Anion Gap is a measure of the balance between positively and negatively charged electrolytes in the blood. An abnormal anion gap may indicate acid-base imbalances, kidney disease, or other health problems.
Acetylcarnitine is formed from acetyl-CoA, which if accumulated (e.g. due to PDH deficiency) can be hydrolyzed to acetate anions and increase the anion gap.
Morgan Nordstrom, L. O’Brien, Michael Hooper, Mark Flemmer, Paul Ellis Marik. “An unusual case of severe high anion gap metabolic acidosis”. BMC Research Notes (2011). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421581/
Aconitic acid is converted to isocitrate in the citric acid cycle. Elevated aconitic acid levels may slightly increase organic anions and the anion gap.
Francis G Bowling, Director of Biochemical Diseases, Mater Children’s Hospital. “Circulating anions usually associated with the Krebs cycle in patients with metabolic acidosis”. Critical Care (2006). https://ccforum.biomedcentral.com/articles/10.1186/cc4954
Like glutamic acid, aspartic acid is metabolized to organic anions (e.g. oxaloacetate) that can increase the anion gap if elevated.
J. A. Smith, A. R. Johnson, C. E. Williams, D. P. Evans. Aspartic Acid Isomerization Characterized by High Definition Mass Spectrometry Significantly Alters the Bioactivity of a Novel Toxin from Poecilotheria. Journal of Proteomics (2020). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232244/
Hydroxyglutaric acids are organic acid intermediates. Significant accumulation of these organic anions could increase the anion gap.
Duran, M., Abdenur, J. E., Farias, A. C., & Martins, E. V.. L-2-hydroxyglutaric aciduria – review of literature and case series. Journal of Inherited Metabolic Disease (1980). https://link.springer.com/article/10.1007%2FBF00487339
Lactic acid is a key contributor to the anion gap. Elevated lactic acid levels from anaerobic metabolism or impaired clearance can increase the anion gap.
Gunnerson, K. J., Saul, M., Kellum, J. A., & Palevsky, P.. Relationship Between the Anion Gap and Serum Lactate in Hypovolemic Shock. Critical Care Medicine (2022). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069407/
Succinic acid is an intermediate in the citric acid cycle. Accumulation of succinate anions can modestly contribute to an increased anion gap.
Kurtz, I., & Kraut, J. A.. Circulating anions usually associated with the Krebs cycle in patients with metabolic acidosis. Postgraduate Medical Journal (2005). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1297631/
