Citrase

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Citrate usually refers to tri-n-butyl citrate, its chemical name is 3-hydroxy-3-carboxyglutarate tributyl, which is a kind of ester compound, colorless and transparent liquid with high boiling point, slightly soluble in water, and most organic solvents are miscible. Industrially, it is formed by the reaction of citric acid and n-butanol. It can be directly used as a plasticizer, or it can be further processed into a plasticizer with excellent performance, acetyl tributyl citrate. This product is low-toxic and can be regarded as a non-toxic plasticizer. It is commonly known as an environmentally friendly plasticizer. It can replace phthalate plasticizers with restricted applications.

Figure 1. Structure of citrase.

Introductions

TBC molecular formula C₁₈H₃₂O₇, molar mass 360·44 g/mol, is a colorless or light yellow liquid, can be mixed with acetone, CCl₄, mineral oil, acetic acid, castor oil, alcohol and their solvents; insoluble in water, non-toxic and tasteless, Low volatility, heat resistance, light resistance, water resistance, good compatibility with vinyl resin, cellulose acetate, cellulose acetylbutyrate, ethyl cellulose, benzyl cellulose, etc., a plasticizer with good plasticizing efficiency ; It is also anti-bacterial without growth of bacteria, non-irritating, flame retardant and degradable; LDG50 rats orally >7 mL/(kg body weight), cats> 3.5 mL/ (kg body weight), use 10% The rats fed by TBC had no abnormal organs after 8 weeks. TBC does not dissolve in the animal body but is excreted from the body. It has no effect on humans and is safe. TBC quality is divided into high-quality products and first-class products. The indicators are: appearance colorless transparent liquid, nearly colorless transparent liquid; color (iodine colorimetric) ≤50; acidity (calculated as citric acid mg KOH/g) ≤0·015; water content ≤0.3; content ≥99·7%; d2041·037~1·047.

Isomerism

Chemically, butanol has four isomers—n-butanol, isobutanol, sec-butanol, and tert-butanol. The corresponding tributyl citrate has four isomers—three citrates. N-butyl ester, triisobutyl citrate, tri-sec-butyl citrate and tri-tert-butyl citrate. Industrially, the most excellent plasticizer is tri-n-butyl citrate, followed by tri-isobutyl citrate, and tri-sec-butyl citrate is rarely seen.

Citrate as metabolite

Citrate and iso-citrate are intermediates in the tricarboxylic acid (TCA) cycle in mitochondria and bacteria. In mitochondria, citrate synthase produces citrate from oxaloacetate (OAA) and acetyl-CoA. Citrate can be transported from mitochondria to cytosol by citrate carrier (CIC) to restore OAA and acetyl-CoA. Acetyl-CoA can be used for synthesis of fatty acids and for histone acetylation. OAA can be converted into pyruvate or lactate. Citrate inhibits glycolysis and TCA cycle, and stimulates gluconeogenesis and lipid synthesis. During inflammation, activated macrophages downregulate TCA cycle and direct citrate from ATP production into cytosol for production of prostaglandin and, via NADPH, production of NO and reactive oxygen species. In cancer cells, CIC is upregulated and citrate is directed from mitochondria to cytosol for anabolic processes.

Citrate as chelating agent

Citrate is a chelating agent for di- and trivalent metal ions (Me²⁺, Me³⁺). Sodium citrate is used as blood anticoagulant in processing of blood sampling and during haemofiltration and haemodialysis, because citrate chelates Ca²⁺ which is an essential component in blood clotting cascade. The risk of hypocalcaenemia and hypomagnesaemia is low, because citrate is metabolized in the kidneys, the liver, and skeletal muscle, and calcium and magnesium are subsequently released back into the circulation. In renal tubular fluid and urine citrate keeps Ca²⁺ in soluble form, preventing it from crystallization as calcium oxalate and phosphate and forming kidney stones. Calcium sensing receptor (CaSR) in tubular system regulates citrate transport via dicarboxylate transporter NaDC1 from tubular fluid.

Reference

1. Iacobazzi V.; et al. Citrate - new functions for an old metabolite. Biol Chem. 2014; 395(4): 387-399.