Search results for "AMINO ACID"

Melatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Function.

2021

This study was funded by grants from the Ministerio de Economia, Industria y Competitividad y por el Fondo de Desarrollo Regional FEDER, Spain nº SAF2013-49019, SAF2017-85903-P, and from the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (P07- CTS- 03135, P10- CTS- 5784, and CTS- 101), Spain. J.F. and L.M. have FPU fellowships from the Ministerio de Educación Cultura y Deporte, Spain. C.R.S. was a schorlarship holder from the Plan Propio de Investigación of the University of Granada.

Evaluation of an amino acid residue critical for the specificity and activity of human Gb3/CD77 synthase

2016

Human Gb3/CD77 synthase (α1,4-galactosyltransferase) is the only known glycosyltransferase that changes acceptor specificity because of a point mutation. The enzyme, encoded by A4GALT locus, is responsible for biosynthesis of Gal(α1–4)Gal moiety in Gb3 (CD77, Pk antigen) and P1 glycosphingolipids. We showed before that a single nucleotide substitution c.631C > G in the open reading frame of A4GALT, resulting in replacement of glutamine with glutamic acid at position 211 (substitution p. Q211E), broadens the enzyme acceptor specificity, so it can not only attach galactose to another galactose but also to N-acetylgalactosamine. The latter reaction leads to synthesis of NOR antigens, which are…

Role of AxyZ Transcriptional Regulator in Overproduction of AxyXY-OprZ Multidrug Efflux System in Achromobacter Species Mutants Selected by Tobramycin

2017

ABSTRACT AxyXY-OprZ is an RND-type efflux system that confers innate aminoglycoside resistance to Achromobacter spp. We investigated here a putative TetR family transcriptional regulator encoded by the axyZ gene located upstream of axyXY-oprZ . An in-frame axyZ gene deletion assay led to increased MICs of antibiotic substrates of the efflux system, including aminoglycosides, cefepime, fluoroquinolones, tetracyclines, and erythromycin, indicating that the product of axyZ negatively regulates expression of axyXY-oprZ . Moreover, we identified an amino acid substitution at position 29 of AxyZ (V29G) in a clinical Achromobacter strain that occurred during the course of chronic respiratory tract…

Sterols in human milk during lactation: bioaccessibility and estimated intakes.

2018

Human milk (HM) is the exclusive food during the first 4–6 months of an infant's life. Breastfeeding has been related to significant health benefits for infants, and hence it is of interest to study the bioactive compounds present in HM, such as sterols (cholesterol being the most abundant). The aim of this study was to determine the contents of sterols (cholesterol, desmosterol, lathosterol, lanosterol, campesterol, stigmasterol and β-sitosterol) in 10 pools of colostrum, transitional milk, and 1, 3 and 6 month HM obtained from Spanish volunteers from two different geographical areas (coastal and central) and to estimate the intake and bioaccessibility (BA) of sterols in order to ascertain…

Molecular diagnosis of PIK3CA-related overgrowth spectrum (PROS) in 162 patients and recommendations for genetic testing.

2017

Postzygotic activating mutations of PIK3CA cause a wide range of mosaic disorders collectively referred to as PIK3CA-related overgrowth spectrum (PROS). We describe the diagnostic yield and characteristics of PIK3CA sequencing in PROS. We performed ultradeep next-generation sequencing (NGS) of PIK3CA in various tissues from 162 patients referred to our clinical laboratory and assessed diagnostic yield by phenotype and tissue tested. We identified disease-causing mutations in 66.7% (108/162) of patients, with mutant allele levels as low as 1%. The diagnostic rate was higher (74%) in syndromic than in isolated cases (35.5%; P = 9.03 × 10−5). We identified 40 different mutations and found stro…

Effects of the flavonol quercetin and α-linolenic acid on n-3 PUFA status in metabolically healthy men and women: a randomised, double-blinded, place…

2017

AbstractIncreased dietary intake and tissue status of the long-chainn-3 PUFA, EPA and DHA, is associated with cardiovascular benefits. Epidemiological and animal studies suggest that concomitant nutritive intake of flavonoids may increase the conversion ofα-linolenic acid (ALA) to longer-chainn-3 fatty acids EPA and DHA. We investigated the effects of increased ALA intake on fatty acid composition of serum phospholipids and erythrocytes in metabolically healthy men and women and whether fatty acid profiles and ALA conversion were affected by regular quercetin intake or sex. Subjects (n74) were randomised to receive at least 3·3 g/d ALA with either 190 mg/d quercetin (ALA+quercetin) or place…

Interactive effects of aging and aerobic capacity on energy metabolism-related metabolites of serum, skeletal muscle, and white adipose tissue

2021

ABSTRACTAerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging and their interaction on metabolism, we utilized rat models of low and high intrinsic aerobic capacity (LCRs/HCRs) and assessed the metabolomics of serum, muscle, and white adipose tissue (WAT). We compared LCRs and HCRs at two time points: Young rats were sacrificed at 9 months, and old rats were sacrificed at 21 months. Targeted and semi-quantitative metabolomics analysis was performed on ultra-pressure Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS)…

Sodium functions as a negative allosteric modulator of the oxytocin receptor

2017

Abstract The oxytocin receptor, a class A G protein coupled receptor (GPCR), is essentially involved in the physiology of reproduction. Two parameters are crucially important to support high-affinity agonist binding of the receptor: Mg2+ and cholesterol, both acting as positive modulators. Using displacement assays with a high-affinity fluorescent antagonist (OTAN-A647), we now show that sodium functions as a negative allosteric modulator of the oxytocin receptor. In membranes from HEK293 cells stably expressing the oxytocin receptor, oxytocin binding occurred with about 15-fold lower affinity when sodium chloride was increased from 0 to 300 mM, whereas antagonist binding remained largely u…

The endocannabinoid-alcohol crosstalk: Recent advances on a bi-faceted target

2018

Increasing evidence has focusesed on the endocannabinoid system as a relevant player in the induction of aberrant synaptic plasticity and related addictive phenotype following chronic excessive alcohol drinking. In addition, the endocannabinoid system is implicated in the pathogenesis of alcoholic liver disease. Interestingly, whereas the involvement of CB1 receptors in alcohol rewarding properties is established, the central and peripheral action of CB2 signalling is still to be elucidated. This review aims at giving the input to deepen knowledge on the role of the endocannabinoid system, highlighting the advancing evidence that suggests that CB1 and CB2 receptors may play opposite roles i…

2019

Abstract Tyrosine nitration is a post-translational protein modification relevant to various pathophysiological processes. Chemical nitration procedures have been used to generate and study nitrated proteins, but these methods regularly lead to modifications at other amino acid residues. A novel strategy employs a genetic code modification that allows incorporation of 3-nitrotyrosine (3-NT) during ribosomal protein synthesis to generate a recombinant protein with defined 3-NT-sites, in the absence of other post-translational modifications. This approach was applied to study the generation and stability of the 3-NT moiety in recombinant proteins produced in E.coli. Nitrated alpha-synuclein (…