Abstract: Animals fed diets lacking the amino acid taurine have low plasma and tissue levels of taurine and ultimately have retinal dysfunction. Since parenteral nutrition does not ordinarily provide taurine, we looked for evidence of taurine deficiency in 21 children and 23 adults undergoing long-term parenteral nutrition at home for an average of 27 +/- 23 (S.D.) months. The fasting plasma taurine level was reduced in children as compared with controls (26 +/- 13 vs. 57 +/- 16 mumol per liter, P less than 0.001). In adults with less than 25 per cent intestinal absorption of the recommended caloric intake, the plasma taurine level was also significantly reduced and correlated inversely with the duration of parenteral nutrition. Electroretinograms were abnormal in each of eight children who were examined. Addition of taurine to the intravenous solutions restored plasma levels to normal in four children; the electroretinograms of three of these children also became normal. The plasma taurine level became abnormally low again in two of three children one year after the intravenous taurine was discontinued. We conclude that children and possibly adults receiving long-term parenteral nutrition have a nutritional requirement for taurine.

Abstract: We describe neurochemical abnormalities found in the brains of 2 patients with autopsy-confirmed Hallervorden-Spatz (HS) disease. In 1 patient, contents of cystine and of glutathione-cysteine mixed disulfide in the globus pallidus were markedly elevated above values for appropriate control subjects. Activity of cysteine dioxygenase, which converts cysteine to cysteine sulfinic acid, was reduced in the globus pallidus, but normal in the frontal cortex and putamen of both patients. gamma-Aminobutyric acid content was markedly decreased in the globus pallidus and substantia nigra of both patients. These results suggest that cysteine accumulates locally in the globus pallidus in Hallervorden-Spatz disease as a result of an enzymatic block in the metabolic pathway from cysteine to taurine. Accumulated cysteine may chelate iron, accounting for the local increase in iron content in Hallervorden-Spatz disease. The combined excess of cysteine and ferrous iron may generate free radicals that damage neuronal membranes to cause the typical morphological changes observed in this disorder.

Abstract: More than simply cataloging the numerous experimental models in which taurine plays a modulating role, this discussion aims at stimulating further investigation of the potential clinical value of this abundant sulfur amino acid. Both the biomedical investigator and clinician must be struck by the enormous amount of taurine floating freely in the intracellular water of the cells. In cardiac tissue alone, taurine levels of 20 mM or higher may be found.2, 3 Given this abundance of taurine, why is our understanding of its function so elusive? Although it is clear taurine is important in conjugating bile acids to form water-soluble bile salts, only a fraction of available taurine is used for this function, predominantly in young animals and children. While taurine conjugation is the preferred route of bile acid conjugation in the young, changes in adults given 250 mg of taurine daily for two to three weeks are insignificant. Total pool size of bile acid and chenodeoxycholic acid declines. Unchanged are the rate of bile acid synthesis or the secretion rates of biliary cholesterol, bile acid and phospholipids. Biliary cholesterol saturation also stays the same.152 The finding that taurine availability protects against cholestasis induced by monohydroxy bile acids remains confined to guinea pigs.153 The abundance of taurine suggests it may be an osmoregulator of cell volume, and there is convincing evidence that it serves this function in fish. Taurine may play this role in the brain under high osmotic states such as hypernatremia, dehydration and uremia. Evidence is strong that taurine is vital in maintaining retinal function, which may explain why taurine is so abundant in human breast milk. Prolonged TPN feeding of infants demonstrates the importance of taurine in retinal development. We have begun to appreciate the role of the kidney in conserving taurine and how this is perturbed in the neonatal period. Taurine has recently been added to infant formulas (about 50 mg/L). Cataloging what we know of taurine function, however, produces a list of “maybes.” Now is the time for exhaustive, careful taurine research that will produce more definite answers.

