Table 1.
Thirteen Urinary Metabolite Biomarkers for DKD and Their Associated Enzymes and Pathways
| Metabolite Decreased in DKD |
HMDB ID of Metabolite |
Function in Intermediary Metabolism |
Enzyme(s) Producing the Metabolite | Subcellular location of Enzymes |
|---|---|---|---|---|
| 3-Hydroxyisovaleric acid | HMDB00754 | Leu metabolite | 3-methylglutaconyl CoA hydratase | Mitochondria |
| Glycolic acid | HMDB00115 | Gly (peroxisomes) and 4-hydroxyproline (mitochondria) | NADPH-glyoxylate reductase | Peroxisomes, mitochondria |
| Citric acid | HMDB00094 | The TCA cycle and lipid synthesis | Citrate synthase | Mitochondria |
| 2-Ethylhydracrylic acid | HMDB00396 | Ile metabolite | From R-pathway of Ile metabolism (with 2MBDH deficiency) | Mitochondria |
| Uracil | HMDB00300 | Pyrimidine synthesis | Coenzyme Q10: dihydroorotate dehydrogenase, UMPS | Mitochondria |
| 3-Hydroxyisobutyric acid | HMDB00023 | Val metabolite | 3HIBCH | Mitochondria |
| Aconitic acid | HMDB00072 | The TCA cycle | Aconitase | Mitochondria |
| 3-Methyladipic acid | HMDB00555 | Indicates incomplete BCFA oxidation | From decreased intake of phytanic acid or increased α-oxidation of BAFA | Mitochondria |
| Tiglylglycine | HMDB00959 | Ile metabolite | FAD and 2MBDH | Mitochondria |
| 3-Methylcrotonylglycine | HMDB00459 | Leu metabolite | FAD and IVD | Mitochondria |
| 2-Methylacetoacetic acid | HMDB03771 | Ile metabolite | NAD+ and MHBD | Mitochondria |
| Homovanillic acid | HMDB00118 | Dopamine metabolite | COMT and MAO | Cytosol, Mitochondria |
| Hydroxypropionic acid | HMDB00700 | Ile, Val, Thr, and Met metabolite | 2MAACT (Ile), NAD+ and MMSDH (Val), NAD+ and 2KBDH (Thr and Met) | Mitochondria |
Abbreviations: 2MAACT, 2-methylacetoacetyl Coa thiolase; 2MBDH, 2-methylbutyryl-CoA dehydrogenase; 2KBDH, 2-ketobutyrate dehydrogenase; 3HIBCH, 3-hydroxyisobutryl-CoA hydrolase; BAFA, branched-chain fatty acids; COMT, catechol-O-methyl transferase; FAD, flavin adenine dinucleotide; Gly, glycine; Ile, isoleucine; IVD, isovaleryl-CoA dehydrogenase; Leu, leucine; MAO, monoamine oxidase; Met, methionine; MHBD, 2-methyl-3-hydroxybutyryl CoA dehydrogenase; MMSDH, methylmalonate semialdehyde dehydrogenase; NAD+, nicotinamide adenine dinucleotide; Thr, threonine; UMPS, uridine monophosphate synthetase; Val, valine.
Adapted with permission from Sharma et al.20