Isocitrate

Impaired metabolism due to toxic metals (Fl, Hg, As, Sb) OR low cofactors (Fe, GSH— depleted in oxidative stress); OR high amounts of dietary citric acid; OR metabolic acidosis (if mildly increased cis-aconitic acid but markedly increased citric acid). High Citrate and Cis-aconitate can indicate arginine insufficiency for ammonia clearance through the Urea Cycle Consider supplementing with arginine Rule out toxic metals; glutathione, N-acetylcysteine, Mg, or L-glutamine; consider antioxidants; rule out pancreatic insufficiency (can lead to metabolic acidosis from deficient bicarbonate).

Possible causes:

• Impaired metabolism due to toxic metals (Fl, Hg, As)
• Low glutathione
• High amounts of dietary citric acid
• Metabolic acidosis (if mildly increased cis-aconitic acid but markedly increased citric acid)

Additional investigations:

• Comprehensive Urine Elements Profile
• Functional Liver Detoxification Profile
• Complete Digestive Stool Analysis

Treatment considerations:

• Rule out toxic metals
• Glutathione

Lower levels:

- Might be due to low or high pyruvic acid or low acetyCoA (from fatty acid oxidation)

- 2° to subnormal upstream metabolites. 

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If Isocitric Acid is measured to be subnormal: 

This may be due to deficient or low-normal levels of its precursors, cis-aconitate or citrate. It may also be due to depleted alpha-ketoglutarate, which it forms in the citric acid cycle. 

### check for low alpha-ketoglutarate

The same enzyme, aconitase, forms cis-aconitic acid and isocitric acid, and requires reduced cysteine or glutathione and ferrous iron (Fe+2). Oxidant stress can inhibit it, as can arsenic, mercury or antimony. Fluoride that becomes fluorocitrate can strongly inhibit aconitase and impair formation of isocitrate.

Citric acid, cis-aconitic acid, and isocitric acid are the first three metabolites in the Krebs Citric Acid energy production cycle, which operates in the mitochondria of your cells.