Abstract: The contribution of cystathionine gamma-lyase, cystathionine beta-synthase and cysteine aminotransferase coupled to 3-mercaptopyruvate sulphurtransferase to cysteine desulphhydration in rat liver and kidney was assessed with four different assay systems. Cystathionine gamma-lyase and cystathionine beta-synthase were active when homogenates were incubated with 280 mM-L-cysteine and 3 mM-pyridoxal 5'-phosphate at pH 7.8. Cysteine aminotransferase in combination with 3-mercaptopyruvate sulphurtransferase catalysed essentially all of the H2S production from cysteine at pH 9.7 with 160 mM-L-cysteine, 2 mM-pyridoxal 5'-phosphate, 3 mM-2-oxoglutarate and 3 mM-dithiothreitol. At more-physiological concentrations of cysteine (2 mM) cystathionine gamma-lyase and cystathionine beta-synthase both appeared to be active in cysteine desulphhydration, whereas the aminotransferase pathway did not. The effect of inhibition of cystathionine gamma-lyase by a suicide inactivator, propargylglycine, in the intact rat was also investigated; there was no significant effect of propargylglycine administration on the urinary excretion of total 35S, 35SO4(2-) or [35S]taurine formed from labelled dietary cysteine.

Abstract: Taurine neurons in the cerebellum of rabbit, rat, and mouse were localized at the light microscope level by using polyclonal antibodies against cysteine sulfinic acid decarboxylase (CSADCase; EC 4.1.1.29), the enzyme responsible for the conversion of cysteine sulfinic acid to hypotaurine and of cysteic acid to taurine. The indirect peroxidase-antiperoxidase method was used on Vibratome sections and on serial sections of paraffin-embedded tissue. Intensification of CSADCase immunoreactivity was achieved by pretreatment of the animal with L-cysteine or L-cysteic acid intravenously 1-2 hr prior to perfusion. A combination of L-cysteic acid and demecolcine, which retards axoplasmic flow, was most effective in maximizing CSADCase immunoreactivity. Although these treatments intensified immunoreactivity in neurons, no more cells were reactive than in untreated controls. L-Glutamic acid did not increase CSADCase immunoreactivity but did increase immunoreactivity with antibodies against L-glutamic acid decarboxylase (GAD; EC 4.1.1.15), the synthetic enzyme for γ-aminobutyric acid. Specificity was established by negative results obtained with various control incubations including the use of CSADCase antiserum preabsorbed with the antigen. Taurine neurons of the cerebellar cortex are arranged in sagittal microbands, defined by intensely CSADCase-reactive Purkinje neurons and their axons and dendrites, together with stellate, basket, and Golgi cells and their processes. In the vermis there is a narrow midline band, flanked laterally by three wider bands on either side, each separated from the next by an unreactive zone. Although the zonal borders are sharp, the interzonal areas contain some CSADCase-immunoreactive axons but no cell bodies. The seven vermal bands are best observed in the anterior lobe. Others exist in the lateral hemispheres. The paraflocculus and flocculus contain numerous intensely immunoreactive neurons, and banding is difficult to discern. Lobule X of the vermis is also heavily endowed with taurine neurons. Numerous large and medium-sized deep cerebellar and vestibular nuclei are also immunoreactive. These observations indicate that cerebellar neurons are chemically heterogeneous but that neurons of similar chemical signature in the cerebellar cortex are organized into sagittal microbands. This corroborates our earlier evidence that Purkinje cells containing motilin and those containing both motilin and γ-aminobutyric acid are also arranged in vermal sagittal microbands. The midline vermal band contains Purkinje neurons with multiple neuroactive substances—taurine, γ-aminobutyric acid, and motilin. It remains to be determined how this chemical zonation in the cerebellar cortex relates to the banded afferent innervation from spinal, vestibular, reticular, and olivary sources.

