Metabolic small molecule disease biomarkers are low molecular weight metabolites whose abnormal levels indicate metabolic disturbances or diseases. These biomarkers are critical in metabolic profiling (metabolomics) and offer insights into disease mechanisms, diagnostics, and treatment monitoring.
🧪 Key Features
- Typically include amino acids, organic acids, lipids, sugars, and nucleotides
- Found in blood, urine, CSF, saliva, etc.
- Identified via LC-MS/MS, GC-MS, NMR, or biosensors
📋 List of Metabolic Small Molecule Biomarkers by Disease
| Disease/Disorder | Biomarker(s) | Role/Indication |
| Diabetes Mellitus | Glucose, ketone bodies (β-hydroxybutyrate, acetoacetate), lactate | Glucose metabolism dysfunction; ketoacidosis marker |
| Inborn Errors of Metabolism | Phenylalanine (PKU), methylmalonic acid (MMA), isovalerylglycine | Diagnostic markers in newborn screening |
| Cardiovascular Disease | Trimethylamine-N-oxide (TMAO), homocysteine, arginine | Atherosclerosis, endothelial dysfunction |
| Cancer | 2-Hydroxyglutarate (2-HG), sarcosine, choline derivatives | Oncometabolites; linked to IDH mutations, prostate cancer |
| Liver Disease | Ammonia, bile acids, bilirubin | Indicators of hepatic dysfunction and urea cycle defects |
| Kidney Disease | Creatinine, urea, uric acid | Glomerular filtration rate and nitrogenous waste levels |
| Neurodegenerative Disease | 3-Hydroxykynurenine, GABA, glutamate | Altered in Alzheimer’s, Parkinson’s, Huntington’s diseases |
| Mitochondrial Disorders | Lactate, pyruvate, succinate | Indicators of mitochondrial dysfunction |
| Obesity/Metabolic Syndrome | Leptin, adiponectin, branched-chain amino acids (BCAAs: valine, leucine, isoleucine) | Insulin resistance, metabolic imbalance |
| Sepsis/Acidosis | Lactate | Marker of hypoperfusion and metabolic acidosis |
🧬 Common Biomarker Classes in Metabolic Diseases
| Class | Examples |
| Amino acids | Phenylalanine, tyrosine, glutamine, BCAAs |
| Organic acids | Lactic acid, pyruvate, methylmalonic acid |
| Sugars | Glucose, galactose, fructose |
| Lipids | Free fatty acids, TMAO, phosphatidylcholine |
| Nucleotides | Hypoxanthine, uric acid |
🔍 Applications
- Newborn screening (e.g., PKU, MSUD)
- Early disease detection (e.g., insulin resistance)
- Monitoring therapy (e.g., amino acid levels in metabolic diets)
- Drug development (e.g., metabolic pathway targets)