Unusual abundance of arginine and ornithine in porcine allantoic fluid

The concentrations of free arginine, ornithine, and glutamine in porcine allantoic and amniotic fluids were determined on Days 30,35, 40, and 45 of gestation. Arginine and ornithine were the most abundant amino acids in allantoic fluid on Days 35-40 and 45 of gestation, respectively. Arginine and ornithine nitrogen accounted for 40%, 50%, and 55% of the total free alpha-amino acid nitrogen in allantoic fluid on Days 35, 40, and 45 of gestation, respectively. Glutamine was the most abundant amino acid in amniotic fluid during early gestation and was also abundant in allantoic fluid. On Day 45 of gestation, glutamine nitrogen accounted for 41% of the total free alpha-amino acid nitrogen in amniotic fluid. The unusual abundance of arginine (2.5-4.1 mM) and ornithine (1.08-2.52 mM) in allantoic fluid on Days 35-40 of gestation has not been reported for any other biological fluid. These results are novel and interesting with respect to the role of these two basic amino acids in fetal-placental nutrition and metabolism.     

Maternal dietary protein deficiency decreases nitric oxide synthase and ornithine decarboxylase activities in placenta and endometrium of pigs during early gestation

Little is known about the mechanism responsible for retarded placental and fetal growth induced by maternal dietary protein malnutrition. On the basis of the recent finding that nitric oxide (NO) and polyamines (products of L-arginine) play an important role in embryonic and placental development, the present study was designed to determine whether protein deficiency decreases placental and endometrial activities of NO synthase (NOS) and ornithine decarboxylase (ODC) (the first and key regulatory enzyme in polyamine synthesis). Primiparous gilts selected genetically for low or high plasma total cholesterol concentrations (low line and high line, respectively) were mated and then fed 1.8 kg/d of isocaloric diets containing 13% or 0.5% crude protein. At d 40 or 60 of gestation, they were hysterectomized, and placenta and endometrium were obtained for incubations, NOS and ODC assays, and measurements of free amino acids and polyamines. Maternal dietary protein restriction decreased arginine and ornithine concentrations, constitutive and inducible NOS activities and NO production, as well as ODC activity and polyamine concentrations in placenta and endometrium of both lines of gilts. Placental NO synthase activity and NO generation were lower in high line gilts than in low line gilts. ODC activities and polyamine concentrations in placenta and endometrium were decreased at d 60 compared with d 40 of gestation. These changes in placental and endometrial synthesis of NO and polyamines during early gestation may be a mechanism responsible for reduced placental and fetal growth in protein-deficient gilts and for altered conceptus development in high line gilts.     

Age-specific distribution of plasma amino acid concentrations in a healthy pediatric population

Reference values were determined for 23 plasma free amino acids from measurements done in 148 healthy children ranging from 0 to 18 years of age. Amino acid analysis was performed by ion-exchange chromatography. We propose a graphic form of presenting the age-specific distribution of plasma amino acid concentrations where the 10th, 50th, and 90th quantiles are illustrated. Although each amino acid possesses its own pattern of distribution, we can identify five different profiles. Nine amino acids (alanine, arginine, asparagine, methionine, ornithine, phenylalanine, proline, threonine, and tyrosine) demonstrate a decrease in their concentrations during the first year of life; their concentrations then tend to increase throughout childhood and adolescence. Nine others (cystine, glutamine, glycine, histidine, isoleucine, leucine, lysine, tryptophan, and valine) show a steady increase throughout infancy, childhood, and adolescence. Five amino acids (aspartic acid, citrulline, glutamic acid, serine, and taurine) do not follow these two common profiles. For the first time, quantile curves are produced to illustrate the age-dependent variation of amino acid concentrations from infancy to adulthood. This alternative way of presenting amino acid concentrations may facilitate the follow-up of patients with inborn errors of amino acid metabolism.     

