title: Dose-Dependent Effects of L-Arginine on PROP Bitterness Intensity and Latency and Characteristics of the Chemical Interaction between PROP and L-Arginine.
abstract: Genetic variation in the ability to taste the bitterness of 6-n-propylthiouracil (PROP) is a complex trait that has been used to predict food preferences and eating habits. PROP tasting is primarily controlled by polymorphisms in the TAS2R38 gene. However, a variety of factors are known to modify the phenotype. Principle among them is the salivary protein Ps-1 belonging to the basic proline-rich protein family (bPRP). Recently, we showed that oral supplementation with Ps-1 as well as its related free amino acids (L-Arg and L-Lys) enhances PROP bitterness perception, especially for PROP non-tasters who have low salivary levels of Ps-1. Here, we show that salivary L-Arg levels are higher in PROP super-tasters compared to medium tasters and non-tasters, and that oral supplementation with free L-Arg enhances PROP bitterness intensity as well as reduces bitterness latency in a dose-dependent manner, particularly in individuals with low salivary levels of both free L-Arg and Ps-1 protein. Supplementation with L-Arg also enhanced the bitterness of caffeine. We also used 1H-NMR spectroscopy and quantum-mechanical calculations carried out by Density Functional Theory (DFT) to characterize the chemical interaction between free L-Arg and the PROP molecule. Results showed that the -NH2 terminal group of the L-ArgH+ side chain interacts with the carbonyl or thiocarbonyl groups of PROP by forming two hydrogen bonds with the resulting charged adduct. The formation of this PROP•ArgH+ hydrogen-bonded adduct could enhance bitterness intensity by increasing the solubility of PROP in saliva and its availability to receptor sites. Our data suggest that L-Arg could act as a 'carrier' of various bitter molecules in saliva.
authors.affiliation: Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Monserrato, CA, Italy.
authors.forename: Melania
authors.initials: M
authors.lastname: Melis
authors.affiliation: Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari, Monserrato, CA, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Arca
authors.affiliation: Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari, Monserrato, CA, Italy.
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Aragoni
authors.affiliation: Department of Life and Environment Sciences, Macrosection of Biomedicine, University of Cagliari, Monserrato, CA, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cabras
authors.affiliation: Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari, Monserrato, CA, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Caltagirone
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry, Catholic University, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Castagnola
authors.affiliation: Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Monserrato, CA, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Crnjar
authors.affiliation: Department of Life and Environment Sciences, Macrosection of Biomedicine, University of Cagliari, Monserrato, CA, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Messana
authors.affiliation: Department of Food Science, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, New Jersey, United States of America.
authors.forename: Beverly J
authors.initials: BJ
authors.lastname: Tepper
authors.affiliation: Department of Biomedical Sciences, Section of Physiology, University of Cagliari, Monserrato, CA, Italy.
authors.forename: Iole
authors.initials: I
authors.lastname: Tomassini Barbarossa
mesh_terms: D000328:Adult; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D002110:Caffeine / Q000737:chemistry; D002256:Carbonic Anhydrases / Q000235:genetics / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005518:Food Preferences / Q000187:drug effects; D005838:Genotype; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010641:Phenotype; D011441:Propylthiouracil / Q000737:chemistry*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology; D012463:Saliva / Q000737:chemistry*; D012995:Solubility; D013649:Taste / Q000187:drug effects* / Q000502:physiology; D055697:Taste Perception / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D055815:Young Adult; D000098706:Taste Receptors, Type 2
chemical_list: D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D002110:Caffeine; D011441:Propylthiouracil; D001120:Arginine; D002256:Carbonic Anhydrases; C477051:carbonic anhydrase VI