High Phenylalanine Concentrations Research Articles

Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria.

Biogenic amines synthesis in phenylketonuria (PKU) patients with high phenylalanine (Phe) concentration is thought to be impaired due to inhibition of tyrosine and tryptophan hydroxylases and competition with amino acids at the blood-brain barrier. Dopamine and serotonin deficits might explain brain damage and progressive neuropsychiatric impairment in adult PKU patients. Ten early treated adult PKU patients (mean age 38.2 years) and 15 age-matched controls entered the study. Plasma and cerebrospinal fluid (CSF) Phe, 5-hydroxyindoleacetic acid (5-HIAA), 5-hydroxytryptophan (5-HTP), 3,4-dihydroxy-l-phenylalanine (l-DOPA) and homovanillic acid (HVA) were analyzed. Voxel-based morphometry statistical nonparametric mapping was used to test the age-corrected correlation between gray matter atrophy and CSF biogenic amines levels. 5-HIAA and 5-HTP were significantly reduced in PKU patients compared to controls. Significant negative correlations were found between CSF 5-HIAA, HVA, and 5-HTP and Phe levels. A decrease in 5-HIAA and 5-HTP concentrations correlated with precuneus and frontal atrophy, respectively. Lower HVA levels correlated with occipital atrophy. Biogenic amines deficits correlate with specific brain atrophy patterns in adult PKU patients, in line with serotonin and dopamine projections. These findings may support a more rigorous Phe control in adult PKU to prevent neurotransmitter depletion and accelerated brain damage due to aging.

Omega-3 Uzun Zincirli Çoklu Doymamış Yağ Asitleri ve Fenilketonüri

Beyin, retina ve diğer sinir dokuları uzun zincirli çoklu doymamış yağ asitlerinden (UZÇDYA) zengindir. Birçok klinik ve epidemiyolojik çalışma ile omega-3 UZÇDYA’ların çocukluk çağındaki nöral gelişim üzerine olumlu etkileri olduğu kanıtlanmıştır. Uzun zincirli ÇDYA’lar, diyetle alımları yeterli olduğu sürece temel elzem yağ asitlerinden endojen olarak sentezlenebilirler. Aynı zamanda, et, balık, yumurta, karaciğer ve süt ürünleri gibi proteinden zengin besinler eikosapentaenoik asit (EPA) ve dokosaheksaenoik asit (DHA) gibi UZÇDYA’ların en belirgin diyetsel kaynaklarıdır. Bununla birlikte, klasik fenilketonürili (FKÜ) hastalar yüksek plazma fenilalanin konsantrasyonları ve nörolojik hasarı önlemek için diyet protein alımında sıkı ve ömür boyu süren bir sınırlamaya ihtiyaç duyarlar. Bu katı metabolik kontrol sadece düşük miktarda vitamin ve mineral sağlamakla kalmaz, genellikle doymuş yağ asitleri ve ÇDYA’ların da düşük miktarda alınmasına neden olur. Bu nedenle, FKÜ’lü hastalar sağlıklı kontrollerle karşılaştırıldığında UZÇDYA alımları daha az olmakta ve daha düşük plazma ve eritrosit UZÇDYA konsantrasyonlarına sahip olmaktadırlar. Bebeklik ve çocukluk döneminde, UZÇDYA’lar normal nörogelişim için önemlidir. Yetersizliği, okul öncesi ve okul çağındaki FKÜ’lü çocuklarda erken dönemde saptanabilen merkezi sinir sistemi işlev bozukluklarına katkıda bulunabilir. Ayrıca, UZÇDYA yetersizliğinin kronik nörolojik, inflamatuvar ve metabolik bozukluklara neden olabileceği de ileri sürülmektedir. Diğer taraftan, randomize kontrollü çalışmalardan elde edilen veriler, FKÜ’lü hastalardaki UZÇDYA durumunun diyet takviyesi ile iyileştirilebileceğini önermektedir. Bu derleme yazıda, fenilalaninden kısıtlı diyetler ile UZÇDYA arasındaki ilişki incelenmiş ve FKÜ’lü hastalar için UZÇDYA’ların önemi ele alınmıştır.

