Effects Of L-phenylalanine Research Articles

Screening inhibitor to prevent the psychrotrophic growth of Pseudomonas fluorescens by using molecular simulation

Pseudomonas fluorescens is a specific spoilage bacteria in seafood, which has the ability to maintain growth and reproduction at low temperatures. There are some functional proteins in Pseudomonas fluorescens to defense the harm of cold to its life activities. Hence, disrupting this defense mechanism may be a good way to control food spoilage. In this study, we screened the food ingredients database to search for potential cold defense mechanism inhibitors of P. fluorescens PF08 by using virtual screening. From the screening results, we found a compound with inhibitory activity — l-phenylalanine. Moreover, the effects of l-phenylalanine on the cold defense mechanism were determined. l-phenylalanine is difficult to inhibit bacterial growth at room temperature. However, it significantly inhibits the growth ability of Pseudomonas fluorescens PF08 and the production of biofilm at 4 °C. In addition, we also found that l-phenylalanine can compress RpoS and Algk, which undoubtedly interferes with the function of proteins.

Effects of L-Phenylalanine on Energy Intake and Glycaemia-Impacts on Appetite Perceptions, Gastrointestinal Hormones and Gastric Emptying in Healthy Males.

In humans, phenylalanine stimulates plasma cholecystokinin (CCK) and pyloric pressures, both of which are important in the regulation of energy intake and gastric emptying. Gastric emptying is a key determinant of postprandial blood glucose. We evaluated the effects of intragastric phenylalanine on appetite perceptions and subsequent energy intake, and the glycaemic response to, and gastric emptying of, a mixed-nutrient drink. The study consisted of two parts, each including 16 healthy, lean males (age: 23 ± 1 years). In each part, participants received on three separate occasions, in randomised, double-blind fashion, 5 g (Phe-5 g) or 10g (‘Phe-10 g) L-phenylalanine, or control, intragastrically, 30 min before a standardised buffet-meal (part A), or a standardised mixed-nutrient drink (part B). In part A, plasma CCK and peptide-YY (PYY), and appetite perceptions, were measured at baseline, after phenylalanine alone, and following the buffet-meal, from which energy intake was assessed. In part B, plasma glucose, glucagon-like peptide-1 (GLP-1), insulin and glucagon were measured at baseline, after phenylalanine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured by 13C-acetate breath-test. Phe-10 g, but not Phe-5 g, stimulated plasma CCK (p = 0.01) and suppressed energy intake (p = 0.012); energy intake was correlated with stimulation of CCK (r = −0.4, p = 0.027), and tended to be associated with stimulation of PYY (r = −0.31, p = 0.082). Both Phe-10 g and Phe-5 g stimulated insulin and glucagon (all p < 0.05), but not GLP-1. Phe-10 g, but not Phe-5 g, reduced overall plasma glucose (p = 0.043) and peak plasma glucose (p = 0.017) in response to the mixed-nutrient drink. Phenylalanine had no effect on gastric emptying of the drink. In conclusion, our observations indicate that the energy intake-suppressant effect of phenylalanine is related to the stimulation of CCK and PYY, while the glucoregulatory effect may be independent of stimulation of plasma GLP-1 or slowing of gastric emptying.

The immunologic and antioxidant effects of L-phenylalanine on the uterine implantation of mice embryos during early pregnancy.

L-phenylalanine (L-PHE) is a synthetic precursor of catecholamines. Because it cannot be synthesised by an organism, it must be absorbed from the environment. Despite the wide use of L-PHE, whether L-PHE has a negative impact on embryo implantation and development is poorly understood. This study attempted to determine the roles of L-PHE in embryo implantation and development and in the immune response and antioxidant status of the uterus in early pregnancy mice injected intraperitoneally with 320 mg/kg L-PHE. The embryo number of treated mice decreased by 57.6%, and the size of their embryos was reduced by 2.8% (P⟩0.05) along the long diameter and 11.9% (P⟨0.05) along the short diameter at E9 compared with control mice. In addition, L-PHE significantly suppressed B lymphocyte proliferation. L-PHE increased IL-2 secretion but decreased the IL-4 concentration, thereby up-regulating the ratio of IL-2/IL-4 to 1.37-8.45. An analysis of the oxidant and antioxidant status showed that, compared with the control mice, the level of superoxide dismutase activity decreased by 21.54-39.94% and the glutathione peroxidase activity decreased by 15.27-18.96% among the L-PHE-treated mice at E1-E9. However, the malonaldehyde content increased by 14.29%-90.11% among the L-PHE-treated mice. Therefore, L-PHE impaired embryo implantation by disrupting cytokine-based immunity and oxidative stress in the uterus.

