PURINE METABOLISM Flashcards
(19 cards)
THREE TYPES OF PURINE METABOLISM
SYNTHESIS
SALVAGE
BREAKDOWN
WHAT ARE THE SOURCES OF PURINE?
DIET (EXOGENOUS)
BYOCHEMICAL SYNTHESIS (ENDOGENOUS)
-DIRECT SYNTHESIS
-SALVAGE
WHAT IS THE GOAL IN PURINE SYNTHESIS
THE GOAL IS CREATE AMP AND GMP
WHAT IS THE INGREDIENTS FOR TO FORM PURINES
-RIBOSE PHOSPHATE
-AMINOACIDS : ASPARTATE, GLYCINE AND GLUTAMINE
-CARBONS ( TETRAHYDROFOLATES, CO2)
WHAT IS THE STEP 1 IN THE SYNTHESIS OF PURINES
STEP 1: CREATE PRPP - 5-PHOSPHORYBOSIL -1-PYROPHOSPHATE
WHAT IS THE STEP 2 IN THE SYNTHESIS OF PURINES
CREATE IMP - IONISE MONOPHOSPHATE , HAS A BASE CALLED HYPOXANTHINE
HOW A PURINE IS FORMED
ALL PURINES HAVE TWO NITROGEN GROUPS IN EACH RING
- 6 UNIT, 3 DOUBLE BONDS
- 5 UNIT, 2 DOUBLE BONDS
WHAT IS THE STEP 3 IN THE SYNTHESIS OF PURINES
CREATES AMP AND GMP
HOW PURINES SYNTHESIS BEGINS
STARTS WITH RIBOSE PHOSPHATE FROM HMP SHUNT
WHAT IS THE ROLE OF RIBAVIRIN?
RIBAVIRIN IS ANTIVIRAL
-Inhibits IMP dehydrogenase
-Blocks conversion IMP to GMP
- Inhibits synthesis guanine nucleotides (purines)
WHAT IS THE ROLE OF MYCOPHENOLATE
Mycophenolate (immunosuppressant)
Inhibits IMP dehydrogenase
PURINE FATES
URIC ACID
XPLAIN ABOUT PURINE SALVAGE
IS AN ALTERNATIVE WAY TO FORM PURINE NUCLEOTIDES BY RECYCLING PRE-EXISTING BASES.
THIS PATHWAY SALVAGES THE BASES ADENINE, GUANINE AND HYPOXANTHINECONVERT THEM BACK INTO THEIR RESPECTIVE NUCLEOTIDES AMP, GMP, AND IMP. THIS PROCESS ALSO REQUIRES PRPP.
XPLAIN THE MOLECULAR PROCESS ABOUT PURINE SALVAGE
HYPOXANTHINE AND GUANINE CONVERTS INTO IMP AND GMP RESPECTLY, FOR HGPRT.
KEY: HGPRT (HYPOXANTHINE - GUANINE PHOSPHORIBOSYL TRANSFERASE)
ADENINE CONVERT INTO AMP FOR APRT
APRT: ADENINE PHOSPHORIBOSYLTRANSFERASE)
WHAT IS THE ROLE OF 6-MERCAPTOPURINE
Chemotherapy agent
Mimics hypoxanthine/guanine
Added to PRPP by HGPRT –> Thioinosinic acid
Inhibits multiple steps in de novo synthesis
↓IMP/AMP/GMP
WHAT IS THE ROLE AZATHIOPRINE
IS CONVERTED IN THE BODY INTO 6-MP
Immunosuppressant.
Metabolized by xanthine oxidase
Caution with allopurinol, May boost effects, May increase toxicity
WHAT IS THE PROCESS PURINE BREAKDOWN
GUANINE ( GUANASE ENZYME ) –> XANTHINE
HYPOXANTHINE ( XANTHINE OXIDASE ENZYME ) –> XANTHINE
XANTHINE ( XANTHINE OXIDASE )–> URIC ACID
XPLAIN ABOUT THE GOUT
GOUT WHICH IS CAUSED BY EXCESS URIC ACID LEADING CRYSTAL DEPOSITION IN JOINTS, RESULTING IN PAIN, SWELLING AND REDNESS.
GOUT CAN OCCUR DUE TO THE OVERPRODUCTION OF URIC ACID (FROM HIGH CELL TURN OVER LIKE TRAUMA OR CHEMOTHERAPY) OR FROM CONSUMING PURINE RICH FOODS, LIKE MEAT AND SEA FOOD. A COMMON TREATMENT FOR GOUT IS TO INHIBIT XANTHINE OXIDASE USING ALLOPURINOL.
XPLAIN LESCH-NYHAN SYNDROME
EXCESS URIC ACID, PRODUCTION BEACUSE THE LACK OF HGPRT PUSHES MORE PRECURSORS TOWARDS THE BREAKDOWN PATHWAY.
-deficiency of the HPRT enzyme
-Excess de novo purine synthesis (
(↑PRPP, ↑IMP)
Hypotonia, chorea
Classic feature: self mutilating behavior (biting, scratching)
No treatment
Classic presentation
Male child with motor symptoms, self
mutilation, gout