Effects of Solid-State Fermentation and the Potential Use of Cassava By-products as Fermented Food

By-products such as cassava bagasse and leaves are discarded though they contain high amounts of carbohydrates, proteins, fat and minerals. The application of solid-state fermentation (SSF) to substrates containing these by-products could improve the bioavailability of nutrients while reducing the amounts of anti-nutritive factors such as cyanide. To evaluate the possibility of using by-products from cassava some techniques, such as colorimetric methods, gas chromatography and high performance of liquid chromatography were applied to evaluate the total cyanide, carbohydrate contents, to characterize the fatty acid profiles, and estimate the essential amino acids after the fermentation process. After the SSF process, the cyanide content was significantly decreased. The profile of essential amino acids showed high concentrations of histidine, isoleucine, valine, methionine and phenylalanine. Some important unsaturated fatty acids were found, such as linoleic acid (18:29,12); α-linolenic acid (18:39,12,15); 11-eicosenoic acid (20:1) and 13,16-docosadienoic acid (22:2). The evaluation of the protein quality showed a significant increase in its bioavailability. The results support the conclusion that currently not used agricultural by-products could become sources of food that provide important quantities of essential nutrients.

AMP-activated protein kinase activation in mediating phenylalanine-induced neurotoxicity in experimental models of phenylketonuria.

Phenylketonuria (PKU), one of the most prevalent autosomal recessive disorders of amino acid metabolism, is characterized by abnormal accumulation of phenylalanine, which can lead to intellectual disability. The main pathologic changes in the central nervous system of untreated phenylketonuric patients are reductions in the number of axons, dendrites, and synapses in the brain. Such alterations are thought to be mainly associated with the toxic effects caused by phenylalanine. However, the underlying molecular mechanisms have not been fully elucidated. The present study shows that a high concentration of phenylalanine remarkably inhibited neuronal neurite formation in vitro. Interestingly, AMP-activated protein kinase (AMPK), the energy status sensor, was activated in cultured cerebral cortical neurons upon phenylalanine treatment. Pretreatment with an AMPK inhibitor ameliorated the reduction of neurite formation caused by phenylalanine. In addition, the levels of the phosphorylated AMPK, the active form of AMPK, were significantly higher in the cerebral cortices of PKU mice with elevated phenylalanine levels in this brain region compared to those in wild-type control mice, whereas the density of dendritic spines on basal secondary dendrites of pyramidal neurons in prefrontal cortices of PKU mice was significantly decreased. Collectively, these findings indicate that AMPK activation is a key event in impaired neuronal dendritic development in PKU and consequently, a potential therapeutic target for developing neuroprotective strategies against phenylalanine-evoked brain injury in PKU.

Phenylalanine Increases Membrane Permeability.

Biological membranes are a crucial aspect of living systems, controlling the organization and distribution of different chemical components. Control of membrane permeability is especially important for processes such as electron transport in metabolism and signal propagation in nerve cells. In this work, we show that the amino acid phenylalanine produces increased membrane permeability, which is likely responsible for some of the deleterious symptoms associated with high biological phenylalanine concentrations that occur with the genetic disorder phenylketonuria.

Dynamics of hyperphenylalaninemia and intellectual outcome in teenagers with phenylketonuria.

Insufficient treatment adherence after early childhood is frequently observed in patients with phenylketonuria. Assessment of these individuals' long-term metabolic control could enable early detection of the risk of intellectual deterioration resulting from high blood phenylalanine concentration. However, the predictive value of specific parameters related to individual dynamics of hyperphenylalaninemia is not clear. Here, we assessed the impact of blood phenylalanine fluctuations during the first 12 years of life on cognitive outcome in early and continuously treated teenagers with phenylketonuria. We have analyzed a total of 5141 results of blood phenylalanine measurements in 32 patients. The phenylalanine levels of these patients were usually acceptable during their early childhood, but the control of hyperphenylalaninemia worsened and the average treatment adherence dropped to 40% during the late primary school. Our analysis revealed a strong association between the Wechsler intelligence verbal scores and the mean of the yearly means of phenylalanine concentrations (r=-0.62). The correlations of IQ scores with median phenylalanine concentrations and the variability of blood phenylalanine levels gave weaker associations. The Wechsler verbal scores were also strongly correlated with the treatment adherence level during preschool and late primary school (r=0.61 and 0.72). The mean of the yearly means of blood phenylalanine concentrations appears to be a better predictor of cognitive outcome in children with phenylketonuria than other parameters related to phenylalanine fluctuations. The percentage of acceptable phenylalanine levels below 50-60% should be regarded as a "red flag" due to the risk of intellectual deterioration in patients.