Effect of l-phenylalanine on PAL activity and production of naphthoquinone pigments in suspension cultures of Arnebia euchroma (Royle) Johnst

The effects of l-phenylalanine (PHE) on cell growth and production of shikonin and its derivatives, acetylshikonin (ACS) and isobutyrylshikonin (IBS), in suspension cultures of Arnebia euchroma were examined. Supplementing media using PHE have been successfully utilized to enhance shikonin production in cell cultures of other species of Boraginaceae. l-Phenylalanine, the key compound in the phenylpropanoid pathway, is converted by phenylalanine ammonia lyase (PAL) to trans-cinnamic acid, which is the precursor of p-hydroxybenzoic acid (PHB). Coupling of PHB and geranyl pyrophosphate (derived from mevalonate pathway) by p-hydroxybenzoate-m-geranyltransferase leads later to biosynthesis of shikonins. The addition of 0.01 or 0.1 mM PHE to the culture medium stimulated cell proliferation, where the highest observed increase in fresh cell biomass (measured as a ratio of final weight to initial weight) was 12-fold, in contrast to an eightfold increase in control cultures. Whereas, growth media supplemented with 1 mM PHE markedly reduced the rate of cell growth (to only twofold). Precursor feeding had detrimental effects on both ACS and IBS production in all PHE-supplemented media. The highest total content (intracellular + extracellular) of the investigated red pigments (9.5 mg per flask) was detected in the control culture without PHE. ACS was the major component of the naphthoquinone fraction determined in cells and post-culture media. Shikonin itself was found only in the post-culture media from cultures supplemented with 0.01 or 0.1 mM PHE. Increases in PAL activity corresponded well with the accumulation of investigated naphthoquinones in control culture. However, peak PAL activity did not directly correlate with maximum production of shikonin derivatives. Cytotoxicity of extracts, prepared from the cells cultivated in the presence of PHE or in control cultures, was tested on three cancer cell lines: HL-60, HeLa, and MCF-7. The extracts prepared from the untreated control cultures proved to be the most potent against the examined cancer cell lines. The mean inhibitory concentration values were 0.3, 13, and 8 μg ml−1 for the HL-60, HeLa, and MCF-7 cells, respectively.

Effects of l-phenylalanine on energy intake in overweight and obese women: Interactions with dietary restraint status

l-Phenylalanine (Phe), is a potent releaser of the satiety hormone, cholecystokinin (CCK) and previous studies, conducted primarily in men, show that ingestion of Phe reduces energy intake. The objective of the current study was to test the effects of Phe on energy intake in overweight and obese women. Subjects ( n = 32) received three treatments (high-dose (10 g Phe), low-dose (5 g Phe and 5 g glucose) or control (10 g glucose)) 20 min before an ad libitum lunch and dinner meal in a within-subjects’, counterbalanced, double-blind study. No effect of Phe was found, however, interactions with dietary restraint status were detected in post-hoc analyses. Energy intake over the day was 11% lower following high-dose Phe versus control for women classified in the lower tertile of rigid restraint, a subscale of the dietary restraint scale, whereas no effects were noted for women in the middle and upper tertiles. High-dose Phe increased ratings of nausea, however, reduced energy intake in the high-dose condition was noted only for subjects with low nausea ratings. These results suggest that the satiety response to Phe is modulated by rigid restraint status and that reductions in food intake occur independently of Phe's effects on nausea.

