Absorption and Metabolism of Amino Acids Studied
Friedman Mendel in Absorption and Utilization of Amino Acids, 2019
This chapter presents results of the in vitro and in vivo absorption and metabolic studies with amino acids in parallel to each other. It discusses models for description and evaluation of the experimental results. The chapter examines the concept of an oscillatory steady state and a technique for explicit modeling and models for transport of amino acids and protein synthesis proposed for simulating complex real systems in absorption and utilization of amino acids. The role of the amino acid side chain in influx across the mucosal membranes has been examined directly for Glycine, Alanine, Valine, Leucine, and Phenylalanine. The results strongly suggest that the affinity for binding increases with increasing hydrophobicity of the side chain. The simplest model to evaluate intestinal transport processes is that which uses Vmax and Kt parameters in order to describe the saturation effect of increasing substrate concentration upon the initial velocities of the process.
Phenylketonuria
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Phenylketonuria (PKU ) is transmitted by an autosomal recessive gene on chromosome 12q22–24.1. The most important and sometimes the only manifestation of PKU is mental impairment. PKU infants appear normal at birth. Impaired mental development may not be evident for months. Vomiting may be a prominent early symptom. The gene coding for phenylalanine hydroxylase has been identified and found to have 13 exons on chromosome 12, and a large number of mutations have been identified. Restriction fragment length polymorphism exists in or near the phenylalanine hydroxylase gene that permits assessment of the transmission of alleles within a family. Expression of the mutant genes and assessment of enzyme activity in vitro has permitted correlations of phenotype with genotype. The primary effect of mutation in the gene is defective activity of the enzyme.
Amino Acids and Their Functions
Thomas Millar in Biochemistry Explained, 2018
This chapter aims to understand the general structure of amino acid, and examines special functions of amino acids and structural relationships between amino acids. The name amino acid suggests that the structures have an amine and an acid group. Indeed this is true; amino acids have an amino group and a carboxylic acid. The most important reaction amino acids can undertake is the formation of an amide bond. This forms between an amine group and an acid group and water is removed. An amide bond formed between 2 amino acids is given a special name – a peptide bond. Proteins and peptides are formed from a string of amino acids linked together by amide bonds. Some people lack phenylalanine hydroxylase and cannot make tyrosine. They therefore end up with an excess of phenylalanine which is excreted into the urine after being modified into a ketone.
The failure of L-phenylalanine and UVA in the treatment of vitiligo
Published in Journal of Dermatological Treatment, 1996
Sixteen patients with generalized vitiligo were treated with oral L-phenylalanine and UVA (PAUVA). The patients were treated twice weekly for six months, taking 50 mg/kg body weight of phenylalanine 45 minutes before exposure to UVA radiation. The UVA dose was carefully graduated and increased in increments of 30–50% every third treatment according to the patient's response. Another ten patients with generalized vitiligo were treated with UVA alone and acted as a control group. None of the patients in either group showed significant improvement. No side-effects were observed during the study.
Synthesis and biological activity of novel thiourea derivatives as carbonic anhydrase inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2015
Neslihan Korkmaz, Oday A. Obaidi, Murat Senturk, Demet Astley, Deniz Ekinci, Claudiu T. Supuran
A new series of chiral thiourea derivatives (5a–5c) and thiourea containing benzimidazole moieties (9b–9e) were synthesized from different amino acids (l-valine, l-isoleucine, l-methionine, l-phenylalanine, and d-phenylglycine). The compounds were characterized and tested against the two most studied members of the pH regulatory enzyme family, carbonic anhydrase (CA, EC 4.2.1.1). KI values of the novel compounds were measured in the range of 3.4–73.6 μM for hCA I isozyme and 8.7–1.44.2 μM for hCA II isozyme, respectively. Phenol was also tested as standard in order to understand the structure activity relationship and the clinically used sulfonamide acetazolamide was tested for comparison reasons. All of the compounds exhibited competitive inhibition with 4-nitrophenylacetate as substrate.
Understanding drug-excipient compatibility: Oxidation of compound A in a solid dosage form
Published in Pharmaceutical Development and Technology, 2009
Yongmei Wu, Mandar Dali, Abhishek Gupta, Krishnaswamy Raghavan
Drug-excipient compatibility studies lay the foundation for designing a chemically stable formulation for clinical and commercial development. This article describes the investigation of oxidative degradation encountered with compound A (a phenylalanine-drug complex) in a capsule dosage form. Two wet- granulation capsule formulations (2.5-mg and 25-mg strengths) were developed using excipients that showed satisfactory stability from initial drug-excipient compatibility studies. Both capsule strengths were chemically stable at 50°C (closed) for at least 18 weeks, but they showed discoloration. The 2.5-mg capsule exhibited degradation after four weeks at 40°C/75%RH (open) besides discoloration. LC/MS analysis indicated that the degradants were oxidation products of the parent compound. Oxidation of compound A was investigated by forced degradation with peroxide, use of isotopically labeled water (H218O) to study the source of oxygen, and use of different antioxidants to mitigate oxidation. Excipient(s) responsible for oxidation and discoloration were identified through extended and modified excipient compatibility studies. The discoloration was indicative of Maillard reaction occurring between a reducing sugar impurity from microcrystalline cellulose and L-phenylalanine in the drug complex. Reactive oxidative species generated by this reaction is postulated to cause oxidation of compound A.
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