Taurine: new implications for an old amino acid.

Taurine is a semi-essential amino acid and is not incorporated into proteins. In mammalian tissues, taurine is ubiquitous and is the most abundant free amino acid in the heart, retina, skeletal muscle, brain, and leukocytes. In fact, taurine reaches up to 50 mM concentration in leukocytes. Taurine has been shown to be tissue-protective in many models of oxidant-induced injury. One possibility is that taurine reacts with hypochlorous acid, produced by the myeloperoxidase pathway, to produce the more stable but less toxic taurine chloramine (Tau-Cl). However, data from several laboratories demonstrate that Tau-Cl is a powerful regulator of inflammation. Specifically, Tau-Cl has been shown to down-regulate the production of pro-inflammatory mediators in both rodent and human leukocytes. Taurolidine, a derivative of taurine, is commonly used in Europe as an adjunctive therapy for various infections as well as for tumor therapy. Recent molecular studies on the function of taurine provide evidence that taurine is a constituent of biologic macromolecules. Specifically, two novel taurine-containing modified uridines have been found in both human and bovine mitochondria. Studies investigating the mechanism of action of Tau-Cl have shown that it inhibits the activation of NF-kappaB, a potent signal transducer for inflammatory cytokines, by oxidation of IkappaB-alpha at Met45. Key enzymes for taurine biosynthesis have recently been cloned. Cysteine sulfinic acid decarboxylase, a rate-limiting enzyme for taurine biosynthesis, has been cloned and sequenced in the mouse, rat and human. Another key enzyme for cysteine metabolism, cysteine dioxygenase (CDO), has also been cloned from rat liver. CDO has a critical role in determining the flux of cysteine between cysteine catabolism/taurine synthesis and glutathione synthesis. Taurine transporter knockout mice show reduced taurine, reduced fertility, and loss of vision due to severe apoptotic retinal degeneration. Apoptosis induced by amino chloramines is a current and important finding since oxidants derived from leukocytes play a key role in killing pathogens. The fundamental importance of taurine in adaptive and acquired immunity will be unveiled using genetic manipulation.