Effects of l-phenylalanine on acetylcholinesterase and Na +, K +-ATPase activities in adult and aged rat brain

The effect of different l-phenylalanine (Phe) concentrations (0.12–1.8 mM) on acetylcholinesterase (AChE), (Na +, K +)-ATPase and Mg 2+-ATPase activities was investigated in homogenates of adult and aged rat whole brain at 37°C. Adult and aged rat experiments were necessary in relation to phenylketonuria (PKU) since phenylketonuric patients usually discontinue their therapeutic special diet when they reach adulthood. Diet discontinuation results in the pathological increase of Phe concentration in plasma and consequently in brain. AChE activity in adult brain homogenates showed a decrease up to 18% ( P<0.01) with 0.48–1.8 mM Phe preincubated for 1 h. Adult brain Na +, K +-ATPase was stimulated by 30–35% ( P<0.01) in the presence of 0.48–1.8 mM Phe. However, high Phe concentrations were not able to affect the activities of AChE and Na +, K +-ATPase, when preincubated with aged brain homogenate for 3 h. Moreover, high Phe concentrations appeared unable to affect the activity of eel E. electricus pure AChE inhibited about 30% ( P<0.001) by the free radical system H 2O 2/Fe 2+. Also, the antagonists of α- and β-adrenergic receptors (phenoxybenzamine and propranolol, respectively) inhibited adult rat brain Na +, K +-ATPase activity about 30–40% ( P<0.01) and Phe was unable to change this action. It is suggested that: (a) The inhibitory effect of Phe on brain AChE and its stimulatory effect on brain Na +, K +-ATPase are decreased with age; (b) These effects may be influenced by aging factors, such as free radical action and/or reduced density of α- and β-adrenergic receptors in the tissue.

Effects of L-phenylalanine on somite formation in the early chick embryo

Chick embryos were treated in ovo and in vitro with L-phenylalanine from the intermediate streak stage (Hamburger & Hamilton stage 3, 12-13 h of incubation) to the 7-somite stage (H & H stage 9, 29-33 h of incubation). Treatment in ovo resulted in a large number of embryos developing somite blocks, i.e. imperfectly segmented somites. In embryos treated at an early developmental stage (12-21 h of incubation), the blocks of unsegmented somite mesoderm occurred mostly in the somite pairs 1-5, whereas treatment that began at a later stage (24-30 h of incubation) caused blocks in the somite pairs 5-10, i.e. the appearance of blocks of unsegmented somite mesoderm is correlated in time with the onset of the treatment. No difference regarding mitotic indices could be distinguished between normally segmented somites and blocks of unsegmented somite mesoderm. Autoradiography based on tritiated L-phenylalanine showed no regional differences in labelling of the chick embryo body. Electronmicroscopical observations indicate a slightly suppressed formation of microvilli in the cells of the unsegmented mesoderm blocks compared with cells in normally segmented somites. The observed disturbances are probably caused by a suppressed yolk granule decomposition in the developing somite cells. The experiments in vitro support the findings in the in ovo material; at the same time, they reveal an unexpectedly slow diffusion of L-phenylalanine through the vitelline membrane.

Effects of L-phenylalanine on alkaline phosphatase activity and ion and water absorption in the eel intestine

1. Specific inhibition of intestinal alkaline phosphatase by L-phenylalanine was shown in eels adapted to both seawater and freshwater. 2. L-phenylalanine-sensitive alkaline phosphatase was demonstrated histochemically at the luminal surface of the sea water eel intestine. 3. Net absorption of water, Na + and Cl − by the everted intestine was reduced significantly by adding L-phenylalanine to both internal and external Ringer incubation medium. 4. No appreciable change in transepithelial potential difference was observed by adding 30 mM L-phenylalanine to NaCl, sulfate or choline Ringer solutions.

