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 cis-aconitic intermediate using the enzyme aconitase. Aconitase is an iron-sulfate protein that controls iron homeostasis.
References:
- Bullock GC, Delehanty LL, Talbot A-L, et al. Iron control of erythroid development by a novel aconitase-associated regulatory pathway. Blood. 2010;116(1):97-108.
- Paul BT, Manz DH, Torti FM, Torti SV. Mitochondria and Iron: current questions. Expert Rev Hematol. 2017;10(1):65-79. 120. Han D, Canali R, Garcia J, Aguilera R, Gallaher TK, Cadenas E. Sites and Mechanisms of Aconitase Inactivation by Peroxynitrite: Modulation by Citrate and Glutathione. Biochemistry. 2005;44(36):11986-11996.
- Pace C, Dagda R, Angermann J. Antioxidants protect against arsenic induced mitochondrial cardio-toxicity. Toxics. 2017;5(4):38.
- Zatta P, Lain E, Cagnolini C. Effects of aluminum on activity of Citric Acid Cycle enzymes and glutamate dehydrogenase in rat brain homogenate. Eur J Biochem. 2000;267(10):3049-3055.
- Carocci A, Rovito N, Sinicropi MS, Genchi G. Mercury toxicity and neurodegenerative effects. In: Rev Environ Contam Toxicol. Springer; 2014:1-18.
- Houston MC. The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction. Altern Ther Health Med. 2007;13(2):S128-S133.
Low levels of these analytes may reflect insufficient precursors, or suboptimal glycolysis or fatty acid oxidation.
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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.
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% Omega-3s, % Omega-6s, % Omega-9s, % Saturated Fats, 1-Methylhistidine, 3-Hydroxyisovaleric Acid, 3-Hydroxyphenylacetic Acid, 3-Hydroxypropionic Acid, 3-Methyl-4-OH-phenylglycol, 3-Methylhistidine, 4-Hydroxyphenylacetic Acid, 5-OH-indoleacetic Acid, 8-OHdG (urine), a-Amino-N-butyric Acid, a-Aminoadipic Acid, a-Hydroxybutyric Acid, a-Hydroxyisobutyric Acid (from MTBE), a-Keto-b-Methylvaleric Acid, a-Ketoadipic Acid, a-Ketoglutaric Acid, a-Ketoisocaproic Acid, a-Ketoisovaleric Acid, a-Ketophenylacetic Acid (from Styrene), a-Linolenic (ALA) 18:3 n3, AA / EPA (20:4 n6 / 20:5 n3), Adipic Acid, Alanine, Aluminum, Anserine (dipeptide), Antimony, Arachidic C20:0, Arachidonic (AA) 20:4 n6, Arginine, Arsenic, Asparagine, Aspartic Acid, b-Alanine, b-Aminoisobutyric Acid, b-OH-b-Methylglutaric Acid, b-OH-Butyric Acid, Barium, Behenic C22:0, Benzoic Acid, Bismuth, Cadmium, Calcium, Carnosine (dipeptide), Cesium, Chromium, cis-Aconitic Acid, Citramalic Acid, Citric Acid, Citrulline, Cobalt, Copper, Creatinine, Creatinine Concentration (Amino Acids FMV), Cystathionine, Cysteine, Cystine, D-Arabinitol, Dihomo-g-linolenic (DGLA) 20:3 n6, Dihydroxyphenylpropionic Acid (DHPPA), Docosahexaenoic (DHA) 22:6 n3, Docosapentaenoic (DPA) 22:5 n3, Docosatetraenoic (DTA) 22:4 n6, Eicosadienoic 20:2 n6, Eicosapentaenoic (EPA) 20:5 n3, Elaidic 18:1 n9t, Ethanolamine, Formiminoglutamic Acid (FIGlu), g-Aminobutyric Acid, g-Linolenic (GLA) 18:3 n6, Gadolinium, Gallium, Glutamic Acid, Glutamine, Glutaric Acid, Glyceric Acid, Glycine, Glycolic Acid, Hippuric Acid, Histidine, Homovanillic Acid, Indoleacetic Acid, Iron, Isocitric Acid, Isoleucine, Isovalerylglycine, Kynurenic / Quinolinic Ratio, Kynurenic Acid, Lactic Acid, Lead, Leucine, Lignoceric C24:0, Linoleic (LA) 18:2 n6, Linoleic / DGLA (18:2 n6 / 20:3 n6), Lipid Peroxides (urine), Lithium, Lysine, Magnesium, Malic Acid, Manganese, Margaric C17:0, Mercury, Methionine, Methylmalonic Acid, Molybdenum, Nervonic 24:1 n9, Nickel, Niobium, Oleic 18:1 n9, Omega-3 Index, Omega-6s /Omega-3s, Ornithine, Orotic Acid, Oxalic Acid, Palmitic C16:0, Palmitoleic 16:1 n7, Pentadecanoic C15:0, Phenylacetic Acid, Phenylalanine, Phosphoethanolamine, Phosphoserine, Platinum, Potassium, Proline, Pyroglutamic Acid, Pyruvic Acid, Quinolinic Acid, Rubidium, Sarcosine, Selenium, Serine, Stearic C18:0, Strontium, Suberic Acid, Succinic Acid, Sulfur, Tartaric Acid, Taurine, Thallium, Thorium, Threonine, Tin, Tricosanoic C23:0, Tryptophan, Tungsten, Tyrosine, Uranium, Urea, Urine Creatinine, Vaccenic 18:1 n7, Valine, Vanadium, Vanilmandelic Acid, Xanthurenic Acid, Zinc
