Inborn Errors of Purine Salvage and Catabolism

Abstract

Cellular purine nucleotides derive mainly from de novo synthesis or nucleic acid turnover and, only marginally, from dietary intake. They are subjected to catabolism, eventually forming uric acid in humans, while bases and nucleosides may be converted back to nucleotides through the salvage pathways. Inborn errors of the purine salvage pathway and catabolism have been described by several researchers and are usually referred to as rare diseases. Since purine compounds play a fundamental role, it is not surprising that their dysmetabolism is accompanied by devastating symptoms. Nevertheless, some of these manifestations are unexpected and, so far, have no explanation or therapy. Herein, we describe several known inborn errors of purine metabolism, highlighting their unexplained pathological aspects. Our intent is to offer new points of view on this topic and suggest diagnostic tools that may possibly indicate to clinicians that the inborn errors of purine metabolism may not be very rare diseases after all.

The prevalence of ADSL (rs3788579) and CYP1A2 (rs17861162) polymorphisms in female breast cancer patients in North-West Iran

“…The ADSL gene exhibits typical characteristics of a housekeeping gene [ 53 ]. Functioning as an essential homotetrameric enzyme, ADSL plays a pivotal role in two key reactions: 1) the conversion of succinylaminoimidazolecarboxamide (SAICA)-ribotide (SAICAR) into AICA-ribotide (AICAR) through the de novo purine synthesis pathway, and 2) the generation of AMP by converting adenylo-succinate into adenosine monophosphate as part of the purine nucleotide cycle [ 54 ]. Potential modifications to the purine nucleotide degradation pathway resulting from non-synonymous SNPs in the ADSL gene could lead to structural or functional alterations in its associated protein [ 55 ].…”

Interplay between mTOR and Purine Metabolism Enzymes and Its Relevant Role in Cancer

“…The enzyme catalyzes the formation of AICAR from succinyl-AICAR (SAICAR) in the “de novo” pathway, and also the conversion of succinyl-AMP (S-AMP) into AMP, thus participating in the “AMP cycle” ( Figure 1 ). ADSL deficiency is a rare genetic disorder, causing severe neurological symptoms, the etiology of which is still under investigation [ 66 ]. Conversely, the expression of ADSL has been found to significantly increase in several tumors [ 63 , 67 , 68 , 69 ] and the prevalence of ADSL-rs3788579 polymorphism has been recently reported in female cancer patients in North-West Iran [ 70 ].…”