Cis-Aconitate

Optimal result: 10 – 36 mmol/mol creatinine

Iron deficiencies and overload at the systemic or cellular levels can negatively impact the aconitase enzyme and overall mitochondrial health and function. Due diligence with iron assessment is recommended when levels of these organic acids are abnormal. Glutathione may also be an important means of modulating aconitase activity during oxidative stress. Various toxins may influence mitochondrial enzymes and contribute to mitochondrial dysfunction, such as fluoride, aluminum, mercury, arsenic, and tin.

Possible causes:

- Impaired metabolism due to toxic metals (Fl, Hg, As) 
- OR low cofactors (Fe, GSH—depleted in oxidative stress)
- OR high amounts of dietary citric acid
- OR metabolic acidosis (if mildly increased cisaconitic acid but markedly increased citric acid).
- Low glutathione
- High amounts of dietary citric acid
- Metabolic acidosis (if mildly increased cis-aconitic acid but markedly increased citric acid)
- High levels can indicate ammonia toxicity or arginine insufficieny.
- An elevated level of this organic acid may be an indication of poor supplies or metabolism of amino acids. A clinical sign is fatigue.
- If elevated with orotate, isocitrate and citrate, suspect hyperammonia.
- High Citrate and Cis-aconitate can indicate arginine insufficiency for ammonia clearance through the Urea Cycle.

Additional investigations:

- Comprehensive Urine Elements Profile

- Functional Liver Detoxification Profile

- Complete Digestive Stool Analysis

Treatment considerations:

- Rule out toxic metals

- Glutathione-

- Consider supplementing with arginine and possibly cysteine.

Some foods high in argininer are:

- Pumpkin seeds

- Sesame seeds

- Dried walnuts

- Almonds

- Pine nuts

- Soy beans

- Chickpeas

- Seaweed

(Do not take L-arginine if you have had a recent heart attack.)

Additional investigations:

- Comprehensive Urine Elements Profile
- Functional Liver Detoxification Profile
- Complete Digestive Stool Analysis
- Rule out toxic metals and check for iron deficiency

cis-Aconitate is an Energy Production Marker. Low levels of these analytes may reflect insufficient precursors, or suboptimal glycolysis or fatty acid oxidation.

Possible correlation:

If cis-Aconitic Acid is measured to be low, and its precursor, citric acid, is also low:

In this case, the cis-aconitic acid deficiency is considered to be secondary to the subnormal citrate level; please refer to the commentary for low citrate.

Common Metabolic Association:

Amino Acid insufficiency

Possible causes:

Low or high pyruvic acid or low acetyCoA (from fatty acid oxidation).

Intervention Options:

Free-form amino acids

cis-Aconitate is involved in both energy production and removal of toxic ammonia.

A two-carbon group from Acetyl-CoA is transferred to oxaloacetate to form citric acid. Citric acid is then converted to isocitric acid through a cisaconitic intermediate using the enzyme aconitase. Aconitase is an iron-sulfate protein that controls iron homeostasis.

-----------------------

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. 

Citrate, cis-Aconitate (and Isocitrate) are involved in both energy production and removal of toxic ammonia.

High levels can indicate ammonia toxicity. Chronic loss of these valuable compounds can contribute to loss of organ reserve and disturbances in neurological function. If they are low they can indicate a need for essential amino acids, especially arginine.

Nutrient association: Arginine, Iron

References:

- Medline.gov - Arginine [L]

Cis-Aconitate
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