Which of the following is not true about hypoxanthineguanine phosphoribosyl transferase?
a. Predominantly present in liverb. Involved in purine metabolism
c. PRPP is the substrate required
d. Its deficiency leads to Lysch Nyhan disease.
Ans.
C.
“SALVAGE REACTIONS” CONVERT PURINES & THEIR NUCLEOSIDES TO MONONUCLEOTIDES
Conversion of purines, their ribonucleosides, and their deoxyribonuc]eosides to mononucleotides involves so- called “salvage reactions” that require far less energy than de novo synthesis. The more important mechanism involves phosphoribosylation by PRPP of a free punine (Pu) to form a purine 5’-mononucleotide (Pu-RP).
Three processes contribute to purine nucleotide biosynthesis. These are, in order of decreasing importance:
(1) Synthesis from amphibolic intermediates (synthesis de novo),
(2) Phosphoribosyltion of purines, and
(3) Phosphorylation of purine nucleosides.
Lesch-Nyhan Syndrome
• X-linked recessive.
• Overproduction hyperuricemia.
• Purine salvage problem owing to absence of HGPRT, which converts hypoxanthine to IMP and guanine to GMP.
• C/f:
o Mental retardation,
o Self-mutilation, aggression,
o Hyperuricemia, gout, and
o Choreoathetosis.
• Reflects a defect in hypoxanthine-guanine phosphoribosyl transferase (HGPRTase), an enzyme of purine salvage.
• The accompanying rise in intracellular PRPP results in purine overproduction.
• Mutations that decrease or abolish hypoxanthine-guanine phosphoribosyl transferase activity include deletions, frame-shift mutations, base substitutions, and aberrant mRNA splicing.
“SALVAGE REACTIONS” CONVERT PURINES & THEIR NUCLEOSIDES TO MONONUCLEOTIDES
Conversion of purines, their ribonucleosides, and their deoxyribonuc]eosides to mononucleotides involves so- called “salvage reactions” that require far less energy than de novo synthesis. The more important mechanism involves phosphoribosylation by PRPP of a free punine (Pu) to form a purine 5’-mononucleotide (Pu-RP).
Three processes contribute to purine nucleotide biosynthesis. These are, in order of decreasing importance:
(1) Synthesis from amphibolic intermediates (synthesis de novo),
(2) Phosphoribosyltion of purines, and
(3) Phosphorylation of purine nucleosides.
Lesch-Nyhan Syndrome
• X-linked recessive.
• Overproduction hyperuricemia.
• Purine salvage problem owing to absence of HGPRT, which converts hypoxanthine to IMP and guanine to GMP.
• C/f:
o Mental retardation,
o Self-mutilation, aggression,
o Hyperuricemia, gout, and
o Choreoathetosis.
• Reflects a defect in hypoxanthine-guanine phosphoribosyl transferase (HGPRTase), an enzyme of purine salvage.
• The accompanying rise in intracellular PRPP results in purine overproduction.
• Mutations that decrease or abolish hypoxanthine-guanine phosphoribosyl transferase activity include deletions, frame-shift mutations, base substitutions, and aberrant mRNA splicing.