Abstract: Compared to healthy controls, unmedicated schizophrenic patients had significantly higher plasma concentrations of taurine, methionine, valine, isoleucine, leucine, phenylalanine, and lysine. Except for taurine, these amino acids share the L-transport system for neutral amino acids. In the patients, homovanillic (HVA) acid levels in CSF were decreased and the plasma levels of the amino acids competing with tyrosine and tryptophan for transport into the brain, were all negatively correlated to the CSF concentrations of HVA and 5-HIAA. These findings could be explained by a change in the affinity of the L-system or by a decrease in its overall capacity in schizophrenia. Raised plasma levels of the competing amino acids may limit the brain uptake of tyrosine, leading to a diminished dopamine turnover, and resulting in a compensatory development of supersensitive dopamine receptors.

Abstract: In a double-blind, randomized, crossover, placebo-controlled study, we investigated the effects of adding taurine to the conventional treatment in 14 patients with congestive heart failure for a 4-week period. Compared with placebo, taurine significantly improved the New York Heart Association functional class (p less than 0.02), pulmonary crackles (p less than 0.02), and chest film abnormalities (p less than 0.01). A benefit of taurine over placebo was demonstrated when an overall treatment response for each patient was evaluated on the basis of clinical examination (p less than 0.05). No patient worsened during taurine administration, but four patients did during placebo. Pre-ejection period (corrected for heart rate) decreased from 148 +/- 14 ms before taurine treatment to 137 +/- 12 ms after taurine (p less than 0.001), and the quotient pre-ejection period/left ventricular ejection time decreased from 47 +/- 9 to 42 +/- 8% (p less than 0.001). Side effects did not occur in the patients during taurine. The results indicate that addition of taurine to conventional therapy is safe and effective for the treatment of patients with congestive heart failure.

Abstract: The relationship between activities of enzymes involved in cysteine oxidation and the apparent conversion of cysteine to taurine in vivo were investigated in the rat and cat Both hepatic cysteinesulfinate decarboxylase activity and the oxidation in vivo of cysteine to taurine were lower in the kitten than in the adult female rat and lower in the latter than in the young male rat Our data support the hypothesis that cysteinesulfinate decarboxylase plays a rate-limiting role in taurine biosynthesis

Abstract: The extracellular content of taurine, glutamate, glutamine, and glycine was measured by the novel method of brain dialysis in the acute phases following an intrahippocampal injection of the excitotoxic convulsant brain metabolite quinolinic acid (QUIN). Using bilaterally implanted depth electrodes physically combined with hollow fibers for dialysis, it was possible to collect continuously brain perfusates while simultaneously monitoring brain activity in the unanesthetized rat. In separate animals, hippocampal amino acid tissue levels were measured 2 h after an intracerebral injection of a convulsant dose (156 nmol) of QUIN. When compared with those in animals receiving the nonconvulsant decarboxylation product of QUIN, nicotinic acid, no differences in tissue levels were detected. In contrast, the same dose of QUIN caused a selective increase (2.24-fold) in taurine levels in perfusates from the injected hippocampus. These changes were apparent prior to the onset of electrographic seizures and did not occur in the contralateral hippocampus where seizure activity was equally severe. Thus, increases in extracellular taurine, triggered by the presence of QUIN in the hippocampus, may reflect a selective tissue response to the neurotoxic (rather than the convulsant) effects of this excitotoxin.

Abstract: The effects of taurine on ATP-dependent calcium ion uptake and protein phosphorylation of rat retinal membrane preparations were investigated. Taurine (20 mM) stimulates ATP-dependent calcium ion uptake by twofold in crude retinal homogenates. In contrast, it inhibits the phosphorylation of specific membrane proteins as shown by acrylamide gel electrophoresis and autoradiography. The close structural analogue of taurine, 2-aminoethylhydrogen sulfate, demonstrates similar effects in both systems, i.e., stimulation of ATP-dependent calcium ion uptake and inhibition of protein phosphorylation, whereas isethionic acid and guanidinoethanesulfonate have no effect on either system. A P1 subcellular fraction of the retinal membrane preparation that contains photoreceptor cell synaptosomes has a higher specific activity for the uptake of calcium ions. Phosphorylation of specific proteins in the P1 fraction is also inhibited by the addition of 20 mM taurine. Taurine has no effect on retinal ATPase activities or on phosphatase activity, thus suggesting that it directly affects a kinase system.