Neurological and Neuropsychological Problems in Tyrosinemia Type I Patients.

Clinically, Hereditary Tyrosinemia type I (HTI) is especially characterized by severe liver dysfunction in early life. However, recurrent neurological crises are another main finding in these patients when they are treated with a tyrosine and phenylalanine restricted diet only. This is caused by the accumulation of δ-aminolevulinic acid due to the inhibitory effect of succinylacetone on the enzyme that metabolizes δ-aminolevulinic acid. Due to the biochemical and clinical resemblance of these neurological crises and acute intermittent porphyria, this group of symptoms in HTI patients is mostly called porphyria-like-syndrome. The neurological crises in HTI patients disappeared after the introduction of treatment with 2-(2 nitro-4-3 trifluoro-methylbenzoyl)-1, 3-cyclohexanedione (NTBC). However, if NTBC treatment is stopped for a while, severe neurological dysfunction will reappear.If NTBC treatment is started early and given continuously, all clinical problems seem to be solved. However, recent research findings indicate that HTI patients have a non-optimal neurocognitive outcome, showing (among others) a lower IQ and impaired executive functioning and social cognition. Unfortunately the exact neuropsychological profile of these HTI patients is not known yet, neither are the exact pathophysiological mechanisms underlying these impairments. It may be hypothesized that the biochemical changes such as high blood tyrosine or low blood phenylalanine concentrations are important in this respect, but an direct toxic effect of NTBC or production of toxic metabolites (that previously characterized the disease before introduction of NTBC) cannot be excluded either. This chapter discusses the neurological and neuropsychological symptoms associated with HTI in detail. An extended section on possible underlying pathophysiological mechanisms of such symptoms is also included.

Validation of amino-acids measurement in dried blood spot by FIA-MS/MS for PKU management

ObjectivesPhenylketonuria (PKU) is a metabolic disorder leading to high concentrations of phenylalanine (Phe) and low concentrations of tyrosine (Tyr) in blood and brain that may be neurotoxic. This disease requires a regular monitoring of plasma Phe and Tyr as well as branched-chain amino-acids concentrations to adapt the Phe-restricted diet and other therapy that may be prescribed in PKU. We validated a Flow Injection Analysis tandem Mass Spectrometry (FIA-MS/MS) to replace the enzymatic method routinely used for neonatal screening in order to monitor in parallel to Phe, Tyr and branched-chain amino-acids not detected by the enzymatic method. Design and methodsWe ascertained the performances of the method: linearity, detection and quantification limits, contamination index, accuracy. We cross validated the FIA-MS/MS and enzymatic methods and we evaluated our own reference ranges to monitor Phe, Tyr, Leu, Val on 59 dried blood spots of normal controls. We also evaluated Tyr, Leu and Val concentrations in PKU patients to detect some potential abnormalities, not evaluated by the enzymatic method. ResultsWe developed a rapid method with excellent performances including precision and accuracy <15%. We noted an excellent correlation of Phe concentrations between FIA-MS/MS and enzymatic methods (p<0.0001) based on our database which are similar to references ranges published. We observed that 50% of PKU patients had lower concentrations of Tyr, Leu and/or Val that could not be detected by the enzymatic method. ConclusionBased on laboratory accreditation recommendations, we validated a robust, rapid and reliable FIA-MS/MS method to monitor plasma Phe concentrations but also Tyr, Leu and Val concentrations, suitable for PKU management. We evaluated our own reference ranges of concentration for a routine application of this method.

