Table 1.
Overview of enzymes involved in proximal pyruvate metabolism
| Enzyme | Reaction | Metabolic deficiency symptoms | Incidence |
|---|---|---|---|
| Pyruvate dehydrogenase (PDH) | Pyruvate +NAD → CO2 + Acetyl-CoA + NADH | Neurodegeneration, lactic acidosis, hyperpyruvicemia, psychomotor retardation/developmental delay | Rare (350 + cases) [89, 90] |
| Lactate dehydrogenase (LDH) | Pyruvate + NADH ↔ lactate + NAD+ | Myoglobinuria, elevate pyruvate levels, low endurance/exercise intolerance | 1:1,000,000 [34, 294] |
| Pyruvate carboxylase (PC) | Pyruvate + ATP + CO2 → Oxaloacetate + ADP | Highly variable, depends upon classification (Types A, B, or C) May include lactic acidosis, developmental delay, and elevated proline and alanine levels | 1:250,000 [127] |
| Pyruvate kinase (PK) | Phosphoenolpyruvate + ADP → Pyruvate + ATP | Hemolytic anemia, hyperbilirubinemia | 1:20,000 [15] |
| Alanine aminotransferase (ALT) | Pyruvate + glutamate ↔ Alanine + α-ketoglutarate | Unknown (mild) | 2.5:1,000 [48] |
| Mitochondrial pyruvate carrier (MPC) | PyruvateIMS ↔ pyruvateMatrix | Neurodegeneration, lactic acidosis, hyperpyruvicemia, psychomotor retardation | Very rare (2 cases) [1, 68] |
| Pyruvate dehydrogenase phosphatase (PDP) | P-PDH → PDH + Pi | Lactic acidosis, elevated pyruvate and alanine levels, exercise intolerance, hypotonia | Very rare (2 cases) [113, 114] |
| Pyruvate dehydrogenase kinase (PDK) | PDH + ATP → P-PDH + ADP | N/A | N/A |
This table summarizes the reactions catalyzed by the enzymes involved in proximal pyruvate metabolism as well as the symptoms and incidences, where known, of the metabolic deficiencies characterized by their misregulation, mutation, or loss in human patients