Abstract: Rats fed a reduced sulfur amino acid diet (LTD) or a high-taurine diet (HTD) demonstrate a renal adaptive response The LTD results in hypotaurinuria and enhanced brush border membrane vesicle (BBMV) accumulation of taurine The HTD causes hypertaurinuria and reduced BBMV uptake This adaptation may relate to changes in plasma or renal cortex taurine concentration Rats were fed a normal-taurine diet (NTD), LTD, or HTD for 14 d or they underwent: (a) 3% beta-alanine for the last 8 d of each diet; (b) 3 d of fasting; or (c) a combination of 3% beta-alanine added for 8 d and 3 d of fasting Each maneuver lowered the cortex taurine concentration, but did not significantly lower plasma taurine values compared with controls Increased BBMV taurine uptake occurred after each manipulation Feeding 3% glycine did not alter the plasma, renal cortex, or urinary taurine concentrations, or BBMV uptake of taurine Feeding 3% methionine raised plasma and urinary taurine excretion but renal tissue taurine was unchanged, as was initial BBMV uptake Hence, nonsulfur-containing alpha-amino acids did not change beta-amino acid transport The increase in BBMV uptake correlates with the decline in renal cortex and plasma taurine content However, since 3% methionine changed plasma taurine without altering BBMV uptake, it is more likely that the change in BBMV uptake and the adaptive response expressed at the brush border surface relate to changes in renal cortex taurine concentrations Finally, despite changes in urine and renal cortex taurine content, brain taurine values were unchanged, which suggests that this renal adaptive response maintains stable taurine concentrations where taurine serves as a neuromodulator

Abstract: It is demonstrated that bile acids bind to insoluble calcium phosphate at pH values beyond 5.5. Significant binding occurs with glycine-conjugated dihydroxy bile acids. Results indicate that these bile acids are bound in a micellar mode. Taurine conjugation almost completely inhibits the binding of these bile acids to insoluble calcium phosphate. Since glycine-conjugated dihydroxy bile acids are predominant in the rabbit, but not in the rat, our results suggest an explanation for the intriguing species-dependence of casein-induced hypercholesterolaemia, which is high in the rabbit but absent in the rat.

Abstract: Dietary deprivation of taurine in pregnant cats from approximately 1 week prior to giving birth is sufficient to reduce substantially the taurine concentration in feline milk but does not result in any abnormalities in kittens at birth. Kittens nursing on this low taurine milk have a lower growth rate than normal, have lower tissue taurine concentrations, and 8 weeks after birth have a persistence of cells in the cerebellar external granule cell layer. Mitotic figures are present also, indicating that cell division is occurring still, an event which normally is completed 3–4 weeks after birth. Daily oral supplementation with 40 μmoles taurine increases the growth rate almost to the level of normally nurtured kittens and results in normal tissue taurine concentrations and apparently normal migration of cells in the cerebellum. These findings indicate that nutritional taurine supplied in the milk is involved in the normal ontogeny of the cerebellum and that a taurine deficiency at this stage of development results in a maturational delay.