Effects of L-DOPA/carbidopa administration on the levels of L-DOPA, other amino acids and related compounds in the plasma, brain and heart of the rat

Rats were treated intraperitoneally with a mixture of 250 mg/kg L-DOPA and 40 mg/kg carbidopa or with vehicle and sacrificed 30 min later. Plasma, heart and cortex, midbrain, brainstem and cerebellum were removed from each animal and assayed by HPLC for L-DOPA and a large number of amino acids and related amino compounds. L-DOPA levels increased from undetectable (<0.2 nmol/ml or g) to 1,146, 1,007, 399, 376, 368 and 850 nmol/ml or g in the above tissues. In addition, several amino compounds were significantly affected by L-DOPA/carbidopa (p < or = 0.01). Plasma concentrations of phosphoserine, oxidized glutathione, citrulline, phenylalanine, tyrosine and 1-methylhistidine increased and arginine, glutamic acid and lysine decreased. In the heart, concentrations of phosphoserine, taurine, reduced glutathione, threonine, serine, glutamine, glycine, alanine, valine, GABA, ethanolamine, ammonia and arginine decreased. In the cortex, camosine and homocarnosine increased. In the midbrain, valine increased and leucine, ornithine and oxidized glutathione decreased. In the cerebellum, citrulline increased. In the brainstem, threonine, serine, asparagine, glutamine, oxidized glutathione, alanine, and leucine decreased. In the brainstem, arginine was slightly decreased with a concomitant increase in citrulline (p < 0.05), indicative of nitrous oxide formation. These results show that administration of L-DOPA/ carbidopa not only raises dopamine levels but can also affect other biochemicals and that the observed changes in amino acids and related compounds can perhaps contribute to the beneficial and/or adverse effects of L-DOPA/carbidopa therapy of Parkinson's disease.     

Urinary excretion of amino acids in normal and cystinuric dogs

The 24-h urine excretion of 20 amino acids was investigated in 24 cystinuric and 15 normal dogs. The diagnosis of cystinuria was based on infrared spectroscopy of removed uroliths, which in all cases were composed of pure cystine. Seven of 24 cystinuric dogs showed normal cystine excretion compared to normal dogs, and four of 24 dogs showed normal total amino acid excretion. In contrast to earlier investigations, almost half of the cystinuric dogs (46%) showed elevated excretion of five or more amino acids. Isolated cystinuria, or isolated dibasic amino aciduria was not found. Compared to normal dogs, the cystinuric dogs showed a significantly (P < 0.05) increased excretion of cystine, arginine, lysine, cystathionine, glutamic acid, threonine and glutamine. There was a significant correlation (P < 0.05) between the urinary excretion of cystine and 10 other amino acids, with the highest correlation found (P < 0.001) for arginine, lysine, cystathionine, ornithine and 1-methyl-histidine. Three patterns of amino acid excretion could be identified: (1) increased excretion and a significant correlation with cystine for the three dibasic amino acids (lysine, arginine and ornithine), compatible with a common reabsorption mechanism as shown in man. This pattern was also found for cystathionine and glutamic acid, which might indicate a relation in metabolism or transport; (2) increased excretion but no correlation with cystine for glutamine, threonine and citrulline; (3) good correlation with cystine, but no increased excretion for 1-methyl-histidine, phenylalanine, 3-methyl-histidine, leucine and alanine. The great variation in urinary cystine excretion suggests that factors other than the excretion of cystine must be considered as causes of cystine urolith formation. For example, cystinuric dogs were found to have lower diuresis than normal dogs and produced urine with higher cystine concentration thereby increasing the risk of cystine urolith formation.     

