Biomarkers

Target: Citric acid

Citric acid (citrate) is a tricarboxylic acid, an organic acid with three carboxylate groups. Citrate is an intermediate in the TCA cycle (also known as the Tricarboxylic Acid cycle, the Citric Acid cycle or Krebs cycle). The TCA cycle is a central metabolic pathway for all animals, plants, and bacteria. As a result, citrate is found in all living organisms, from bacteria to plants to animals. In the TCA cycle, the enzyme citrate synthase catalyzes the condensation of oxaloacetate with acetyl CoA to form citrate. Citrate then acts as the substrate for the enzyme known as aconitase (EC 4.2.1.3) and is then converted into aconitic acid. The TCA cycle ends with regeneration of oxaloacetate. This series of chemical reactions in the TCA cycle is the source of two-thirds of the food-derived energy in higher organisms. Citrate can be transported out of the mitochondria and into the cytoplasm, then broken down into acetyl-CoA for fatty acid synthesis, and into oxaloacetate. Citrate is a positive modulator of this conversion, and allosterically regulates the enzyme acetyl-CoA carboxylase, which is the regulating enzyme in the conversion of acetyl-CoA into malonyl-CoA (the commitment step in fatty acid synthesis). In short, citrate is transported into the cytoplasm, converted into acetyl CoA, which is then converted into malonyl CoA by acetyl CoA carboxylase, which is allosterically modulated by citrate. In mammals and other vertebrates, citrate is a vital component of bone, helping to regulate the size of apatite crystals (PMID: 21127269 ). Citric acid is found in citrus fruits, most concentrated in lemons and limes, where it can comprise as much as 8% of the dry weight of the fruit. Citric acid is a natural preservative and is also used to add an acidic (sour) taste to foods and carbonated drinks. Because it is one of the stronger edible acids, the dominant use of citric acid is as a flavouring and preservative in food and beverages, especially soft drinks and candies. Citric acid is an excellent chelating agent, binding metals by making them soluble. It is used to remove and discourage the buildup of limescale from boilers and evaporators. It can be used to treat water, which makes it useful in improving the effectiveness of soaps and laundry detergents. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. Intolerance to citric acid in the diet is known to exist. Little information is available as the condition appears to be rare, but like other types of food intolerance it is often described as a "pseudo-allergic" reaction. The evaluation of plasma citric acid is infrequently used in the diagnosis of human diseases. On the contrary, urinary citrate excretion is a common tool in the differential diagnosis of kidney stones, renal tubular acidosis and it also plays a role in bone diseases. Low urinary citrate excretion is a known risk factor for the development of kidney stones. Citrate inhibits stone formation by complexing with calcium in the urine, inhibiting spontaneous nucleation, and preventing growth and agglomeration of crystals. Hypocitraturia is a common metabolic abnormality found in 20% to 60% of stone formers (PMID: 19918339). In individuals with hypocitraturia, citric acid is found to be decreased at concentrations less than 320 mg (1.67 mmol) per day compared to normal individuals with concentrations ranging from 320 to 1,240 mg (PMID: 6823713, PMID: 19918339). Citric acid has also been looked into as a possible biomarker for prostate cancer (PMID: 35323711). It has been shown to be elevated in urine of individuals with prostate cancer at an average concentration of 0.00016 μM ± 0.00016 μM compared to normal individuals with an average concentration of 0.00006 ± 0.00006 μM (PMID: 35323711). A similar trend was observed in serum samples of prostate cancer patients.