Clinical characteristics and intervention in maternal phenylketonuria

Maternal phenylketonuria(MPKU) is a syndrome caused by high phenylalanine concentrations in serum of pregnant women with phenylketonuria.MPKU results in neonatal microcephaly, facial dysmorphism, congenital heart defects, mental retardation, intrauterine growth restriction, behavior and emotional problems.To control serum Phe level of pregnant phenylketonuria women and maintain Phe concentration between 120 to 360 μmol/L will prevent offspring poor outcomes such as intellectual disabilities and microcephaly.Three level interventions are best ways in MPKU management. Key words: Maternal Hyperphenylalaninemia; Phenylalanine; Dysmorphism

Postprandial Levels of Branch Chained and Aromatic Amino Acids Associate with Fasting Glycaemia.

High fasting plasma concentrations of isoleucine, phenylalanine, and tyrosine have been associated with increased risk of hyperglycaemia and incidence of type 2 diabetes. Whether these associations are diet or metabolism driven is unknown. We examined how the dietary protein source affects the postprandial circulating profile of these three diabetes associated amino acids (DMAAs) and tested whether the postprandial DMAA profiles are associated with fasting glycaemia. We used a crossover design with twenty-one healthy individuals and four different isocaloric test meals, containing proteins from different dietary sources (dairy, fish, meat, and plants). Analysis of the postprandial DMAAs concentrations was performed using targeted mass spectrometry. A DMAA score was defined as the sum of all the three amino acid concentrations. The postprandial area under the curve (AUC) of all the three amino acids and the DMAA score was significantly greater after intake of the meal with dairy protein compared to intake of the three other meals. The postprandial AUC for the DMAA score and all the three amino acids strongly associated with fasting glucose level and insulin resistance. This indicates the importance of the postprandial kinetics and metabolism of DMAAs in understanding the overall association between DMAAs and glycaemia.

Effect of experimental phenylketonuria on the development of skin of prenatel and newborn fetuses.

Phenylketonuria (PKU) is a genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. The disease results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine to tyrosine. The present work studied the Effect of experimental phenylketonuria on the development of skin of prenatel and newborn fetuses.The disease was induced in pregnant rats by daily intragastric administration of 30 mg. DL-a-methylphenylalanine/kg body weight plus 60 mg/kg body weight at 12 h intervals throughout pregnancy till parturition. Treatment with alpha-methylphenylalanine/phenylalanine resulted in significant decrease of accumulated body weight gain during pregnancy as well as exhibited marked growth retardation of prenatal fetuses and delivered newborn. The growth retarded fetuses was manifested by decreased body weight, malformed both fore -& hind limb, oedematous skin & superficial hematomas widely spreads in different parts of the body. Vibrissae skin hair were characterized by curved free ends as well as reduction of their size and length. Cornification was retarded . The epidermis attained a considerable thinning with delayed differentiation of epidermal cell layers.The growing hair follicles lacked normal characteristic appearance. These results suggested that exposure of the fetus to high plasma concentrations of phenylalanine caused a delay in the biochemical maturation of the fetal rat.

Phenylketonuria: Direct and indirect effects of phenylalanine

High phenylalanine concentrations in the brain due to dysfunctional phenylalanine hydroxylase (Pah) are considered to account for mental retardation in phenylketonuria (PKU). In this study, we treated hippocampal cultures with the amino acid in order to determine the role of elevated levels of phenylalanine in PKU-related mental retardation. Synapse density and dendritic length were dramatically reduced in hippocampal cultures treated with phenylalanine. Changes in cofilin expression and phosphorylation status, which were restored by NMDA, as well as reduced activation of the small GTPase Rac1, likely underlie these structural alterations. In the Pahenu2 mouse, which carries a mutated Pah gene, we previously found higher synaptic density due to delayed synaptic pruning in response to insufficient microglia function. Microglia activity and C3 complement expression, both of which were reduced in the Pahenu2 mouse, however, were unaffected in hippocampal cultures treated with phenylalanine. The lack of a direct effect of phenylalanine on microglia is the key to the opposite effects regarding synapse stability in vitro and in the Pahenu2 mouse. Judging from our data, it appears that another player is required for the inactivation of microglia in the Pahenu2 mouse, rather than high concentrations of phenylalanine alone. Altogether, the data underscore the necessity of a lifelong phenylalanine-restricted diet.

