Table 1.

List of toxic metabolites.

Category	Toxic metabolite	Related pathway	Ref supporting toxic property
ROSgens	Hydrogen selenide	Selenocysteine synthesis	[27, 28, 113]
	Bilirubin	Heme degradation	[29–33]
	Hypoxanthine	Purine metabolism	[34, 35]
	Agmatine	Arginine catabolism	[36, 37]
	Spermidine	Arginine catabolism	[38, 41]
	Spermine	Arginine catabolism	[39–41]
	3-Hydroxyanthranilate	Tryptophan degradation	[42, 43]
	Cysteamine	Taurine synthesis	[44–46]
Reactive metabolites (Aldehydes, reactive to thiols, etc.)	Formaldehyde	By product of oxidative demethylation/deamination	[20, 115]
	Malondialdehyde	Lipid peroxidation byproduct	[49]
	4-hydroxynonenal	Lipid peroxidation byproduct	[50, 51]
	Crotonaldehyde	Lipid peroxidation byproduct	[52]
	4-oxononenal	Lipid peroxidation byproduct	[51]
	Acrolein	Lipid peroxidation byproduct	[53]
	3,4-dihydroxyphenylacetaldehyde	Dopamine degradation	[54]
	Methylglyoxal	Various	[55–59]
	Methacrylyl-CoA	Valine catabolism	[60, 61]
	Glutaconyl-CoA	Valine catabolism	[62]
	Xanthurenic Acid	Tryptophan degradation	[63, 64]
Toxic analogs	dUTP	Nucleotide synthesis	[69–71]
	S-adenosylhomocysteine	Transmethylation	[72–74]
	L-2-hydroxyglutarate	Promiscuous reaction of LDH and MDH	[77–83]
Excitotoxins	Quinolinic acid	Kynurenine degradation	[85, 86]
	3-hydroxyglutaric acid	Kynurenine degradation	[87, 88]
	Glutaric acid	Kynurenine degradation	[88]
	Homocysteine	Homocysteine synthesis	[89–91]
Not Established	Dehydroepiandrosterone	Steroid hormone synthesis	[94–98]
	Ceramide	Sphingolipid synthesis	[99, 100]
	Squalene	Steroid hormone synthesis	[101–103, 116]
	4-methylthio-2-oxobutanoate	Methionine salvage pathway	[104, 105]
	Fumarylacetoacetate	Tyrosine degradation	[107–109]
	Gangliosides	Ganglioside synthesis	[110, 111]
	ex) Ganglioside GM3	Ganglioside synthesis	[117–119]
	ex) Ganglioside GD3	Ganglioside synthesis	[120–122]