Taurine Biosynthesis by Neurons and Astrocytes

Abstract

The physiological roles of taurine, a product of cysteine degradation and one of the most abundant amino acids in the body, remain elusive. Taurine deficiency leads to heart dysfunction, brain development abnormalities, retinal degradation, and other pathologies. The taurine synthetic pathway is proposed to be incomplete in astrocytes and neurons, and metabolic cooperation between these cell types is reportedly needed to complete the pathway. In this study, we analyzed taurine synthesis capability as reported by incorporation of radioactivity from [ 35 S]cysteine into taurine, in primary murine astrocytes and neurons, and in several transformed cell lines (human (SH-SY5Y) and murine (N1E-115) neuroblastoma, human astrocytoma (U-87MG and 1321 N1), and rat glioma (C6)). Extensive incorporation of radioactivity from [35 S]cysteine into taurine was observed in rat glioma cells as well as in primary mouse astrocytes and neurons, establishing the presence of an intact taurine synthesis pathway in these cells. Interestingly, exposure of cells to cysteine or cysteamine resulted in elevated intracellular hypotaurine without a corresponding increase in taurine levels, suggesting that oxidation of hypotaurine limits taurine synthesis in cells. Consistent with its role as an organic osmolyte, taurine synthesis was stimulated under hypertonic conditions in neurons.Taurine, or ethanesulfonic acid, is one of the most abundant amino acids in the body whose physiological role remains elusive. Its biosynthesis involves the sequential oxidation of cysteine to cysteinesulfinic acid, catalyzed by cysteine dioxygenase, decarboxylation by cysteinesulfinate decarboxylase, and oxidation of the resulting hypotaurine to taurine by a putative hypotaurine dehydrogenase (Fig. 1). The latter enzyme has, however, not been purified to homogeneity and remains uncharacterized (1-3). In fact, it has been suggested that oxidation of hypotaurine to taurine might occur via a nonenzymatic reaction in cells (4 -6). Hypotaurine can also be produced via oxidation of cysteamine, the end product of coenzyme A degradation (Fig. 1). Cysteamine oxidation is catalyzed by 2-aminoethanethiol dioxygenase, which is widely expressed in mammalian tissues (7).Although it is generally believed that taurine cannot be further metabolized and is excreted by the kidney or as a bile component, there are several older reports in the literature on the conversion of taurine to isethionic acid in mammalian tissues (8 -11). Various roles have been ascribed to taurine, including regulation of osmotic pressure (12-14), neuromodulatory (3, 15) and immunomodulatory (16) factors, and as an antioxidant for detoxifying hypochlorous acid, forming taurine chloramine (12). Taurine deficiency is associated with heart dysfunction, brain development abnormalities, retinal degradation, and other pathologies (3, 17). Taurine is actively transported into cells by a specific Na ϩ -dependent transporter (TAUT) and accumulates to high concentrations particularly in the liver, muscle, and retina. ...

Severity of experimental traumatic brain injury modulates changes in concentrations of cerebral free amino acids

“…It has been indicated that both compounds, besides various still debated biological functions 51, 52, 53, 54, 55, play a determining contribution in controlling cerebral osmolarity 52, 55, 56. Even though some studies showed a decrease in Tau after TBI 57, 58, 59, our results are in line with those reported by others 60, 61 and are logically connected to dysfunctional NAA homeostasis following sTBI and to a precise role of osmolite regulator performed by cerebral Tau.…”

Requirement for the Mitochondrial Pyruvate Carrier in Mammalian Development Revealed by a Hypomorphic Allelic Series

“…8B). Hypotaurine, an amino acid derivative that may function as a neurotransmitter or an antioxidant in addition to its role in osmolyte balance (37,38), was the most dramatically upregulated metabolite in the Mpc1 KI/KI brain at more than 15 times the concentration in the WT brain (Fig. 8B).…”

Difference between Plasma Concentrations of Three Amino Acids in Patients with Ischemic and Hemorrhagic Stroke

“…Moreover, taurine deficiency is associated with various pathologies including heart dysfunction [31], abnormalities of brain development [32], and cardiomyopathy [33]. In the astrocytes and the neurons, taurine is the principal osmolyte which during hypotonic or hypertonic conditions it goes out from or accumulates inside the cell, respectively [12]. Melani and colleagues used the brain microdialysis technique and demonstrated that after middle cerebral artery occlusion in the rat taurine was increased in the dialysate samples [34].…”

“…Taurine is also one of the most abundant free amino acids in the heart, brain, liver, retina and skeletal muscles [12]. Taurine is also the second most abundant amino acid in the brain after glutamate [13].…”

“…Taurine or 2-ethane sulfonic acid is the semi-essential amino acid, not incorporated in the synthesis of protein and is the principal intracellular free β-amino acid [12]. Taurine is also one of the most abundant free amino acids in the heart, brain, liver, retina and skeletal muscles [12].…”