Citrate

The citrate anion

A citrate can refer either to the conjugate base of citric acid, (C₃H₅O(COO)₃³⁻), or to the esters of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.

Other citric acid ions

Since citric acid is a multifunctional acid, intermediate ions exist, hydrogen citrate ion, HC₆H₅O₇²⁻ and dihydrogen citrate ion, H₂C₆H₅O₇⁻. These may form salts as well, called acid salts.

Acidity

Salts of the hydrogen citrate ions are weakly acidic, while salts of the citrate ion itself (with an inert cation such as sodium ion) are weakly basic.

Buffering

As a weak acid, citrate can be used as a component in buffer solutions, including the commonly used SSC 20X hybridization buffer.^[1] This buffer uses sodium citrate and sodium chloride to maintain a neutral 7.0 pH. Other buffers may use a mixture of sodium citrate and citric acid – canonical buffer tables compiled for biochemical studies^[2] describe solutions of citrate and acid for buffer pHs of between 3.0 and 6.2.

Chelating

Citric acid can act as a mild chelating agent; citrate, usually in the form of trisodium citrate, may be given as an anticoagulant, because it chelates calcium ions, and therefore inhibits coagulation. Another application is in the form of iron(II) citrate as a nutritional supplement. Here, the benefit is the solubility as a chelate of the otherwise mostly insoluble iron.

Metabolism

Main article: TCA cycle

Citrate is an intermediate in the TCA (Krebs) cycle. After the pyruvate dehydrogenase complex forms acetyl-CoA, from pyruvate and five cofactors (thiamine pyrophosphate, lipoamide, FAD, NAD⁺, and CoA), citrate synthase catalyzes the condensation of oxaloacetate with acetyl CoA to form citrate. Citrate continues in the TCA cycle via aconitase with the eventual regeneration of oxaloacetate, which can combine with another molecule of acetyl CoA and continue cycling.

Fatty acid synthesis

Citrate can also be transported out of the mitochondria and into the cytoplasm, then broken down into acetyl-CoA for fatty acid synthesis. 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 to the cytoplasm, converted to acetyl CoA, which is converted into malonyl CoA by the acetyl CoA carboxylase, which is allosterically modulated by citrate.

See also TCA cycle

Role in glycolysis

High concentrations of cytosolic citrate can inhibit phosphofructokinase, catalyst of one of the rate-limiting steps of glycolysis.

References

1. ^ Maniatis et al., 1982.^{[clarification needed]}
2. ^ G. Gomori, Preparation of buffers for use in enzyme studies, 1955.