Plasma amino acids in anorexia nervosa

OBJECTIVE: To evaluate the amino acid profile in a group of adolescents with anorexia nervosa, and to apply alternative ways of presenting and assessing results, so as to increase the information available for understanding the metabolic abnormalities developed in these patients. DESIGN: Plasma amino acid concentrations of a random group of patients with anorexia nervosa compared with values obtained from a 'healthy' adolescent population. SETTING: The study was performed at the tertiary children's Hospital Sant Joan de Deu. SUBJECTS: Female adolescents (n = 92, age: 15+/-1.8 y) at diagnosis of anorexia nervosa. Reference values for amino acids were obtained from apparently healthy adolescents (by history and analytical data) who underwent presurgical analysis for minor operations. Interventions: Plasma amino acid concentrations were measured by ion exchange chromatography. Basic laboratory analysis, carnitine and IGF-I were also determined. RESULTS: In anorexic patients plasma concentrations of taurine, asparagine, glutamine, glycine, methionine, phenylalanine, ornithine, and histidine were significantly higher than reference values (Mann-Whitney, P < 0.01-0.0001), whereas arginine and cystine were lower than our reference values (P < 0.0001). Relative amino acid values (the molar fraction of the patient medians relative to control medians) were plotted. The ratios of some amino acids were significantly greater than those obtained from the reference population: Phe/Tyr (P < 0.001), Met/Cys (P < 0.0001), and Gly/Val (P < 0.01). CONCLUSIONS: A trend to hyperaminoacidemia is a common feature in anorexia nervosa. Although absolute amino acid values cannot play a significant role in the assessment of nutritional status in this condition, the calculation of some ratios (Phe/Tyr, Met/Cys and Gly/Val) and the graphical representation of relative values may be useful. The plasma amino acid profile in anorexia nervosa is different from those of other severe malnutrition states, showing a marasmic pattern of balanced protein-energy undernutrition. Cystine and arginine may be considered limiting amino acids in this disease, and the consequences of their deficient concentrations for oxidative damage should be further evaluated.     

Endogenous synthesis of arginine plays an important role in maintaining arginine homeostasis in postweaning growing pigs

This study was conducted to determine whether endogenous synthesis of arginine plays a role in regulating arginine homeostasis in postweaning pigs. Pigs were fed a sorghum-based diet containing 0. 98% arginine and were used for studies at 75 d of age (28.4 kg body weight). Mitochondria were prepared from the jejunum and other major tissues for measuring the activities of Delta1-pyrroline-5-carboxylate (P5C) synthase and proline oxidase (enzymes catalyzing P5C synthesis from glutamate and proline, respectively) and of ornithine aminotransferase (OAT) (the enzyme catalyzing the interconversion of P5C into ornithine). For metabolic studies, jejunal enterocytes were incubated at 37 degrees C for 30 min in Krebs-Henseleit bicarbonate buffer containing 2 mmol/L L-glutamine, 2 mmol/L L-[U-14C]proline, and 0-200 micromol/L gabaculine (an inhibitor of OAT). The activities of P5C synthase, proline oxidase and OAT were greatest in enterocytes among all of the tissues studied. Incubation of enterocytes with gabaculine resulted in decreases (P < 0.05) in the synthesis of ornithine and citrulline from glutamine and proline. When gabaculine was orally administered to pigs (0.83 mg/kg body weight) to inhibit intestinal synthesis of citrulline from glutamine and proline, plasma concentrations of citrulline (-26%) and arginine (-22%) decreased (P < 0.05), whereas those of alanine (+21%), ornithine (+17%), proline (+107%), taurine (+56%) and branched-chain amino acids (+21-40%) increased (P < 0.05). On the basis of dietary arginine intake and estimated arginine utilization, the endogenous synthesis of arginine in the 28-kg pig provided >/=50.2% of total daily arginine requirement. Taken together, our results suggest an important role for endogenous synthesis of arginine in regulating arginine homeostasis in postweaning growing pigs, as previously shown in neonatal pigs.     

Monitoring of isotretinoin therapy by measuring the plasma levels of isotretinoin and 4-oxo-isotretinoin. A useful tool for management of severe acne

Folate-binding proteins (FBP) from Day 60 pseudopregnant uterine flushings and Day 60 allantoic fluid were purified by affinity chromatography on folate-Sepharose followed by G-100 Sephadex chromatography. FBP from uterine flushings had a molecular weight of 20000; the N-terminal sequence was FNWDHXGKMEPAXKRHFXXXTXLYX, which is 72% identical to bovine milk FBP beginning at amino acid 64. Allantoic fluid FBP had a molecular weight of 30000; and the N-terminal sequence ARAKTDMLNVXMDAKHHKPKPSXED, which is 68% identical to bovine milk FBP starting at amino acid 4. Scatchard analysis of purified allantoic fluid FBP using [3H]folic acid as ligand indicated a dissociation constant of 0.54 nM, and the protein was saturated at 20 nM. Antiserum to the purified allantoic fluid FBP was generated in rabbits and used for immunoblotting. Uterine flushings were collected from pregnant and nonpregnant gilts on Days 10, 11, 12, 13, and 15. Immunoblotting indicated that FBP concentrations increased in uterine flushings from both pregnant and nonpregnant gilts between Days 10 and 15. Total uterine flush specific binding of [3H]folic acid increased from 0.015 nmol on Day 10 to 2.14 nmol on Day 15. These results indicate that an FBP similar to other known FBPs is present in uterine flushings and allantoic fluid and that its level increases at about the time of blastocyst elongation and initiation of conceptus hematopoiesis. These results suggest a role for FBP in the delivery of folate to the developing conceptus.     

