The key role of purine metabolism in the folate-dependent phenotype of autism spectrum disorders: An in silico analysis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F20%3A10410897" target="_blank" >RIV/00216208:11130/20:10410897 - isvavai.cz</a>

Alternative codes found

RIV/00064203:_____/20:10410897

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=_oW5XJrUJx" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=_oW5XJrUJx</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/metabo10050184" target="_blank" >10.3390/metabo10050184</a>

Result language

angličtina

Original language name

The key role of purine metabolism in the folate-dependent phenotype of autism spectrum disorders: An in silico analysis

Original language description

Folate deficiency in the critical developmental period has been repeatedly associated with an increased risk of Autism spectrum disorders (ASD), but the key pathophysiological mechanism has not yet been identified. In this work, we focused on identifying genes whose defect has similar consequences to folate depletion in the metabolic network. Within the Flux Balance Analysis (FBA) framework, we developed a method of blocked metabolites that allowed us to define the metabolic consequences of various gene defects and folate depletion. We identified six genes (GART, PFAS, PPAT, PAICS, ATIC, and ADSL) whose blocking results in nearly the same effect in the metabolic network as folate depletion. All of these genes form the purine biosynthetic pathway. We found that, just like folate depletion, the blockade of any of the six genes mentioned above results in a blockage of purine metabolism. We hypothesize that this can lead to decreased adenosine triphosphate (ATP) and subsequently, an S-adenosyl methionine (SAM) pool in neurons in the case of rapid cell division. Based on our results, we consider the methylation defect to be a potential cause of ASD, due to the depletion of purine, and consequently S-adenosyl methionine (SAM), biosynthesis. (C) 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10600 - Biological sciences

Project

<a href="/en/project/LM2018132" target="_blank" >LM2018132: The National Center for Medical Genomic</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Metabolites

ISSN

2218-1989

e-ISSN

—

Volume of the periodical

10

Issue of the periodical within the volume

5

Country of publishing house

CH - SWITZERLAND

Number of pages

16

Pages from-to

184

UT code for WoS article

000539315800013

EID of the result in the Scopus database

2-s2.0-85084266855