Lesch-Nyhan Sdr. and de novo purine synthesis

[glykon]

I'm a bit confused about Lesch-Nyhan syndrome.
In FA 2012, pg.70, they say that in Lesch-Nyhan sdr. you have excess uric acid production and de novo purine synthesis.Could someone pls explain why it increases de novo purine synthesis and give a mechanism? In the figure, there aren't any arrows going from inosine to IMP or adenosine or from guanosine to GMP...

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[Phloston]

I'm a bit confused about Lesch-Nyhan syndrome.
In FA 2012, pg.70, they say that in Lesch-Nyhan sdr. you have excess uric acid production and de novo purine synthesis.Could someone pls explain why it increases de novo purine synthesis and give a mechanism? In the figure, there aren't any arrows going from inosine to IMP or adenosine or from guanosine to GMP...

My guess would be that if you can't salvage your nucleotides, you need to create them from scratch --> increased de novo.

 

[Aclamity]

I'm a bit confused about Lesch-Nyhan syndrome.
In FA 2012, pg.70, they say that in Lesch-Nyhan sdr. you have excess uric acid production and de novo purine synthesis.Could someone pls explain why it increases de novo purine synthesis and give a mechanism? In the figure, there aren't any arrows going from inosine to IMP or adenosine or from guanosine to GMP...

The salvage pathway utilizes PRPP. Without HGPRT you don't go through the salvage pathway. All the excess PRPP that would've been used in the HGPRT reaction builds up and activates the de novo pathway (feed forward system)

 

[Phloston]

The salvage pathway utilizes PRPP. Without HGPRT you don't go through the salvage pathway. All the excess PRPP that would've been used in the HGPRT reaction builds up and activates the de novo pathway (feed forward system)

Nice. Good mechanism.

 

[glykon]

Thanks guys.