The callosal connections of the hierarchically organized somatosensory areas of primates

The Royal College of Surgeons' (RCS) rat is an experimental model for a group of hereditary retinal diseases commonly called retinitis pigmentosa. We used postembedding immunocytochemistry to determine the localisation of glutamate, gamma-aminobutyric acid (GABA), glycine, aspartate, glutamine, taurine, and arginine in the RCS rat retina during postnatal development. In addition, we evaluated the uptake characteristics for the three dominant amino acid neurotransmitters, glutamate, GABA, and glycine. Whereas, cellular localisation of all amino acids was similar to control retinas, there were major changes in the level of immunoreactivity, even before eye opening, and well before the onset of visibly detectable photoreceptor degeneration. Two major patterns emerged. First, neurochemical changes evident before degeneration, involving the amino acids glutamate, GABA, aspartate, glutamine, and arginine. Second, neurochemical changes that become evident during photoreceptor degeneration involving the amino acids taurine and glycine. Anomalies in uptake characteristics also become evident during the degeneration phase and are likely to reflect changes in cellular function as a consequence of the degeneration process. Neurochemical changes evident before photoreceptor degeneration involve both glutamate and GABA manufacturing pathways. Müller's cells displayed elevated levels of glutamine and arginine from an early age, and the neuroblastic layer in the RCS retina showed high glutamate levels. Modified aspartate immunoreactivity began at postnatal day 11 and is consistent with altered metabolic activity. These results suggest that amino acid neurochemistry is different in the RCS rat retina from an early age, which may indicate an underlying metabolic defect affecting multiple cell classes.     

Effects of repeated cerebral ischemia on extracellular amino acid concentrations measured with intracerebral microdialysis in the gerbil hippocampus

BACKGROUND AND PURPOSE: To clarify the role of elevated extracellular amino acid concentrations during ischemia on the cumulative neuronal damage after repeated cerebral ischemic insults, using a microdialysis technique we measured concentrations of the amino acids glutamate, glutamine, glycine, taurine, and gamma-aminobutyric acid in the gerbil hippocampus over three 2-minute forebrain ischemic insults induced at 1-hour intervals. METHODS: Under light anesthesia, the bilateral common carotid arteries were occluded with aneurysm clips at 1-hour intervals. Samples were collected by microdialysis at 10-minute intervals, and the amino acid concentrations were determined using a high-performance liquid chromatography system. RESULTS: During and immediately after the first ischemic insult, concentrations of glutamate, glycine, and taurine, but not glutamine, increased significantly. Glutamate and taurine concentrations rose again during the second and third ischemic insults, but the increases were smaller than those during the first insult. By contrast, glutamine concentrations increased slightly but significantly during the second and third ischemic insults. The extracellular concentration of gamma-aminobutyric acid before the ischemic insults was below the level of detectability but increased markedly during each ischemic insult, with similar declines in the amounts released during later insults. Concentrations of all amino acids returned to baseline after 10 minutes of reperfusion and remained at baseline until the subsequent ischemic insult was induced. CONCLUSIONS: It is well established that glutamate released during ischemia plays a crucial role in ischemia-induced neuronal death. However, the present results indicate that cumulative neuronal damage following sublethal ischemic insults is not caused by an exaggerated release of excitatory amino acids during subsequent ischemic insults but strongly suggest that increased intracellular reactions leading to cell death play a major role.     

