Altered main metabolites pathway and dysregulated urea cycle in
AMN-SARS-CoV-2:
Pathway analysis conducted via PubChem and KEGG unveiled significantly
dysregulated pathways, including arginine biosynthesis, arginine and
proline metabolism, D-arginine and D-D-ornithine metabolism, glycine,
serine, and threonine metabolism, and D-amino acid metabolism
(Supplementary figure 1A and 1B). The dysregulated arginine metabolism
pathway was pivotal in AMN-SARS-CoV-2. Specifically, the urea cycle,
pivotal in arginine metabolism (Figure 2A), demonstrated a significant
role in AMN-SARS-CoV-2. Although plasma arginine levels showed no
significant variance between the AMN-SARS-CoV-2 and AMN-SARS-CoV-2-no
AMN groups in this study, notable increases were observed in ornithine
and citrulline levels within the AMN-SARS-CoV-2 group. Both are critical
intermediate metabolites in the urea cycle (Figure 2B), indicative of
urea cycle dysregulation in AMN-SARS-CoV-2. Furthermore, ornithine’s
capacity to convert into proline, utilized for synthesizing structural
proteins, particularly collagen involved in fibrosis, has been
reported[18]. In this study, the AMN-SARS-CoV-2 group demonstrated
significantly elevated proline levels compared to the AMN-SARS-CoV-2-no
AMN group (Figure 2B). Receiver operating characteristic (ROC) analysis
of ornithine, citrulline, and L-proline yielded an area under the curve
(AUC) values of 0.7704, 0.7296, and 0.7704, respectively (Figure 2C).