Triterpene and Flavonoid Biosynthesis and Metabolic Profiling of Hairy Roots, Adventitious Roots, and Seedling Roots of Astragalus membranaceus.

Astragalus membranaceus is an important traditional Chinese herb with various medical applications. Astragalosides (ASTs), calycosin, and calycosin-7-O-β-d-glucoside (CG) are the primary metabolic components in A. membranaceus roots. The dried roots of A. membranaceus have various medicinal properties. The present study aimed to investigate the expression levels of genes related to the biosynthetic pathways of ASTs, calycosin, and CG to investigate the differences between seedling roots (SRs), adventitious roots (ARs), and hairy roots (HRs) using quantitative real-time polymerase chain reaction (qRT-PCR). qRT-PCR study revealed that the transcription level of genes involved in the AST biosynthetic pathway was lowest in ARs and showed similar patterns in HRs and SRs. Moreover, most genes involved in the synthesis of calycosin and CG exhibited the highest expression levels in SRs. High-performance liquid chromatography (HPLC) analysis indicated that the expression level of the genes correlated with the content of ASTs, calycosin, and CG in the three different types of roots. ASTs were the most abundant in SRs. CG accumulation was greater than calycosin accumulation in ARs and HRs, whereas the opposite was true in SRs. Additionally, 40 metabolites were identified using gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS). Principal component analysis (PCA) documented the differences among SRs, ARs, and HRs. PCA comparatively differentiated among the three samples. The results of PCA showed that HRs were distinct from ARs and SRs on the basis of the dominant amounts of sugars and clusters derived from closely similar biochemical pathways. Also, ARs had a higher concentration of phenylalanine, a precursor for the phenylpropanoid biosynthetic pathway, as well as CG. TCA cycle intermediates levels including succinic acid and citric acid indicated a higher amount in SRs than in the others.

Protective effect of L-carnitine on Phenylalanine-induced DNA damage.

The pathogenesis and the progression of phenylketonuria (PKU), an inborn error of phenylalanine (Phe) metabolism, have been associated with oxidative damage. Moreover, it has been increasingly postulated the antioxidant properties of L-Carnitine (LC). The aim of this study was to verify the effect of LC on Phe-induced DNA damage. The in vitro effect of different concentrations of LC (15, 30, 120 and 150μM) on DNA damage-induced by high phenylalanine levels (1000 and 2500μM) was examined in white blood cells from normal individuals using the comet assay. Urinary 8-hydroxydeoguanosine (8-OHdG) levels, a biomarker of oxidative DNA damage, and plasmatic sulfhydryl content were measured in eight patients with classical PKU, under therapy with protein restriction and supplemented with a special formula containing LC, and in controls individuals. Both in vitro tested Phe concentrations (1000 and 2500μM) have resulted in DNA damage index significantly higher than control group. The in vitro co-treatment with Phe and LC reduced significantly DNA damage index when compared to Phe group. The urinary excretion of 8-OHdG and plasmatic sulfhydryl content presented similar levels in both groups analyzed (controls and treated PKU patients). In treated PKU patients, urinary 8-OHdG levels were positively correlated with blood Phe levels and negatively correlated with blood LC concentration and plasmatic sulfhydryl content. The present work yields experimental evidence that LC can reduce the in vitro DNA injury induced by high concentrations of phenylalanine, as well as, allow to hypothesize that LC protect against DNA damage in patients with PKU.