Hyperdibasicaminoaciduria and hyperammonemia in familial protein intolerance

A 3-year-old boy with hyperdibasicaminoaciduria and hyperammonemia showed characteristics of familial protein intolerance (FPI). Oral loading tests of lysine and arginine disclosed a remarkably reduced capability for intestinal absorption of these amino acids. Because urinary excretion and renal clearance of dibasic amino acids were only moderately elevated in the patient, the conspicuously decreased serum concentration of lysine, arginine, and ornithine was attributed to the defect in internal absorption. A possible explanation for elevated blood ammonia levels in FPI is that it is due to a deficiency of arginine and ornithine in the urea cycle that in turn results from a severe impairment in absorption of the amino acids by the gut mucosa.     

The utilization of amino acids and urea by human oral fluid

Incubation of mixed human saliva with arginine, ornithine, and proline for 30 min to 2 h at 40 degrees C leads to an appreciable consumption of the above amino acids. The rate of utilization is 0.2 to 0.5 ncat/ml of saliva. The rate of urea loss is higher by an order of magnitude: up to 11 ncat/ml. Putrescin, urea (after incubation with arginine), and ammonium are identified as the products of these reactions. The biological significance of such reactions is believed to consist in neutralization of carbohydrate fermentation products. The detected consumption of amino acids and urea indicates that mixed human saliva contains urease, arginase, ornithine decarboxylase, and, probably, proline reductase. Since the origin of these enzymes is probably bacterial, changes in their activity in the saliva can be regarded as an indicator of dysbacteriosis and a diagnostically important parameter.     

Endocrine-metabolic response to acute starvation in human gestation

During a 72 hour fast in pregnant women, significant decrements in the maternal plasma glucose concentrations, accompanied by a significant increase in the plasma placental lactogen (hPL) concentration, occur. At the same time, utilization of glucogenic amino acids, principally alanine, takes place. The mean postprandial glucose concentration in pregnancy is significantly lower than that of comparable nonpregnant women (70.5 +/- 1.7 versus 79.5 +/- 1.3 mg. per 100 ml., p less than 0.001). There appears to be a significant sparing effect on the maternal plasma glucose concentration during acute fasting which may be mediated through hPL. Concentrations of amniotic fluid and fetal plasma glucose from women undergoing fasting decrease in a manner parallel to that of the mother. Fasting provokes a mean rise in plasma hPL of 33.2 per cent over basal levels. This rise is still evident 72 hours after refeeding, after which it gradually returns to pretest concentrations. The infusion of alanine or arginine to pregnant women at the end of the fast produced increments in the peripheral maternal glucose concentration. The response was much greater with alanine than with arginine, demonstrating the increased gluconeogenic potential of this amino acid. The increment in human growth hormone (hGH) following alanine infusion was significantly greater than that observed after arginine administration. Hypoaminoacidemia was present in nonpregnant and pregnant women in response to fasting, but the decline was greater in pregnancy. Acute fasting in the first half of gestation appears to produce significant alterations in carbohydrate metabolism evidenced by profound hypoglycemia, hypoinsulinemia, and hypoaminoacidemia. This maternal deficit can be reflected in fetal substrate concentrations. The effect of these changes on fetal growth and development is speculative at this time.     

Optimum amino acid complement for protein synthesis by rat mammary cells in tissue culture

The amino acid requirement of rat mammary cells for milk protein synthesis was investigated in dispersed cell culture. A three-dimensional central composite design utilizing three variables (X1 = lysine; X2= methionine, valine, and arginine; X3 = isoleucine, tryptophan, threonine, phenylalanine, and histidine) at five concentrations each, was duplicated twice with mammary cells from lactating Sprague-Dawley rats. The optimum combination of amino acids for maximum milk protein synthesis from multiple regression models was X1 15.0-, X2 4.5-, and X3 1.5-fold their quantities in Eagle's minimal essential medium with leucine, tyrosine, cystine, and glutamine at the base 1-fold in the medium.     