Abstract: I Physicochemical Properties of Taurine: Introduction.- Coordination and Binding of Taurine as Determined by Nuclear Magnetic Resonance Measurements on 13C-Labeled Taurine.- II Taurine in Nutrition and Development: Introduction.- Sources and Turnover Rates of Taurine in Newborn, Weanling, and Mature Rats.- Studies on the Renal Handling of Taurine: Changes During Maturation and After Altered Dietary Intake.- Taurine and Tapetum Structure.- Taurine Deficiency: A Rationale for Taurine Depletion.- Taurine Nutrition in Man.- III Transport and Metabolism of Taurine: Introduction.- Hypotaurine Aminotransferase.- Hypotaurine Uptake in Mouse Brain Slices.- The Sulfur-Containing Amino Acid Pathway in Normal and Malignant Cell Growth.- Taurine Transport by Reconstituted Membrane Vesicles.- IV Taurine and the Heart: Introduction.- Electrophysiological Effects of Taurine in Cardiac Purkinje Fibers and Myocardial Taurine Loss during Ischemia. Is There a Relationship?.- Observations on the Action of Taurine at Arterial and Cardiac Levels.- Elevated Blood Taurine Levels After Myocardial Infarction or Cardiovascular Surgery: Is There any Significance?.- V The Neurochemistry of Taurine: Introduction.- Interaction of Taurine with Its Precursor, Cysteine Sulfinic Acid, in the Central , Nervous System.- Differential Effects of Light and Dark Adaptations on Function and Metabolism of Retinal Taurine and ?-Aminobutyric Acid (GABA).- Changed Taurine-Glutamic Acid Content and Altered Nervous Tissue Cytoarchitecture.- Taurine, Cysteinesulfinic Acid Decarboxylase and Glutamic Acid in Brain.- VI The Neuropharmacology of Taurine: Introduction.- The Role of Taurine in Nervous Tissue, Its Effects on Ionic Fluxes.- Taurine Receptors in CNS Membranes: Binding Studies.- Specific Binding of Taurine in Central Nervous System.- Central Neuropharmacology of D-Ala2-Met-Enkephalinamide and its Interactions with Taurine in Rats.- Central Effects of Taurine: Antagonistic Effects on Central Actions of Angiotensin.- Taurine and Thermoregulation: Behavioral and Cellular Studies.- Influence of Centrally Administered Taurine on Thermoregulation and Fever.- Taurine and Friedreich's Ataxia: An Update.- Discussions on Taurine: Introduction.- Session I: How are Tissue Taurine Concentrations Regulated?.- Session II: Are the Pharmacological Actions of Taurine Related to its Physiological Functions?.- Session III: What Does Taurine Do?.- Session IV: Do Taurine and Its Analogs or Cogeners Have Actions in Common?.- Session V: Is Taurine Essential in Development?.- Session VI: Does Taurine Have Clinical Significance?.- List of Participants.

Abstract: L-Cysteic and cysteine sulfinic acids decarboxylase (CADCase/CSADCase) and L-glutamic acid decarboxylase (GADCase), the synthetic enzymes for taurine and gamma-aminobutyric acid, respectively, have been purified to homogeneity from bovine brain. Although CADCase/CSADCase and GADCase copurified through various column procedures, these two enzymes can be clearly separated by a hydroxyapatite column. The purification procedures involve ammonium sulfate fractionation, column chromatographies on Sephadex G-200, hydroxyapatite, DEAE-cellulose, and preparative polyacrylamide gel electrophoresis. The Km values for CADCase/CSADCase are 0.22 and 0.18 mM with L-cysteic and cysteine sulfinic acids as substrates, respectively. CADCase/CSADCase cannot use L-glutamate as substrate. GADCase can use L-glutamate, L-cysteic, and cysteine sulfinic acid as substrates with Km values of 1.6, 5.4, and 5.2 mM, respectively. Antibodies against CADCase/CSADCase do not crossreact with GADCase preparations and vice versa. It is concluded that CADCase/CSADCase and GADCase are two distinct enzyme entities and they are responsible for the biosynthesis of taurine and gamma-aminobutyric acid, respectively.

