<scp>AICA</scp>‐ribosiduria due to <scp>ATIC</scp> deficiency: Delineation of the phenotype with three novel cases, and long‐term update on the first case

Ramond, Francis; Rio, Marlène; Héron, Bénédicte; Imbard, Apolline; Marie, Sandrine; Billiemaz, Kareen; Denommé‐Pichon, Anne‐Sophie; Kuentz, Paul; Ceballos, I.; Piraud, Monique; Vincent, Marie‐Françoise; Touraine, Renaud

doi:10.1002/jimd.12274

Cited by 24 publications

(31 citation statements)

References 42 publications

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“…Strikingly, specific substitutions of cetaceans (G106A and G113A), Tibetan antelope (V17E), and manatee (A110S) are found in the ATIC MGS-like domain. ATIC mutations affect the assembly of functional purinosomes ( Baresova et al, 2012 ; Ramond et al, 2020 ). A similar trend was also found in XDH .…”

Section: Discussionmentioning

confidence: 99%

Evolutionary impacts of purine metabolism genes on mammalian oxidative stress adaptation

Tian¹,

Yang²,

Chai³

et al. 2022

Zoological Research

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Many mammals risk damage from oxidative stress stemming from frequent dives (i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation), high altitude and subterranean environments, or powered flight. Purine metabolism is an essential response to oxidative stress, and an imbalance between purine salvage and de novo biosynthesis pathways can generate damaging reactive oxygen species (ROS). Here, we examined the evolution of 117 purine metabolism-related genes to explore the accompanying molecular mechanisms of enhanced purine metabolism in mammals under high oxidative stress. We found that positively selected genes, convergent changes, and nonparallel amino acid substitutions are possibly associated with adaptation to oxidative stress in mammals. In particular, the evolution of convergent genes with cAMP and cGMP regulation roles may protect mammals from oxidative damage. Additionally, 32 genes were identified as under positive selection in cetaceans, including key purine salvage enzymes (i.e., HPRT1 ), suggesting improved re-utilization of non-recyclable purines avoid hypoxanthine accumulation and reduce oxidative stress. Most intriguingly, we found that six unique substitutions in cetacean xanthine dehydrogenase (XDH), an enzyme that regulates the generation of the ROS precursor xanthine oxidase (XO) during ischemic/hypoxic conditions, show enhanced enzyme activity and thermal stability and diminished XO conversion activity. These functional adaptations are likely beneficial for cetaceans by reducing radical oxygen species production during diving. In summary, our findings offer insights into the molecular and functional evolution of purine metabolism genes in mammalian oxidative stress adaptations.

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Section: Discussionmentioning

confidence: 99%

Evolutionary impacts of purine metabolism genes on mammalian oxidative stress adaptation

Tian¹,

Yang²,

Chai³

et al. 2022

Zoological Research

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“…These events might be related to increased activation of the insulin pathway in hepatocytes in the context of ATIC deficiency. The involved variant (Ala136Thr) is located in the cyclohydrolase domain next to Lys 137, an amino acid crucial for the cyclohydrolase activity of dimeric ATIC [88]. The well-positioned Ala136Thr variant could thus drive metabolic comorbidities by decreasing ATIC connectivity in the PPIN.…”

Section: From Ppin To a T2d Disease Modulementioning

confidence: 99%

Insulin’s Discovery: New Insights on Its Hundredth Birthday: From Insulin Action and Clearance to Sweet Networks

Leroux

Boutchueng-Djidjou

Faure

2021

IJMS

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In 2021, the 100th anniversary of the isolation of insulin and the rescue of a child with type 1 diabetes from death will be marked. In this review, we highlight advances since the ingenious work of the four discoverers, Frederick Grant Banting, John James Rickard Macleod, James Bertram Collip and Charles Herbert Best. Macleoad closed his Nobel Lecture speech by raising the question of the mechanism of insulin action in the body. This challenge attracted many investigators, and the question remained unanswered until the third part of the 20th century. We summarize what has been learned, from the discovery of cell surface receptors, insulin action, and clearance, to network and precision medicine.

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“…To date, fewer than 100 patients have been identified with ADSL deficiency. Until quite recently, only one patient had been identified with AICA-ribosiduria (ATIC deficiency), but now, three more individuals (two are siblings) have been identified [10]. Finally, two individuals (siblings) have been identified with PAICS deficiency [11].…”

Section: Plos Onementioning

confidence: 99%

Transcriptome and metabolome analysis of crGART, a novel cell model of de novo purine synthesis deficiency: Alterations in CD36 expression and activity

et al. 2021

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In humans, GART [phosphoribosylglycinamide formyltransferase (EC 2.1.2.2) / phosphoribosylglycinamide synthetase (EC 6.3.4.13) / phosphoribosylaminoimidazole synthetase (EC 6.3.3.1)] is a trifunctional protein which catalyzes the second, third, and fifth reactions of the ten step de novo purine synthesis (DNPS) pathway. The second step of DNPS is conversion of phosphoribosylamine (5-PRA) to glycineamide ribonucleotide (GAR). 5-PRA is extremely unstable under physiological conditions and is unlikely to accumulate in the absence of GART activity. Recently, a HeLa cell line null mutant for GART was constructed via CRISPR-Cas9 mutagenesis. This cell line, crGART, is an important cellular model of DNPS inactivation that does not accumulate DNPS pathway intermediates. In the current study, we characterized the crGART versus HeLa transcriptomes in purine-supplemented and purine-depleted growth conditions. We observed multiple transcriptome changes and discuss pathways and ontologies particularly relevant to Alzheimer disease and Down syndrome. We selected the Cluster of Differentiation (CD36) gene for initial analysis based on its elevated expression in crGART versus HeLa as well as its high basal expression, high log2 value, and minimal P-value.

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AICA‐ribosiduria due to ATIC deficiency: Delineation of the phenotype with three novel cases, and long‐term update on the first case

Cited by 24 publications

References 42 publications

Evolutionary impacts of purine metabolism genes on mammalian oxidative stress adaptation

Evolutionary impacts of purine metabolism genes on mammalian oxidative stress adaptation

Insulin’s Discovery: New Insights on Its Hundredth Birthday: From Insulin Action and Clearance to Sweet Networks

Transcriptome and metabolome analysis of crGART, a novel cell model of de novo purine synthesis deficiency: Alterations in CD36 expression and activity

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