Protein kinase inhibitors attenuate cardiac swelling-induced amino acid release in the rat

Rat Langendorff heart preparations have been used to study the efflux of cardiac amino acids into coronary artery perfusates during brief (5-min) periods of exposure to hyposmotic stress (70 mM NaCl). Coronary flow rates, heart rates and intra-aortic pressures were recorded. Amino acid levels were measured by high-performance liquid chromatography. Hyposmotic stress caused marked percentage increases in taurine, glutamate and aspartate levels in the coronary perfusate, with smaller increases in phosphoethanolamine, glycine and alanine and non-significant increases in serine and glutamine. Amino acid levels declined during reperfusion with isosmotic Krebs-Henseleit bicarbonate buffer. Inhibition of protein kinase C with chelerythrine chloride (5 microM) depressed the osmotically-induced release of aspartate, glutamate, taurine and glycine. The protein tyrosine kinase inhibitor, genistein, reduced the anisosmotic efflux of aspartate, glutamate, taurine and phosphoethanolamine. Lavendustin A, another inhibitor of tyrosine kinase, depressed the osmotically evoked release of aspartate, glutamate and taurine. These studies demonstrate the involvement of protein kinase C and tyrosine kinases in the efflux of amino acids from the osmotically challenged rat heart and imply that these enzymes are involved in the mechanisms responsible for volume regulation by cardiac cells.     

Effect of ischaemia and reperfusion on the intracellular concentration of taurine and glutamine in the hearts of patients undergoing coronary artery surgery

Taurine and glutamine are the most abundant intracellular free amino acids in mammalian hearts where changes in their intracellular concentrations are likely to influence a number of cellular activities. In this study we investigated the effects of ischaemia and reperfusion on the intracellular concentrations of taurine and glutamine in the hearts of patients undergoing coronary artery bypass surgery using cold crystalloid or cold blood cardioplegic solutions. Ischaemic arrest (30 min), using cold crystalloid cardioplegic solution (n = 19), decreased the intracellular concentrations (micromol/g wet weight) of taurine (from 9.8 +/- 0.8 to 7.7 +/- 0.7, P < 0.05) and glutamine (8.7 +/- 0.5 to 7.2 +/- 0.6). After 20 min of normothermic reperfusion the fall in taurine and glutamine was maintained (7.5 +/- 0.5 and 7.4 +/- 0.7 for taurine and glutamine respectively). Myocardial ischaemic arrest with cold blood cardioplegic solution (n = 16) did not cause a significant fall in tissue taurine or glutamine. However, on reperfusion there was a marked fall in the intracellular concentrations of taurine (9.4 +/- 0.5 to 6.5 +/- 0.7) and glutamine (8.0 +/- 0.7 to 5.8 +/- 0.4). The fall in amino acids was associated with a fall in ATP and a rise in tissue lactate. This work demonstrates that irrespective of the cardioplegic solution used to arrest the heart, there is a marked fall in tissue taurine and glutamine which may influence the extent of recovery following surgery. The fall in taurine is largely due to efflux whereas changes in glutamine are due to both transport and metabolism. Ischaemia, hypothermia and changes in the transmembrane concentration gradients are the likely factors responsible for the changes in tissue amino acids.     

Comparison of leucine, serine and glycine transport across the ovine placenta

To estimate the transport rate of maternal glycine across the placenta [1-13C]glycine and L-[1-13]serine were infused intravenously in pregnant sheep using both continuous and bolus infusions. Each tracer was infused together with L-[1-13C]leucine, to enable a comparison with the placental transport of an essential amino acid. At steady state, fetal plasma leucine enrichment was 40 per cent of maternal enrichment, indicating that approximately 60 per cent of the entry rate of leucine into fetal plasma is derived from protein breakdown in the placenta and fetus. Fetal plasma glycine enrichment was 11 per cent of maternal and there was no detectable fetal serine enrichment. The direct flux of maternal leucine into the fetal circulation was approximately 3.0 (bolus experiments) to 3.6 (continuous infusion experiments) mumol/min (kg fetus) and greater than the estimated 1.4 mumol/min (kg fetus) direct flux of maternal glycine, despite the fact that the net umbilical uptake of glycine exceeds that of leucine. This supports the conclusion that placental glycine production is a quantitatively important contribution to fetal glycine uptake via the umbilical circulation. The fetal glycine supply from the placenta is provided by a relatively small direct maternal glycine transplacental flux and a larger contribution derived from serine utilization within the placenta for glycine production.     

