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. 2024 Oct 30;25(21):11636. doi: 10.3390/ijms252111636

Figure 3.

Figure 3

The impact of machine learning-identified metabolites on multiple body systems. Metabolites damaging cardiovascular system when levels are decreased: lignoceroylsphingomyelin, sphingomyelin (d18:1/25:0), behenoyldihydrosphingomyelin, and homoarginine. Metabolites damaging renal system when levels are increased: 3-amino-2-piperidone, N-acetylphenylalanine, C-glycosyltryptophan, 5-galactosyllysine, hydroxyasparagine, 3-ureidopropionate, and homocitrulline. Metabolites damaging renal system when levels are decreased: homoarginine. Metabolites damaging respiratory system when levels are increased: 3-amino-2-piperidone, C-glycosyltryptophan, 5-galactosyllysine, 1-methyl-4-imidazoleacetate, and 2-hydroxyfluorene sulfate. Metabolites damaging central nervous system when levels are increased: 3-amino-2-piperidone, oleoylethanolamide, and 5-hydroxyhexanoate. Metabolites damaging endocrine system when levels are increased: (S)/(R)-hydroxybutyrate, N-acetylglucosamine, and mannose. Metabolites damaging antioxidant system when levels are decreased: N-acetylcarnosine. Detailed information about mechanisms exerted by these metabolites can be found in Figures S10–S12. Abbreviations: CA, carnitine; H, hydroxy; HM, hydroxybutyrate; ILA, imidazoleacetate; OEA, oleylethanolamide; SM, sphingomyelin; UPA, ureidopropionate. Metabolites damaging cardiovascular system when levels are increased: 3-amino-2-piperidone, N-acetylphenylalanine, C-glycosyltryptophan, subeoylcarnitine, 9-hydroxystearate, 3-hydroxyadipate, sphinganine, malate, 5-hydroxymethyl-2-furoylcarnitine, caprate, and homocitrulline. Lysine can replace ornithine in the urea cycle and combine with arginine to form homoarginine (Figure S8A). An increase in homoarginine was inversely associated with mortality in our study, in agreement with the findings in the LURIC and 4D studies [26]. Homoarginine acts as a nitric oxide precursor, enhancing endothelial function [26]. Elevated homocitrulline and decreased homoarginine result in disruption of the lysine pathway and increases the risk of mortality [15].