2. Conversion of IMP to AMP
IMP is converted to AMP in two enzymatic steps
Step-1: Donation of amino group by aspartate: Amino group of aspartate is enzymatically linked to the IMP (C6 of purine) coupled with GTP hydrolysis to form adenylosuccinate with the help of enzyme- adenylosuccinate synthetase.
Step-2: Eliminates fumarate group to form AMP: Adenylosuccinate is enzymatically converted to AMP by the removal of fumarate group with the help of enzyme adenylosuccinate lyase.

3. Conversion of IMP to AMP and GMP
Note: GTP is used for AMP synthesis.
IMP is the precursor for both AMP and GMP.

4. Conversion of IMP to GMP
IMP is converted to GMP in two enzymatic steps
Step-1:Dehydrogenation of IMP: IMP is enzymatically dehydrogenated to form Xanthosine Monophosphate (XMP) with the enzyme IMP dehydrogenase. The H+ ions released are accepted by NAD+.
Step-2: Amidation of XMP: In the second step, XMP is amidated with the amide group from glutamine with the presence of H2O and hydrolysis of ATP yields GMP (Guanosine monophosphate); catalyzed by the enzyme GMP synthetase.

5. ADP, ATP, GDP and GTP biosynthesis
kinase
kinase
AMP
ADP
ATP
ATP
ADP
ATP
ADP
kinase
kinase
GMP
GDP
GTP
ATP
ADP
ATP
ADP

6. Synthesis Of Purine Nucleotides By Salvage Pathway
Dr. Shumaila Asim
Lecture # 2

7. Salvage Pathways Since
De novo synthesis is expensive and
A few cells (e.g. RBCs) lack some enzymes involved in de novo synthesis (e.g. PRPP-amido-transferase)
Hence cells use salvage pathway (requiring far less energy and enzymes than de novo synthesis)

10. Salvage Pathway for Purine Nucleotides
Two pathways are available
a. One step pathway (phospho-ribosylation of purines)
(direct phospho-ribosylation of adenine, guanine and hypoxanthine)

12. Guanine
Phosphoribosyl
Tranferase

14. Salvage Pathway for Purine Nucleotides
b. A minor pathway is also available (phosphorylation of nucleoside)
ATP
ADP
Nucleoside kinase
Purine – Ribose
A or G
Purine–Ribose–Phosphate
AMP or GMP

15. Synthesis of Deoxyribonucleotides:
Deoxyribonucleotides are synthesized from their corresponding ribonucleotides by the reduction of ribose sugar at position C2’.
The Enzymes in the formation of deoxyribonucleotides by the reduction of the corresponding ribonucleotides are called ribonucleotide reductases (RNRs).
The enzyme is ribonucleotide reductase complex.Active only when cells are actively synthesizing DNA.
It requires thioredoxin, thioredoxin reductase and NADPH.

17. Synthesis of Deoxy-ribonucleotide

18. Regulation of ribonucleotide reductase

19. Regulatory Control of Purine Biosynthesis
Above the level of IMP production:
Independent control
Synergistic control
Feedforward activation by PRPP
Below level of IMP production
Reciprocal control
Total amounts of purine nucleotides controlled
Relative amounts of ATP, GTP controlled

20. Purine nucleotide biosynthesis is regulated by feedback inhibition

21. Summary of purine biosynthesis
IMP

22. Catabolism of Purine Nucleotides

25. Degradation of purines
Uric acid is the end product in humans
Uric acid = alloxan + urea
Excreted mainly through kidneys ( mg/day)
Some mammals contain uricase, which converts uric acid to a highly water-soluble product, allantoin 

30. Assignment first week (Practical Copy)
Tabulate the biochemical characteristics of adenosine, guanosine, cytidine and uridine derivatives marks
Draw and label the sources of atoms of Purine and Pyrimidine nucleus marks
Flow chart showing conversion of IMP to AMP and GMP with enzymes and co-enzymes marks
A flow sheet describing Purine degradation with enzymes and co-enzymes marks