Plasma amino acid profiling of cancer patients with abnormal Savda based on high-performance liquid chromatography

ObjectiveTo investigate metabolic signatures in plasma of cancer patients with abnormal Savda using plasma-free amino acid profiles, and to evaluate the diagnostic potential of these profiles for the detection and explanation of the mechanisms of different symptoms in traditional Uyghur medicine. MethodsPlasma samples from cancer patients with abnormal Savda (n=85) or non-abnormal Savda (n=105) and a healthy control group (n=65) were analyzed using high-performance liquid chromatography (HPLC). Orthogonal projection to latent structures with discriminant analysis was used for the classification and prediction of abnormal Savda, and spectral profiles were subjected to Student's t-tests to assess statistical significance. ResultsCompared with the healthy group, the levels of aspartic acid, glutamate, glycine, histidine, arginine, threonine, alanine, proline, methionine, isoleucine, leucine and phenylalanine decreased significantly in plasma of cancer patients with abnormal Savda (all P<0.05). Serine, cystine, tyrosine, valine and lysine levels showed no significant differences (all P>0.05). Compared with non-abnormal Savda syndrome patients, abnormal Savda syndrome patients showed high concentrations of glutamate, serine, valine, isoleucine, leucine and phenylalanine (all P<0.05). The remaining plasma amino acids showed no significant differences (all P> 0.05). ConclusionPlasma-free amino acid profiling has the potential to assist in understanding and determining abnormal Savda. A HPLC-based metabonomic platform could be a powerful tool for the classification of symptoms in traditional medicine.

EPA-0451 - Phenylalanine and tyrosine concentrations in euthymic bipolar disorder

Background Individuals with bipolar disorder (BD) are differentially affected by insulin resistance. Individuals without history of mental disorder with insulin resistance usually have high peripheral concentrations of phenylalanine (PHE) and tyrosine (TYR) together. Catecholamine dysfunction is described to be a state-dependend phenomen in patients suffering from BD. Catecholamines are synthesized from essential amino acids PHE and TYR which are biotransformed to dopamine and subsequently converted to nor/adrenaline. Amino acid dysregulation may be a possible mediator of insulin resistance in BD. Patients/Methods Peripheral PHE and TYR concentrations were investigated in euthymic adults with BD. Amino acid differences between normal and overweight individuals with BD were evaluated and outcomes were correlated with the measures of glucose homeostasis. Results Mean plasma PHE to TYR ratio (PHE/TYR) was at the upper limit of the normal range in the whole sample. Enrolled subjects with PHE/TYR beyond the limits of normal exhibited the highest number of prior affective episodes. Sex-specific differences were noted as overweight BD females showed different profiles than normal-weight women. In the overweight females, PHE and TYR concentrations were significantly higher compared to normal-weight women. Significant correlations were noticed between PHE, TYR and PHE/TYR with insulin/Homeostasis Model of Assessment (HOMA)-IR in the whole sample and the subgroup of BD women. Conclusion These significant differences in gender, amino acid pathways and in correlations with immune marker as well as insulin function have not been reported previously. Taken together, increased levels of PHE in BD should be considered when adjudicating diabetes risk especially in women.

Infants with Tyrosinemia Type 1: Should phenylalanine be supplemented?

Tyrosinemia type 1 (HT1) is an inborn error of tyrosine catabolism caused by fumarylacetoacetase deficiency. Biochemically, this results in accumulation of toxic metabolites including succinylacetone. Clinically, HT1 is characterized by severe liver, kidney, and neurological problems. Treatment with NTBC and dietary restriction of tyrosine and phenylalanine have strongly improved outcome, but impaired neurocognitive development has been reported. Whether impaired neurocognitive outcome results from high blood tyrosine or low blood phenylalanine concentrations is currently unknown. In this report, two HT1 newborns, diagnosed by neonatal screening, are presented. The first patient showed low phenylalanine concentrations, growth retardation, neurological impairments, and skin problems, clearly improving after institution of phenylalanine supplementation (~30mg/kg/day) at age 6months, while both blood phenylalanine and tyrosine concentrations increased. In the second patient, phenylalanine supplementation (~20mg/kg/day) was initiated as soon as low phenylalanine concentrations were observed at age 19days. On this regimen, blood phenylalanine concentrations increased, and hypophenylalaninemia was less frequently observed than in the first patient, whereas blood tyrosine concentrations tended to increase. Clinically, no growth, neurological, or skin problems have been observed. The combination of knowledge obtained from these cases suggests that hypophenylalaninemia rather than hypertyrosinemia during the first months of life may impair neurocognitive development in young HT1 infants. Phenylalanine supplementation should really be considered in HT1 patients with consistently low blood phenylalanine concentrations during the first months of life. However, the minimal phenylalanine concentrations acceptable and the optimal phenylalanine supplementation regimen require further investigation.

