BACHELOR OF SCIENCE IN NURSING (BSN)
B.SC NURSING
Nucleic Acid Metabolism
1. Describe the sources of carbon and nitrogen atoms of purine nucleotide. Write the path-
way for de novo purine synthesis. Add a note on its regulation and inhibitors.
Definition: Purine synthesis involves sequential addition of carbon and nitrogen atoms
to ribose 5’-phosphate to generate nine-membered ring (Fig. 14.1). Sources of carbon and
nitrogen atoms of purine nucleotide are given in the Table 14.1.
Site: Liver.
Subcellular site: Cytosol.
Starting material: Ribose 5’-phosphate.
End product: Inosine monophosphate (IMP).
Sources of different atoms of purine ring
Atoms Sources
N1 Aspartate
C 2, C 8 N10 tetrahydrofolate
N 3, N 9 Glutamine
C 4, C 5, N 7 Glycine
C6 CO2
Ch-14.indd 181 21-06-2014 11:51:43
, 381
Regulators and inhibitors of purine synthesis are explained in Tables 14.2 and 14.3
respectively.
Regulation of purine synthesis
Enzyme Inhibitor
Stimulator PRPP* synthetase AMP‡, GMP§ –
Amidotransferase GMP, AMP –
Adenylosuccinate synthetase AMP GTP||
IMP† dehydrogenase GMP –
PRPP, phosphoribosyl pyrophosphate; †IMP, inosine monophosphate; ‡AMP, adenosine monophosphate; §GMP, guanosine mono-
*
phosphate; ||GTP, guanosine triphosphate.
Nucleic Acid Metabolism
Inhibitors of purine synthesis
Inhibitor Mechanism of action
Sulfonamides PABA* analogues block folate synthesis in microbes
6-mercaptopurine Inhibits formation of AMP and GMP from IMP
Mycophenolic acid Inhibits IMP† dehydrogenase (used to prevent graft rejection)
Methotrexate Inhibits dihydrofolate reductase, reduces availability of active folate
and blocks purine synthesis; it is used as an anticancer agent
*
PABA, para-aminobenzoic acid; †IMP, inosine monophosphate.
2. How are purine bases salvaged? Add a note on Lesch-Nyhan syndrome.
Definition: It involves conversion of purines, purine ribonucleosides and purine deoxy
ribonucleosides to corresponding mononucleotides.
Reactions:
i. Phosphoribosylation of free purines.
Ch-14.indd 183 21-06-2014 11:51:44
B.SC NURSING
Nucleic Acid Metabolism
1. Describe the sources of carbon and nitrogen atoms of purine nucleotide. Write the path-
way for de novo purine synthesis. Add a note on its regulation and inhibitors.
Definition: Purine synthesis involves sequential addition of carbon and nitrogen atoms
to ribose 5’-phosphate to generate nine-membered ring (Fig. 14.1). Sources of carbon and
nitrogen atoms of purine nucleotide are given in the Table 14.1.
Site: Liver.
Subcellular site: Cytosol.
Starting material: Ribose 5’-phosphate.
End product: Inosine monophosphate (IMP).
Sources of different atoms of purine ring
Atoms Sources
N1 Aspartate
C 2, C 8 N10 tetrahydrofolate
N 3, N 9 Glutamine
C 4, C 5, N 7 Glycine
C6 CO2
Ch-14.indd 181 21-06-2014 11:51:43
, 381
Regulators and inhibitors of purine synthesis are explained in Tables 14.2 and 14.3
respectively.
Regulation of purine synthesis
Enzyme Inhibitor
Stimulator PRPP* synthetase AMP‡, GMP§ –
Amidotransferase GMP, AMP –
Adenylosuccinate synthetase AMP GTP||
IMP† dehydrogenase GMP –
PRPP, phosphoribosyl pyrophosphate; †IMP, inosine monophosphate; ‡AMP, adenosine monophosphate; §GMP, guanosine mono-
*
phosphate; ||GTP, guanosine triphosphate.
Nucleic Acid Metabolism
Inhibitors of purine synthesis
Inhibitor Mechanism of action
Sulfonamides PABA* analogues block folate synthesis in microbes
6-mercaptopurine Inhibits formation of AMP and GMP from IMP
Mycophenolic acid Inhibits IMP† dehydrogenase (used to prevent graft rejection)
Methotrexate Inhibits dihydrofolate reductase, reduces availability of active folate
and blocks purine synthesis; it is used as an anticancer agent
*
PABA, para-aminobenzoic acid; †IMP, inosine monophosphate.
2. How are purine bases salvaged? Add a note on Lesch-Nyhan syndrome.
Definition: It involves conversion of purines, purine ribonucleosides and purine deoxy
ribonucleosides to corresponding mononucleotides.
Reactions:
i. Phosphoribosylation of free purines.
Ch-14.indd 183 21-06-2014 11:51:44
