotic aciduria

Aspartate transcarbomoylase catalyzes

aspartate —> carbamoylaspartate

dihydroorotase

carbamoylaspartate —> dihydroorotate

dihydroorotate dehydrogenase (DHODH)

dihydroorotate —> orotate

orotate phosphoribosyltransferase

orotate—> OMP/ortidylate

orotic acid/orotate

ortidylate decarboxylase

orotidylate —> uritidylate UMP

UMP/uritidylate

kinases

UMP—> UTP (uridine 5’-triphosphate)

cytidylate synthetase (CS-II)

UTP—>CTP

UTP

CTP

thymidylate synthase

dUMP—> dTMP

dihydrofolate reductase

dihydrofolate—> tetrahydrofolate

CAD complex

• CPSII

• ATCase

• DHODH

CPSII is inhibited by

UTP

CPSII is activated by

PRPP

Aspartate transcarbamoylase (ATCase) is inhibited by

CTP

ATCase is activated by

ATP

CSII is activated by

GTP

prymidine degradation lead to NH4 production and

urea cycle

Carbons of thymine are degraded to

succinyl CoA

carbons of cytosine and uracil get degraded to

Acetyl CoA

first step of purine synthesis

PRPP—> 5-phospho-B-D-ribosylamine

what AA acts as an amine group donor in the first stage of purine synthesis

glutamine

second step of purine synthesis

5-phospho-B-D-ribosylamine (and glycine)—→ GAR (glycinamide ribonucleotide)

IMP/inosinate

last step of purine synthesis

FAICAR—> IMP

the first step of purine synthesis is catalyzed by

glutamine-PRPP amidotransferase

the last step of purine synthesis is catalyzed by

IMP synthase

adenylosuccinate

AMP

XMP

GMP

nucleoside monophosphate kinases

use ATP to form other nucleoside diphosphates

nucleoside diphosphate kinases

convert nucleoside diphosphates to triphosphates

inhibitors of PRPP synthetase

ADP

inhibitors of glutamine PRPP amidotransferase

AMP,GMP, IMP

inhibitor of adenylosuccinate

AMP (stops making more AMP)

inhibitor of IMP dehydrogenase

GMP (stops making more GMP)

HGPRT

catalyzes the salvage of guanine and xanthine

adenosine phosphoribosyl-transferase

catalyzes the reaction of a free adenine with PRPP to make AMP

ribonucleotide reductase

ribo—> deoxyribo

thioredoxin

intermediate hydrogen carrying protein

glutaredoxin

transfers reduxing power from GSH to ribonucleotide reductase

thioredoxin reductase

catalyzes the reduction of the oxidized form of thioredoxin

5’ nucleotidase

GMP/AMP to guanosine/adenosine

nucleosidase

guanosine/inosine to guanine/hypoxanthine

guanine deaminase

guanine to xanthine

adenosine deaminase

adenosine to inosine

xanthine oxidase

hypoxanthine to xanthine

ALSO

xanthine to uric acid

biotin

transfers CO2

tetrahydrofolate

transfers oxidation states

SAM

transfers methyl groups