Experimental phenylketonuria: Metabolic studies in rat liver

The "in vivo" effects of L-phenylalanine on the gluconeogenic pathway in the liver of fasted rats with experimentally induced phenylketonuria-like characteristics have been investigated. Significant increases of the fructose 6-phosphate, glucose 6-phosphate and glucose concentrations were observed. The study of the effect of L-phenylalanine on the cytoplasmic and mitochondrial redox state and energy charge showed an increase in the mitochondrial NAD+/NADH ratio while the energy charge was virtually unchanged. The effects of phenylalanine and its metabolic derivatives (phenylacetate, phenylethylamine, phenyl-lactate, o-hydroxyphenylacetate and phenylpyruvate) on the activity of lactate dehydrogenase (EC 1.1.1.27), malate dehydrogenase (EC 1.1.1.37) and 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) in rat liver have been also investigated. Phenylpyruvate inhibited the lactate dehydrogenase activity with a Ki of 5.3 mM. Phenylpyruvate also inhibited both the mitochondrial (Ki = 4 mM) and cytoplasmic (Ki = 5 mM) malate dehydrogenase activities. Phenylpyruvate, phenylacetate and o-hydroxyphenylacetate inhibited the 3-hydroxybutyrate dehydrogenase activity with Ki values of 0.7, 6.0 and 9.5 mM respectively.

Inhibition of intestinal absorption of phenylalanine by phenylalaninol.

Plasma phenylalanine and tyrosine levels in rats which had been orally administered L-phenylalaninol and L-phenylalanine were determined. Since these amino acid levels in rats administered L-phenylalanine solution containing L-phenylalaninol were significantly lower than those in rats administered L-phenylalanine alone. L-phenylalaninol appears to inhibit the intestinal absorption of L-phenylalanine. This effect was more potent than that of cycloleucine. L-phenylalaninol inhibited the phenylalanine transport of everted sacs. The Km value of L-phenylalanine was 3.44 X 10(-3) M and the Ki value of L-phenylalaninol was 7.69 M 10(-3) M from Lineweaver-Burk plots. From these two curves, it appeared that L-phenylalaninol may competitively inhibit the intestinal transport of L-phenylalanine. The effects of L-phenylalanine, L-phenylalaninol and cycloleucine on the urinary excretions of Na+ and K+ in rats were also examined. Potassium excretion which increased on oral administration of L-phenylalanine, was suppressed by the administration of L-phenylalaninol but not administration of cycloleucine. L-phenylalaninol alone enhanced Na+ excretion in urine. These results confirmed that L-phenylalaninol shows inhibitory effects as potent as those of cycloleucine on the intestinal absorption of L-phenylalanine.

The effects of l-phenylalanine and phenylpyruvate on glycolysis in rat cerebral cortex

The effects of l-phenylalanine and phenylpyruvate on glycolysis in rat cerebral cortex

Electroencephalographic effects of L-phenylalanine in the cat.

THE inherited biochemical defect of the inability to oxidize phenylalanine to tyrosine and the consequent elevation of phenylalanine levels in blood and urine has long been known in phenylketonuria. 1 However, the pathogenetic mechanisms of the cerebral abnormality are as yet unclear. The abnormal metabolites of phenylalanine in phenylketonuria have been shown in vitro to inhibit the enzymes dihydroxyphenylalanine (DOPA), 5-hydroxytryptophan, and glutamic acid decarboxylases. 2-5 Christensen 6 suggested that high levels of one or more amino acids have the effect of preventing the cell from capturing other amino acids or utilizing them. Phenylalanine has been demonstrated in vivo to interfere with the intracellular accumulation of tyrosine. 7 Others have described structural defects of myelin in the brains of phenylketonuric patients. 8-11 and the lowering of the cerebroside content of the white matter. 12 The chronic effects of 1-phenylalanine on the central nervous system have been studied experimentally. Retardation

Effects of L-Phenylalanine and Sodium Phenylpyruvate on the Formation of Melanin from L-Tyrosine in Melanoma

L-PHENYLALANINE inhibits the enzymatic oxidation of L-tyrosine by tyrosinase from mushrooms1 and from Harding-Passey mouse melanoma2. This evidence indicates that the high blood concentration of L-phenylalanine found in phenylketonuria might be largely responsible for the reduced pigmentation associated with this disease1,2. This explanation would be more acceptable if it could actually be shown that L-phenylalanine inhibits the formation of melanin3. Moreover, as phenylpyruvic acid is also found in the blood of phenylketonuria patients it was of interest to see whether this substance can affect formation of melanin. The present communication reports the effects of these aromatic acids on both the enzymatic activity of tyrosinase and the conversion of L-tyrosine to melanin.