Abstract: The effect of N-methyl-d,l-aspartic acid (NMA) on extracellular amino acids was studied in the rabbit hippocampus with the brain dialysis technique. Administration of 0.5 or 5 mM NMA caused a concentration-dependent liberation of taurine and phosphoethanolamine (PEA). Taurine increased by 1,200% and PEA by 2,400% during perfusion with 5 mM NMA whereas most other amino acids rose by 20–100%. The effect of NMA appeared to be receptor-mediated, as coperfusion with D-2-amino-5-phosphonovaleric acid curtailed the NMA response by some 90%. The NMA-stimulated release of taurine and PEA was suppressed when Ca2+ was omitted and further inhibited when Co2+ was included in the perfusion medium. The effect of NMA was mimicked by the endogenous NMA agonist quinolinic acid and the partial NMA agonist d,l-cis-2,3-piperidine dicarboxylic acid. Although the NMA-evoked release of taurine and PEA was Ca2+-dependent in vivo, NMA had no effect on Ca2+ accumulation in hippocampal synaptosomes. The previously reported NMA-induced activation of dendritic Ca2+ spikes and the lack of effect on synaptosomal Ca2+ uptake suggest that taurine and PEA are released from sites other than nerve terminals, possibly from dendrosomatic sites. This notion was strengthened by the absence of an effect of NMA on the efflux of radiolabelled taurine from hippocampal synaptosomes. In contrast, high K+ stimulated synaptosomal uptake of Ca2+ and release of taurine.

Abstract: The effects on retinal ganglion cells of iontophoretically applied glycine, taurine and strychnine were studied in the optically intact eye of the cat. Glycine and taurine suppressed the light-evoked discharge of all on-centre and off-centre brisk ganglion cells, regardless of the visual stimulus used. Strychnine blocked the action of externally applied glycine and taurine. The light-evoked response of all ganglion cells was raised by strychnine. The tonic discharge of the light response was suppressed or raised by the drugs more than the phasic response. A population of amacrine cells, which was heavily labelled by [3H]glycine, did not take up [3H]taurine. [3H]taurine was only weakly accumulated by inner nuclear layer neurones and was predominantly located in the outer retina.

Abstract: 1. 1. Cysteinesulfinate decarboxylase activity and taurine concentration were determined in liver and brain of rats, mice, cats, guinea-pigs and sheep. 2. 2. Values were compared for male and female animals and in some cases measurements were also made in animals of different ages. 3. 3. Cysteinesulfinate decarboxylase activity and taurine concentration were also measured in liver and brain of male and female rat pups during the postnatal period. 4. 4. Hepatic cysteinesulfinate decarboxylase activity increased in both male and female rat pups during the postnatal period and then declined markedly in female rats so that activity in adult males was 16-fold that in adult females. 5. 5. Cysteinesulfinate decarboxylase activity in liver of 5- to 6-week old kittens was 73 times that observed in liver of 15-month old cats. 6. 6. Taurine level in liver of guinea-pigs was much lower than that in liver of any other species studied.

