2. DEGRADATION OF PURINE NUCLEOTIDE
• The end product of purine metabolism in human is URIC ACID
OR URATE
• URIC ACID OR URATE can serve as an important
ANTIOXIDANT
• The normal concentration of URIC ACID in the serum of the
adult is in the range of 3-7mg/dl [males] , 2-5mg/dl [female].
3. STEP 1
THE DEGRADATIOIN BEGIN WITH
EITHER THE DEAMINATION OR
HYDROLYTIC REMOVAL OF
PHOSPHATE GROUP.
THE NUCLEOTIDE MONOPHOSPHATE [ AMP
IMP GMP ] ARE CONVERTED TO THEIR
NUCLEOSIDE FORM [ADENOSINE ,INOSINE
,OR GUANOSINE]
4. STEP 2
ADENOSINE TO HYPOXANTHINE
THE AMINO GROUP , FROM ADENOSINE , CAN
BE REMOVED TO PRODUCE INOSINE .THAN
INOSINE ARE RESPECTIVELY , CONVERTED TO
HYPOXANTHINE BY THE ACTION OF PURINE
NUCLEOSIDE PHOSPHORYLASE
5. STEP 3
HYPOXANTHINE TO XANTHINE ,GMP TO
XANTHINE .
HYPOXANTHINE CONVERT INTO XANTHINE BY THE
ACTON OF XANTHINE OXIDASE
GMP TO GUANOSINE TO GUANINE
THAN GUANINE COVERT INTO XANTHINE
BY THE ACTION OF GUANINE DEAMINASE
6. STEP 4
XANTHINE TO URIC ACID
XANTHINE CONVERT INTO URIC ACID BY
THE ACTION XANTHINE OXIDASE
THAN URIC ACID TO URATE DEPEND
UPON SOLUBILITY OR OTHER FACTORS
9. XANTHINE OXIDASE – A MOLYBDOENZYME
• XANTHINE OXIDASE IS A FORM OF XANTHINE OXIDOREDUCTASE,A TYPE
ENZYME THAT GENERATE REACTIVE OXYGEN SPECIES.
• THESE ENZYME CATALYZE THE OXIDATION OF HYPOXANTHINE TO XANTHINE
AND CAN FURTHUR CATALYZE THE OXIDATION OF XANTHINE TO URIC ACID.
• XANTHINE OXIDASE ,A MOLYBDENUM AND IRON-CONTAINING FLAVOPROTEIN
,HYPOXANTHINE TO XANTHINE AND THAN TO URIC ACID OR URATE
10. SCID [SEVERE COMBINED IMMUNODEFICIENCY]
• A DEFICIENCY IN A ADENOSINE DEAMINASE ACTIVITY IS ASSOCIATED WITH SOME FORM OF SEVERE
COMBINED IMMUNODEFICIENCY [SCID] ,AN IMMUNOLOGICAL DISORDER.
• PERSON WITH THE DISORDER HAVE SEVERE RECURRING INFECTION,OFTEN LEADING TO DEATH AN
EARLY AGE
• SCID IS CHARACTERISED BY A LOSS OF T-CELL ,WHICH ARE CRUCIAL TO THE IMMUNE RESPONSE
• SCID IS OFTEN CALLED THE ‘’BUBBLE BOY DISEASE’’ BECAUSE ITS TREATMENT MAY INCLUDE
COMPLETE ISOLATION OF PATIENT FROM THE ENVIRONMENT ,ADA DEFICIENCY HAS BEEN
SUCESSFULLY TREATED BY GENE THERAPY.
11. GOUT IS INDUCED BY HIGH SERUM LEVEL OF
URATE
• URIC ACID LOSES A PROTON AT PHYSIOLOGICAL pH TO FROM URATE,
• IN HUMAN BEINGS, URATE IS THE FINAL PREODUCT OF PURINE DEGRADATION AND
IS EXCRETED IN THE URINE.
• HIGH SERUM LEVELS OF URATE( HYPERURICEMIA) INDUCE THE PAINFUL JOINT
DISEASE GOUT.
• IN THIS DISEASE THE SODIUM SALT OF UREATE CRYSTALIZE IN THE FLUID AND
LINING OF THE JOINTS.
• PAINFUL INLAMATION RESULT WHEN CELL OF IMMUNE SYSTEM INGULF THE SODUM
UREATE CRYSTALS.
12.
13. TREATMENT OF GOUT
• ADMINISTARTION OF ALLOPURINOL, AN ANALOG OF HYPOXANTHINE IS ONE
TREATMENT OF GOUT.
• ALLOPURINOL ACTS AS BOTH AS SUSBSTRATE AND AS INHIBITOR OF XANTHINE
OXIDASE.
• THE SYNTHESIS OF UREATE FROM HYPOXANTHINE AND XANTHINE DECREASES
SOON AFTER THE ADMINISTARTION OF ALLOPURINOL. THE SERUM
CONCENTRATRION OF HYPOXANTHINE AND XANTHINE RISE, AND THAT OF
URATE DROPS.
14. LESCH-NYHAN SYNDROME
• MUTATION IN GENES THAT INCODE NUCLEOTIDE BIOSYNTHETIC ENZYMES CAN
REDUCE LEVEL OF NEEDED NUCLEOTIDE AND CAN LEAD TO THE ACCUMULATION OF
INTERMEDIATES.
• A NEARLY TOTAL ABSENCE OF HYPOXANTHINE-GUANINE PHOSPHORIBOSYL
TRANSFERASE HAS UNEXPECTED AND DEVASTATING CONSEQUENCES
• THE MOST STRIKING EXPRESSION OF THIS INBORN ERROR OF METABOLISM CALLED
LESCH-NYHAN SYNDROME, IS A COMPULSIVE SELF DESTRUCTIVE BEHAVIOUR.
• MENTAL DEFICIENCY AND SPASTICITY ARE OTHER CHARACTERSTICS OF LESCH-
NYHAN SYNDROME.