Abstract: A gram-positive, anaerobic, chain-forming, rod-shaped anaerobe (isolate G20-7) was isolated from normal human feces. This organism was identified by cellular morphology as well as fermentative and biochemical data as Eubacterium aerofaciens. When isolate G20-7 was grown in the presence of Bacteroides fragilis or Escherichia coli (or another 7 alpha-hydroxysteroid dehydrogenase producer) and chenodeoxycholic acid, ursodeoxycholic acid produced. Time course curves revealed that 3 alpha-hydroxy-7-keto-5 beta-cholanoic acid produced by B. fragilis or E. coli or introduced into the medium as a pure substance was reduced by G20-7 specifically to ursodeoxycholic acid. The addition of glycine- and taurine-conjugated primary bile acids (chenodeoxycholic and cholic acids) and other bile acids to binary cultures of B. fragilis and G20-7 revealed that (i) both conjugates were hydrolyzed to give free bile acids, (ii) ursocholic acid (3 alpha, 7 beta, 12 alpha-trihydroxy-5 beta-cholanoic acid) was produced when conjugated (or free) cholic acid was the substrate, and (iii) the epimerization reaction was at least partially reversible. Corroborating these observations, an NADP-dependent 7 beta-hydroxysteroid dehydrogenase (reacting specifically with 7 beta-OH-groups) was demonstrated in cell-free preparations of isolate G20-7; production of the enzyme was optimal at between 12 and 18 h of growth. This enzyme, when measured in the oxidative direction, was active with ursodeoxycholic acid, ursocholic acid, and the taurine conjugate of ursodeoxycholic acid (but not with chenodeoxycholic, deoxycholic, or cholic acids) and displayed an optimal pH range of 9.8 to 10.2

Abstract: Amino acid concentrations have been determined in rat brain regions (cortex, striatum, cerebellum, and hippocampus) by HPLC after administration of acute anticonvulsant doses of sodium valproate (400 mg/kg, i.p.) and γ-vinyl-GABA (1g/kg, i.p.). After valproate administration the GABA level increases only in the cortex; aspartic acid concentration decreases in the cortex and hippocampus, and glutamic acid decreases in the hippocampus and striatum and increases in the cortex and cerebellum. There are no changes in the concentrations of glutamine, taurine, glycine, serine, and alanine following valproate administration. Only the GABA level increases in all the regions after γ-vinyl-GABA administration. Cortical analyses 2, 4 and 10 minutes after pulse labeling with 2-[14C]glucose, i.v., shown no change in the rate of cortical glucose utilization in the valproate treated group. The rate of labeling of glutamic acid is also unchanged, but the rate of labeling of GABA is reduced following valproate administration. After γ-vinyl-GABA administration there is no change in the rate of labeling of GABA. These biochemical findings can be interpreted in terms of a primary anticonvulsant action of valproate on membrane receptors with secondary effects on the metabolism of amino acid neurotransmitters. This contrasts with the primary action of γ-vinyl-GABA on GABA-transaminase activity.

Abstract: Male, Sprague-Dawley rats were fed L-amino acid diets that contained 0.4% L methionine and either 0, 0.2% (control), or 2.6% L-cysteine (free base) for 5 or 20 days. Hepatic cysteine dioxygenase activity in rats fed 2.6% cysteine was 5 and 3-times as great as in pair-fed control rats at 5 and 20 days, respectively. Cysteine sulfinate decarboxylase activity in liver of rats fed 2.6% cysteine for 20 days was about 40% of the pair-fed control level. The activity of cysteine sulfinate aminotransferase and the rate of cysteine desulfhydration were not influenced by dietary cysteine content. Rats that had been fed these diets for 5 days were intubated with 5 g of diet that contained either 0.2% or 2.6% L-[35S] cysteine. The 24-hour urinary excretion of total 35S, 35SO4, and [35S] taurine by rats that had been fed 2.6% cysteine for 5 days and intubated with 0.2% L[35S] cysteine was 1.4-, 1.8-, and 2.4-fold, respectively, that of pair-fed control rats. About 2.1, 1.8, and 9.1 times as much 35S, 35SO4, and [35S] taurine, respectively, were excreted by rats fed 2.6% cysteine for 5 days and intubated with 2.6% L-[35S] cysteine as was excreted by pair-fed control rats. Urinary excretion of these metabolites was not different between rats fed 0 and 0.2% cysteine. These results indicate that the cysteine sulfinate pathway plays a major regulatory role in the metabolism of excess cysteine.