Abstract: Patients with cystic fibrosis have an increased proportion of glycine conjugated bile acids with diminished tauroconjugates which could contribute to fat malabsorption. Twenty-two CF children with documented steatorrhea were supplemented with taurine capsules (30 mg/kg/day) and placebo during separate 6-month treatment periods. Alteration of the glycine/taurine conjugation pattern was verified in two patients who showed a predominance of tauroconjugates as a result of taurine supplementation. On taurine, steatorrhea was reduced (p less than 0.05) by 17.6 +/- 9.7% in 19 patients who completed the study as was the excretion of long-chain saturated fatty acids. There was no change in linoleic acid (C 18:2) excretion. In the 10 patients with a more severe degree of steatorrhea the decrease in fat loss approached 20% and a close relationship was found (r = 0.84, p less than 0.01) between the extent of the fatty acid loss on placebo and the decrease of this loss on taurine. A linear relationship was found between the percentage decrease of individual fatty acids and their log solubility in water. No change was found in the daily excretion of bile acids, neutral sterols, and nitrogen. Fasting plasma fatty acids, cholesterol, and triglycerides were also unchanged. Monitoring of growth over the two 6-month periods revealed a marginal (p less than 0.1) increase of weight velocity expressed as a percentage expected for age (83.4 +/- 11.3----117.1 +/- 16.5). The increase in height velocity in response to taurine showed a more modest trend (95.3 +/- 7.8----110.7 +/- 10.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: The effects in vivo of physiologic increases in insulin and amino acids on myocardial amino acid balance were evaluated in conscious dogs. Arterial and coronary sinus concentrations of amino acids and coronary blood flow were measured during a 30-min basal and a 100-min experimental period employing three protocols: euglycemic insulin clamp (plasma insulin equaled 70 +/- 11 microU/ml, n = 6); euglycemic insulin clamp during amino acid infusion (plasma insulin equaled 89 +/- 12 microU/ml, n = 6); and suppression of insulin with somatostatin during amino acid infusion (plasma insulin equaled 15 +/- 4 microU/ml, n = 6). Basally, only leucine and isoleucine were removed significantly by myocardium (net branched chain amino acid [BCAA] uptake equaled 0.5 +/- 0.2 mumol/min), while glycine, alanine, and glutamine were released. Glutamine demonstrated the highest net myocardial production (1.6 +/- 0.2 mumol/min). No net exchange was seen for valine, phenylalanine, tyrosine, cysteine, methionine, glutamate, asparagine, serine, threonine, taurine, and aspartate. In group I, hyperinsulinemia caused a decline of all plasma amino acids except alanine; alanine balance switched from release to an uptake of 0.6 +/- 0.4 mumol/min (P less than 0.05), while the myocardial balance of other amino acids was unchanged. In group II, amino acid concentrations rose, and were accompanied by a marked rise in myocardial BCAA uptake (0.4 +/- 0.1-2.6 +/- 0.3 mumol/min, P less than 0.001). Uptake of alanine was again stimulated (0.9 +/- 0.3 mumol/min, P less than 0.01), while glutamine production was unchanged (1.3 +/- 0.4 vs. 1.6 +/- 0.3 mumol/min). In group III, there was a 4-5-fold increase in the plasma concentration of the infused amino acids, accompanied by marked stimulation in uptake of only BCAA (6.8 +/- 0.7 mumol/min). Myocardial glutamine production was unchanged (1.9 +/- 0.4-1.3 +/- 0.7 mumol/min). Within the three experimental groups there were highly significant linear correlations between myocardial uptake and arterial concentration of leucine, isoleucine, valine, and total BCAA (r = 0.98, 0.98, 0.92, and 0.97, respectively); P less than 0.001 for each). In vivo, BCAA are the principal amino acids taken up by the myocardium basally and during amino acid infusion. Plasma BCAA concentration and not insulin determines the rate of myocardial BCAA uptake. Insulin stimulates myocardial alanine uptake. Neither insulin nor amino acid infusion alters myocardial glutamine release.

Abstract: A sarcolemma-enriched membrane fraction (SL) was prepared from the hearts of Sprague-Dawley rats and its ability to bind Ca++ was measured by equilibrium dialysis. We found that the effect of taurine on SL Ca++ binding varied with the buffer and with Na+ concentration. In Tris, in the presence of Na+ (140 mM), taurine (10 mM) increased the affinity but decreased the maximal binding of Ca++ (0.5-7 mM). In the absence of Na+, taurine decreased the affinity without altering the maximal binding. These effects on Ca++ binding were absent in bicarbonate or Krebs-Henseleit buffers. However, incubations with A23187, a Ca++ ionophore, and lanthanum, a Ca++ antagonist, indicated that SL membranes incubated in Tris, but not in buffers containing bicarbonate, were sealed vesicles with internal environments low in Ca++. High-affinity binding of Ca++ (10(-6)-10(-4) M) was measured in modified Krebs-Henseleit buffers. Taurine decreased Ca++ binding in a high-Na+ (145 mM), low-K+ (4.7 mM) buffer. Taurine increased Ca++ binding in both 4.7 mM Na+-145 mM K+ and 25 mM Na+-4.7 mM K+ buffers. Taurine also increased Ca++ binding in the presence of ATP. Thus, taurine increased high-affinity Ca++ binding in "intracellular" buffers, but it did not affect low-affinity Ca++ binding in "extracellular" buffers. These results suggest taurine may exert its cardiotonic actions through modulation of the high-affinity Ca++ binding sites on the internal aspect of the SL.