Female choice and manipulations of forceps size and symmetry in the earwig Forficula auricularia L

Nutrition influences the reproductive axis via alteration of gonadotrophin secretion. However, a link between nutrition and the secretion of GnRH, which drives the axis, has yet to be established. The aim of the present study was to measure the change in the concentrations of metabolic substances in the cerebrospinal fluid of adult male sheep offered a diet designed to maintain constant gonadotrophin secretion (Group M; n = 6), or a diet known to increase gonadotrophin secretion (Group M + L; n = 6). On days 1, 3 and 10 of the dietary treatments, cerebrospinal fluid and jugular blood were sampled and analysed for metabolic fuels (glucose, amino acids and free fatty acids) and metabolic hormones (insulin, insulin-like growth factor I, GH, prolactin, cortisol and the thyroid hormones). On day 11 of the dietary treatment, LH pulse frequency and mean FSH concentrations in Group M + L had increased relative to Group M and to day 0. Plasma concentrations of prolactin and insulin on days 3 and 10, and glucose and insulin-like growth factor I on day 10, were higher in Group M + L than in Group M, but only cerebrospinal fluid concentrations of insulin, glucose and certain amino acids were affected by the dietary treatments on days 3 and 10. Cerebrospinal fluid, but not plasma, concentrations of aspartate, tyrosine, cystine, phenylalanine and arginine on day 3, and glutamine, gamma-aminobutyric acid, threonine, alanine on days 3 and 10, were higher in Group M + L relative to Group M. On day 10, plasma and cerebrospinal fluid concentrations of arginine, phenylalaine, proline, tyrosine, methionine and phosphoserine, but only the plasma concentrations of linoleic acid, aspartate and serine, were higher in Group M + L than in Group M. Concentrations of triiodothyronine, thyroxine, and cortisol in plasma and cerebrospinal fluid were not affected. These results show that the nutritional stimulation of gonadotrophin secretion is accompanied primarily by fluctuations in plasma and cerebrospinal fluid concentrations of insulin and certain amino acids, which suggests that, when nutritional status is improved, insulin, amino acids and possibly glucose interact to modulate GnRH secretion.     

Ontogeny of neurotransmitter amino acids in human fetal brains

A wide spectrum of developmental profiles is presented for a few important neurotransmitter amino acids, namely gamma-aminobutyric acid, glycine, glutamic acid, aspartic acid and taurine as well as the key enzymes involved in their metabolism in human fetal brains of different gestational ages. Besides taurine almost all these amino acids and their key metabolic enzymes were found to be progressively enhanced upto the mid period of third trimester of pregnancy indicating a rapid growth of nerve processes, myelination and maturation of fetal brains particularly during this period. Interestingly taurine showed an inverse relationship of ontogenic pattern with respect to its biosynthesizing enzyme in fetal brains.     

Selective alterations of extracellular brain amino acids in relation to function in experimental portal-systemic encephalopathy: results of an in vivo microdialysis study

Portal-systemic encephalopathy (PSE) is characterized by neuropsychiatric symptoms progressing through stupor and coma. Previous studies in human autopsy tissue and in experimental animal models of PSE suggest that alterations in levels of brain amino acids may play a role in the pathogenesis of PSE. To assess this possibility, levels of amino acids were measured using in vivo cerebral microdialysis in frontal cortex of portacaval-shunted rats administered ammonium acetate (3.85 mmol/kg, i.p.) to precipitate severe PSE. Sham-operated rats served as controls. Portacaval shunting resulted in significant increases of levels of extracellular glutamine (threefold, p < 0.001), alanine (38%, p < 0.01), aspartate (44%, p < 0.05), phenylalanine (170%, p < 0.001), tyrosine (140%, p < 0.001), tryptophan (63%, p < 0.001), leucine (75%, p < 0.001), and serine (60%, p < 0.001). Administration of ammonium acetate to sham-operated animals led to a significant increase in extracellular glutamine and taurine content, but this response was absent in shunted rats. The lack of taurine release into extracellular fluid following ammonium acetate administration in portacaval-shunted rats could relate to the phenomenon of brain edema in these animals. Ammonium acetate administration resulted in significant increases in the extracellular concentrations of phenylalanine and tyrosine in both sham-operated and portacaval-shunted rats. Severe PSE was not accompanied by significant increases in extracellular fluid concentrations of glutamate, aspartate, GABA, tryptophan, leucine, or serine, suggesting that increased spontaneous release of these amino acids in cerebral cortex is not implicated in the pathogenesis of hepatic coma.