Abstract: When introduced intracerebroventricularly, quinolinic acid appeared to be the only kynurenine metabolite among those tested (L- and DL-kynurenine sulfate, kynurenic and nicotinic acids, nicotinamide) which induced locomotor excitement and clonic scizures in rats; in high dosage all exhibited convulsant action in mice. L-Kynurenine sulfate (500μg) induced continuous rotation in rats around a longitudinal axis in one or other direction. It also potentiated the convulsant effect of strychnine sulfate and caffeine. Neither the excitatory amino acids, L-glutamic and L-aspartic acids nor the inhibitory amino acids, GABA, glycine and taurine induced excitement or scizures in rats but did in mice. In rats, GABA, glycine and taurine induced sedation, side position and discoordination. The convulsants, strychnine sulfate and pentylenetetrazole, induced scizures both in rats and mice. Differences between species may derive from the better access of intracerebroventricularly administered drugs to mouse hippocampus. Thus mice may be preferable for studies of this type on excitatory amino acids (including kynurenine pathway metabolites) and rats for those on inhibitory amino acids.

Abstract: Pretreatment of rats with homotaurine (3 aminopropanesulfonic acid; 3APS), a synthetic γ-aminobutyric acid (GABA) analog, protected from the convulsant and cytotoxic action of systemically injected kainic acid (KA). Wet dog shaking (WDS) behavior was significantly reduced. Taurine, an inhibitory non-GABA-mimetic amino acid, and muscimol (another direct GABA-agonist) reduced the number of seizures and lesions in the brain but were less effective than homotaurine. Progabide (a GABA-agonist) did not modify kainic acid effects. The neurotoxicity of kainic acid could have been due to repetitive convulsive activity. Activation of GABA-mediated inhibition is an effective, but not the determinant means of preventing KA-induced abnormalities.

Abstract: The effects of nicotine on brain protein metabolism and on the properties of the nicotine binding site were investigated in newborn animals exposed to nicotine during gestation. Brain protein synthesis rates measured in vivo were lower by 18% in newborn of treated animals. Protein degradation rates measured in vitro in the presence of nicotine were lower by 13%. The effect was specific forl-(-) nicotine, sinced-(+)nicotine, nicotinic acid, or nicotinamide had no effect on degradation rates. Newborn brain amino acid levels, mainly nonessential amino acids and amino acids of putative neurotrans nitter function, were changed some-what; an increase in the level of taurine (13%), threonine (21%), serine (35%) and glycine (35%), and a decrease in lysine (14%) was observed in the offspring of nicotine treated animals (0.5 mg/kg, s.c., 2×daily throughout gestation). These changes could not account for the decrease in protein metabolism. Nicotine binding was higher by 25% in the offspring of animals exposed to nicotine during gestation. No such increase was found after treatment of adult rats with nicotine, indicating that the properties of the nicotine binding site change with age.

Abstract: The relative contribution of diet and biosynthesis to the taurine content of the rat has been determined quantitatively under various dietary conditions. Rats were maintained on diets containing [3H]taurine and/or [35S]methionine of known amounts and specific activities, and subsequently the specific activity of taurine in various tissues was determined. This approach gives a quantitative measure of how much taurine is biosynthesized versus how much is derived from the diet regardless of the biosynthetic route or site of biosynthesis in the animal. With no taurine in the diet, over an 87-day period, 54% of the taurine in the animal had been biosynthesized. This fell to 29% if taurine was present in the diet, and the contribution of dietary taurine to body pools rose to 58%. These changes in biosynthetic contributions were not accompanied by an alteration in the rate of biosynthesis but by an alteration in rate of excretion. When the amounts of biosynthesized taurine appearing in the urine over 63 days was added to the amounts found in the carcass, 3.1 mmol were found to be biosynthesized by animals receiving taurine in the diet as compared to 2.9 mmol in animals on a taurine-deficient diet. In any one experiment, the contribution of diet or biosynthesis is invariant from tissue to tissue indicating that the rate of exchange of taurine between tissues is faster than the rate of elimination of taurine from the body.

