Metabolomic changes in children with autism

Table 2 The roles, impact, potential biomarkers, genetic associations, and therapeutic implications of both purine and pyrimidine metabolism in the context of autism spectrum disorder

Aspect	Purine metabolism	Pyrimidine metabolism
Functions	Building blocks for nucleic acid synthesis; Metabolic signals; Provide energy; Regulate cell growth; Participate in coenzymes; Contribute to sugar transport; Donate phosphate groups in phosphorylation reactions	Synthesizing DNA and RNA; Energy metabolism; Neurotransmitter signaling
Specific roles	Provide energy for membrane-active pumps like Na+/K+ ATPase; Vital for sustaining synaptic transmission; Facilitate collaboration between neurons and glial cells	Biosynthesis of polysaccharides and phospholipids; Participate in detoxification processes; Contribute to protein and lipid glycosylation
Impact on brain function	Altered purine metabolism may impact brain function and contribute to ASD symptoms; Adenosine acts as a neuromodulator, inhibiting neurotransmitter release and regulating sleep-wake cycles	Abnormalities in pyrimidine metabolism may be linked to ASD and neurodevelopmental issues; Disturbances in uracil metabolism could contribute to mitochondrial dysfunction in ASD
Potential biomarkers	Elevated adenosine levels and altered ADA activity observed in ASD; Abnormal levels of purine metabolites such as uric acid reported in ASD	Altered uracil levels and abnormal ratios of uracil to other pyrimidine bases reported in ASD; Abnormal levels of pyrimidine nucleotides observed in ASD
Genetic associations	Mutations in genes encoding enzymes involved in purine metabolism found in individuals with ASD	Genetic mutations in the gene encoding DPD identified in individuals with ASD
Therapeutic implications	Modulating adenosine signaling and targeting enzymes involved in purine metabolism could potentially improve neurochemical functioning in ASD	Supplementation with pyrimidine precursors such as uridine was explored as a possible intervention to improve mitochondrial function and neurodevelopmental outcomes in ASD

ADA: Adenosine deaminase; ASD: autism spectrum disorder; ATP: Adenosine Triphosphate; DPD: dihydro-pyrimidine dehydrogenase.