Metabolism Of Purine

Hypoxanthine andAdenine

Humans convert adenosine and guanosine to uric acid. Adenosine is first converted to inosine by adenosine deaminase. In mammals other than higher primates, uricase converts uric acid to the water-soluble product allantoin. However, since humans lack uricase, the end product of purine catabolism in humans is uric acid.  

“The nucleoside is composed of purine purine or pyrimidine base linked to either D-ribose (in RNA) or D-2- deoxyribose (in DNA)”

• Nucleotides are nucleoside +P
• The Phosphodiester bond between the nucleotides is formed mainly between 3’OH group of sugar of one nucleotide to 3’OH group of sugar of another nucleotide.

D i.e. Allantoin

A i.e. tRNA

Biosynthesis of purine

• N1 of purine is derived from amino group of aspartate
• N3 and N9 are obtained from amide group of glutamine
• C4, C5 and N7 of the purine ring of nucleotides are contributed by glycine

The liver is the major organ of de novo synthesis of all four nucleotides.

Degradation in humans, however, is only complete for pyrimidines (C, T, U), but not purines (G, A), which are excreted from the body in form of uric acid

In de novo synthesis, purine ring is formed from variety of precursors is assembled on ribose-5-phosphate. Precursors for de novo synthesis are –

i)      Glycine provides C₄, C₅ and N₇

ii)     Aspartate provides N₁

iii)    Glutamine provides N₃ and N₉

iv)   Tetrahydrofolate derivatives furnish C₂ and C₈

v)    Carbon dioxide provides C₆

• Humans catabolize purines to uric acid.
• But, first purines are catabolized to xanthine, which is further catabolized to purine.

The biosynthesis of purine begins with ribose-5-phosphate, derived from pentose phosphate pathway (PPP).

First intermediate formed in this pathway, 5-phosphoribosyl-pyrophosphate (PRPP), is also an intermediate in purine salvage pathway.

Purine nucleotide synthesis occurs by two pathways :

1.De novo synthesis

2.Salvage pathway

Liver is the major site of purine nucleotide biosynthesis (de novo).

Certain tissues cannot synthesize purine nucleotides by de novo patyway, e g. brain, erythrocytes and polymor­phonuclear leukocytes.

These are dependent on salvage pathway for synthesis of purine nucleotides by using exogenous purines, which are formed by degradation of purine nucleotides synthesized in liver.

Ans. is ‘d’ i.e., Uric acid

PRPP glutamyl amidotransferase is one of the rate limiting enzyme in de novo synthesis of purines. o The de novo synthesis of purines is most active in liver.

Brain, RBCs (erythrocytes) and polymorphonuclear leokocytes (polymorphs) cannot synthesize purine nucleotides by de novo pathway.

Biosynthesis of purine neucleotides

Two important purine nucleotides are synthesized : (i) adenosine monophosphate (AMP) and (ii) guanosine monophosphate (GMP). Then AMP and GMP are converted to other purine nucleotides like ADP, ATP, GDP, GTP etc. Purine nucleotides can be synthesized by two pathways – (I) De novo synthesis and (2) Salvage pathway.

De novo pathway (De novo synthesis)

In de novo pathway, the purine nucleotides are synthesized from amphibolic intermediates. Amphibolic intermediates are the intermediary metabolites of amphibolic pathways (eg. citric acid cycle) which have dual purposes, i e. they serve in catabolism as well as in anabolism.

In de novo synthesis, purine ring is formed from variety of precursors is assembled on ribose-5-phosphate. Precursors for de novo synthesis are ‑

i)  Glycine provides C4 C5 and N7

ii)  Aspartate provides NI

iii)  Glutamine provides N3 and N9

iv)  Tetrahydrofolate derivatives furnish C2 and Cs

v)  Carbon dioxide provides C6

Purine nucleotide synthesis occurs by two pathways :-

1.De novo synthesis

2.Salvage pathway

Liver is the major site of purine nucleotide biosynthesis (de novo).

Certain tissues cannot synthesize purine nucleotides by de novo patyway, e g. brain, erythrocytes and polymorphonuclear leukocytes.

These are dependent on salvage pathway for synthesis of purine nucleotides by using exogenous purines, which are formed by degradation of purine nucleotides synthesized in liver.

Ans. is ‘b’ i.e., Liver

• Purine nucleotide synthesis occurs by two pathways :
• De novo synthesis
• Salvage pathway
• Liver is the major site of purine nucleotide biosynthesis (de novo).
• Certain tissues cannot synthesize purine nucleotides by de novo patyway, e g. brain, erythrocytes and polymorphonuclear leukocytes.
• These are dependent on salvage pathway for synthesis of purine nucleotides by using exogenous purines, which are formed by degradation of purine nucleotides synthesized in liver.

Ans. is ‘b’ i.e., Uric acid

Ans. is ‘c’ i.e., Synthesis of purine nucleotides from purine bases

• Two important purine nucleotides are synthesized : (i) adenosine monophosphate (AMP) and (ii) guanosine monophosphate (GMP). Then AMP and GMP are converted to other purine nucleotides like ADP, ATP, GDP, GTP etc. Purine nucleotides can be synthesized by two pathways – (1) De novo synthesis and (2) Salvage pathway. De novo pathway (De novo synthesis)
• In de novo pathway, the purine nucleotides are synthesized from amphibolic intermediates. Amphibolic intermediates are the intermediary metabolites of amphibolic pathways (eg. citric acid cycle) which have dual purposes, i e. they serve in catabolism as well as in anabolism.
• In de novo synthesis, purine ring is formed from variety of precursors is assembled on ribose-5-phosphate. Precursors for de novo synthesis are ‑

1. Glycine provides Ca, C5 and N7
2. Aspartate provides N,
3. Glutamine provides N3 and N9
4. Tetrahydrofolate derivatives furnish C₂ and C8
5. Carbon dioxide provides Co

Salvage pathway of purine nucleotide synthesis

• Free purine bases (adenine, guanine and hypoxanthine) and purine nucleosides are formed in cells during the metabolic degradation of nucleic acids and nucleotides.
• These free purine bases and purine nucleosides are reused in the formation of purine nucleotides. 
• This is called salvage pathway (salvage means property saved from loss).
• Salvage synthesis requires far less energy than de novo synthesis.