Abstract: Isolated frog rod outer segments (ROS) with a leaky plasma membrane showed a bicarbonate-dependent, ATP-activated45Ca accumulation. This calcium uptake requires magnesium and is specific for ATP; Other nucleotides, ITP, GTP, UTP and the non-hydrolysable analogue of ATP β-γ-methylene ATP did not substitute for ATP.45Ca accumulation was inhibited by mersalyl, ethylmaleimide, ruthenium red, oligomycin and dicyclohexylcarbodiimide and was unaffected by ouabain. Addition of taurine to the incubation medium enhanced45Ca uptake in a concentration-dependent manner; increases of more than 100% being produced by 25 mM taurine. The taurine-induced stimulation of45Ca uptake was also sensitive to the tested inhibitors. The effect of taurine was only exerted on the bicarbonate-dependent, ATP-activated45Ca uptake. Calcium accumulation observed in the absence of ATP or in a tris-buffered medium was unaffected by taurine. Other amino acids, glycine, GABA, β-alanine, glutamic acid and the taurine analogue guanidinoethyl-sulfonate did not stimulate45Ca uptake. These results suggest that taurine is affecting a Mg-ATPase activity responsible for calcium accumulation in frog ROS.

Abstract: 1. The unidirectional influx of amino acids into the guinea-pig syncytiotrophoblast was measured using a single circulation paired-tracer dilution technique which allows separate characterization of both fetal and maternal interfaces. An in situ preparation perfused through the fetal circulation was used to examine the fetal side, while an isolated preparation perfused through both the fetal and maternal circulations was used to study both interfaces simultaneously. 2. On the fetal side the maximal uptake (Umax) determined at tracer concentrations was high for the short-chain neutral amino acid alanine (76%) and the long-chain neutrals, leucine (75%), phenylalanine (90%) and tyrosine (82%) and for the basic amino acid lysine (65%). In contrast, Umax was negligible for α-methylaminoisobutyric acid and taurine, a β-amino acid. 3. The uptake of alanine and phenylalanine on the fetal side was inhibited by both short-chain (alanine, serine, cysteine) and long-chain (phenylalanine, methionine, leucine) neutral amino acids. d-alanine had no effect on l-alanine uptake whereas d-phenylalanine significantly inhibited that of l-phenylalanine. Diaminobutyric acid, lysine and arginine were effective inhibitors of alanine uptake but had no effect on phenylalanine uptake. 4. On the maternal side uptake of alanine, phenylalanine and lysine was measured. Over a wide range of concentrations self-inhibition of alanine influx was similar to the cross-inhibition observed with phenylalanine. In contrast, the influx of phenylalanine, which was strongly self-inhibited, was only partially cross-inhibited by alanine. 5. Influx of alanine and phenylalanine was measured at various perfusate concentrations and was found to be saturable on both maternal and fetal sides. The data were fitted to a single hyperbola and, on the maternal side, the Km for alanine (10.3±2.7 m m, mean± s.e., n = 3) was three-fold higher than the value measured for phenylalanine (3·1±0·8 m m). On the fetal side the Km values for alanine (8·4±1·4 m m, n = 4) and phenylalanine (11·9±1·9 m m, n = 3) were similar. 6. The uptake of alanine, phenylalanine and lysine appeared to be highly sodium-dependent accounting for 40-70% of the total influx. However, the inhibited fractions were found to be different on the two sides of the placenta. 7. The results of uptake, cross-inhibition and Na+-dependency experiments suggest the presence of an alanine-serine-cysteine (ASC) type system and a leucine (L) type system with markedly overlapping specificities at both the fetal and maternal interfaces. Separate kinetic characterization of a two carrier system was not possible under the conditions of these experiments. However, kinetic parameters for the over-all transport of alanine and phenylalanine were measured.