Immune activation in patients with Alzheimer's disease is associated with high serum phenylalanine concentrations

BackgroundImmune activation and inflammation represent critical factors in the pathogenesis of Alzheimer's disease (AD) and are associated with increased blood concentrations of markers like neopterin and the kynurenine to tryptophan ratio (Kyn/Trp). In chronic inflammatory conditions, also increased serum phenylalanine concentrations and phenylalanine to tyrosine ratios (Phe/Tyr) were reported and could relate to neuropsychiatric symptoms. ObjectiveTo examine serum phenylalanine and tyrosine concentrations in patients with AD and to compare results to neopterin and Kyn/Trp levels. Materials and methodsSerum was collected from 43 patients with AD and concentrations of phenylalanine and tyrosine as well as neopterin, tryptophan and kynurenine were measured and Phe/Tyr and Kyn/Trp were calculated. ResultsA subgroup of AD patients presented with increased phenylalanine and Phe/Tyr concentrations, phenylalanine levels correlated with neopterin (rs=0.329), kynurenine (rs=0.352) and Kyn/Trp levels (rs=0.288; all p<0.05). There was no significant relationship between phenylalanine metabolism and cognitive ability test scores mini-mental state examination and clock drawing test. ConclusionsHigher serum phenylalanine concentrations related to immune activation are detectable in a subgroup of AD patients. The impaired conversion of phenylalanine may affect not only the production of tyrosine but also the biosynthesis of the neurotransmitters dopamine, norepinephrine and epinephrine. Further studies are justified in patients with AD to investigate a possible role of phenylalanine biochemistry in the development of neurovegetative and behavioral abnormalities.

Identification of components of Brazilian honey by 1H NMR and classification of its botanical origin by chemometric methods

The potential of NMR spectroscopy to differentiate honeys concerning to the nectar employed in its production was evaluated. The application of chemometric methods to 1H NMR spectra has allowed to discriminate the honeys produced in the state of São Paulo, being identified the signals of responsible substances for the discrimination. Application of PCA and HCA methods to 1H NMR data have resulted in the natural clustering of the samples. Wildflower honeys were characterized by higher concentration of phenylalanine and tyrosine. Citrus honeys showed higher amounts of sucrose than other compounds, while eucalyptus honeys had higher amount of lactic acid than the others. Assa-peixe honeys showed spectra similar to eucalyptus and citrus. Sugar-cane honeys showed some signals similar to eucalyptus and citrus honeys, but also showed the tyrosine and phenylalanine signals. Adulterated honeys showed 5-hydroxymethylfurfural, citric acid and ethanol signals. KNN, SIMCA and PLS-DA methods were used to build predictive models for honey classification. In the commercial honeys prediction KNN, SIMCA and PLS-DA models correctly classified 66.7; 22.2 and 72.2% of the samples, respectively.

PKU: High plasma phenylalanine concentrations are associated with increased prevalence of mood swings

In phenylketonuria, knowledge about the relation between behavior and plasma phenylalanine is scarce. The aim of this study was to determine whether high phenylalanine is associated with disturbed behavior noticed by the patient and or close environment (parents or partners). 48 early treated PKU patients (median age 8.5, range 0–35years) participated (median phenylalanine concentration in total sample 277 (range 89–1171) μmol/l; and in patients <12years 238 (range 89–521) μmol/l). After sending blood samples, patients or close environment were interviewed with a standardized questionnaire whether they noticed hyperactivity, annoying behavior, mood swings and introvert or extravert behavior. The interviewer as well as the respondents were blinded with regard to the phenylalanine concentration. Results: Patients reported less deviant behavior compared to close environment. Mood swings were positively associated with phenylalanine concentrations in the total group (P=0.039) and patients <12years (P=0.042). The relationships between temporary high phenylalanine concentrations and hyperactivity, annoying behavior, introvert and extravert behavior were not statistically significant. Conclusion: there is a positive association between phenylalanine concentrations and mood swings.