Abstract: A series of 6- and 8-(aminomethyl)-4H-1,2,4-benzothiadiazine 1,1-dioxides has been synthesized and tested for interaction with various GABA systems. None of the compounds showed significant GABA-mimetic properties, but unexpectedly, compound 7 [6-(aminomethyl)-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide] possessed the properties of a selective antagonist of taurine, as measured by the antagonism of taurine-induced inhibition of rat cerebellar Purkinje firing.

Abstract: Free amino acids (FAA) and creatine contents of white and dark muscles of yellowtail (Seriola quinqueradiata) were measured and compared during ice storage. White muscle contained a large quantity of free histidine (1,160 mg/100g), while an equally large amount of taurine (1,150 mg/100g) was present in the dark muscle. Little change in the levels of most FAA occurred in the white muscle during ice storage for over 40 days but in the dark muscle the levels of almost all FAA except taurine increased significantly over a period of 33 days. Creatine was present in higher concentration in the white than in the dark muscle (510 vs 170 mg/100g), while its level did not change in either muscle during the entire storage period.

Abstract: The introduction of 75Se-homocholic acid taurine (75SeHCAT) greatly facilitates the investigation of diarrhoea of unknown origin. By using gamma-labelled bile acids, daily faecal bile acid loss can be measured in total collected stools, thus circumventing laborious mixing and sampling. The 75SeHCAT method proved to be reliable for the determination of bile acid turnover, giving results identical to the established turnover method using 14C-taurocholic acid. The new method however, is simpler and faster.

Abstract: The quantitative importance of diet versus biosynthesis as sources of taurine has been established in mice receiving dietary levels of 0.062% [3H]taurine and 0.74% [35S]methionine as sole sulfur-containing amino acids. After 15 days on diets radiolabeled with these levels of taurine and methionine, 16% of total-body taurine had been derived from diet and 24% from biosynthesis. By 30 days, these contributions had risen to 29% and 33%, respectively, and by 61 days to 46%. The half-life of turnover of taurine in the mouse was 18.6 days. These findings indicate that, like the rat and guinea pig, but unlike the cat and human, the mouse exhibits considerable biosynthetic capacity for taurine.

Abstract: The biliary metabolites from normal rats dosed with either pharmacological or physiological doses of all-trans-[11,12-3H2]retinoic acid were investigated. Biliary metabolites excreted during the first 24 h account for approximately 60-65% of the radiolabeled dose. A major polar metabolite was purified to homogeneity by using Sephadex LH-20 chromatography and several high-performance liquid chromatographic procedures. This metabolite was negatively charged as revealed by high-performance liquid chromatography on ion-exchange columns and accounts for 10% of the total biliary radioactivity (6% of the dose). The polar compound was positively identified by using Fourier transform proton nuclear magnetic resonance spectroscopy, high- and low-resolution mass spectrometry, fast atom bombardment mass spectrometry, ultraviolet absorption spectrophotometry, Fourier transform infrared spectroscopy, amino acid analysis, and chemical derivatization as 2-[8-[6-(hydroxymethyl)-2,6-dimethyl-3-oxo-1-cyclohexen-1-yl]-2,6- dimethyl-5,7-octadienamido]ethanesulfonic acid. The metabolic transformations required for the generation of this metabolite from all-trans-retinoic acid are the following: (1) allylic oxidation at carbon 4 of the cyclohexene ring to produce a 4-keto group, (2) hydroxylation of one of the methyl groups at carbon 1 of the cyclohexene ring, (3) saturation of the two terminal double bonds in the side chain, (4) loss of the terminal carboxyl group of the side chain via decarboxylation, and (5) conjugation of the resulting retinoid with taurine. To our knowledge, this metabolite represents the first taurine conjugate of a fat-soluble vitamin to be identified.