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Argininosuccinic aciduria
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Heterogeneity in the mutations responsible for deficient enzyme activity in argininosuccinic aciduria was demonstrated in complementation studies of fibroblasts of 28 patients [36], in which there was a single major complementation group, but there were 12 interallelic complementation subgroups consistent with 12 allelic mutations. The enzyme is a homotetramer in which the monomeric subunit has a molecular weight of 50 kDa [37]. Immunochemical studies of the enzyme after electrophoresis on sodium dodecylsulfate polyacrylamide gel electrophoresis revealed two bands of approximately 49 and 51 kDa in normal cells [38]. Each of 28 variants had some 49 kDa cross-reacting material (CRM). The 51-kDa band was found in only six variants in which CRM or residual enzyme activity was very high.
The Bioenergetics of Mammalian Sperm Motility
Published in Claude Gagnon, Controls of Sperm Motility, 2020
The presence of an electrophoretically unique form of lactate dehydrogenase in sperm was first recognized in extracts of human testis and spermatozoa.70,71 The enzyme has been well characterized by immunological, sequencing, and X-ray diffraction methods.72-76 The enzyme is a homotetramer of 4 LDH C subunits with a molecular weight of about 140,000. Each monomer contains 330 amino acid residues (rat and mouse). The monomers are able to form heterotetramers with the ‘A’ or ‘B’ subunits of somatic lactate dehydrogenase in vitro although such hybrids do not occur in vivo. Additional forms of the C subunit are found in spermatozoa from some infertile men.77 In evolutionary terms, the coenzyme-binding region is more conserved than the substrate-binding region between LDH-A4, LDH-B4, and LDH-C4, and ‘A’ and ‘B’ subunits are more closely related to each other than to the C subunit.78 LDH-C4 has different catalytic properties from the somatic enzymes; it is less sensitive to inhibition by lactate and more sensitive to inhibition by puruvate and can metabolize a wide range of 2-hydroxy/keto acids, including the transamination products of the branched chain amino acids.79 This may be important in the metabolic interaction between the Sertoli cells and the germ cells42 and provides a convenient means to assay the enzyme in the presence of the somatic isoenzymes. LDH-C4 can also accept NADPH as a cofactor.80
Local Anesthetics
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Elena González Burgos, Luis Luis García-García, M. Pilar Gómez-Serranillos, Francisca Gómez Oliver
The α-subunit has a homotetrameric structure having four clearly differentiated domains (DI–DIV). Each one of the four domains is in turn conformed by six transmembrane homologous, but not identical, α-helices segments (S1–S6) (Fig. 15.5A). In each domain, segments S1–S4 are known as the “voltage sensor domains (VSDs).” Nonetheless, the S4 segments seem to be most crucial due to their primary structure consisting of a sequence of three amino acid residues, such as arginines and lysines, that positively charged, are repeated with an in between separation by two nonpolar amino acid residues. The membrane depolarization drives the S4 segments outward opening the pore (Patino and Isom, 2010; Payandeh et al., 2011).
Searching for effective antiviral small molecules against influenza A virus: A patent review
Published in Expert Opinion on Therapeutic Patents, 2021
Tiziana Ginex, F. Javier Luque
NA assembles as a homotetramer, each monomer consisting of four structural domains: the cytoplasmic tail, the transmembrane region, the stalk and the catalytic (sialidase) domain (Figure 3). Arg118, Asp151, Arg152, Arg224, Glu276, Arg292, Arg371, and Tyr406 shape the catalytic binding site. The FDA-approved NA inhibitors zanamivir and oseltamivir block sialidase activity by targeting the SA binding site in the catalytic head domain of the protein (Figure 3). Mutations near this site are quite frequent and can affect the activity of NA inhibitors. In this regard, of great importance are the H274Y and the E119G mutations, which induce resistance to oseltamivir and zanamivir, respectively [60,61]. Detailed reports about influenza resistance to NA inhibitors can be found elsewhere [62,63]. Here, attention will be focused on the most relevant NA inhibitors developed in the last years, especially regarding the chemical modifications introduced in the reference compounds, zanamivir and oseltamivir.
Sense and nonsense concerning biotin interference in laboratory tests
Published in Acta Clinica Belgica, 2022
Alena Moerman, Joris R. Delanghe
In other words, the usage of biotin is very popular and widely distributed in modern immunoassays. Its usefulness lies in the fact that it is a small molecule (244,31 g/mol) that binds with exceptional strength and specificity to streptavidin. The latter is an 56 kDa homotetramer, able to bind up to 4 biotin molecules. The dissociation constant of the complex amounts to no less than 1,3 x 10−15 M. An important advantage is the fact that this complex has high thermostability and is resistant against extreme pH, denaturing agents and enzymatic degradation [3]. The fact that this technology has never been patented also plays an important role in the widespread use of this technology.
Various α-Thalassemia Genotype Combinations of the Saudi-Type Polyadenylation Signal Mutation (αT-Saudiα) in the Population of Bahrain: An Update of Genotype-Phenotype Analyses
Published in Hemoglobin, 2018
Nabeel J. Al Moamen, Ahmed Thabet, Fawzia Mahdi, Hema Newton, Ebtihal Salman
The most prominent α-thal clinical phenotype presentation discovered in Bahrain was due to the homozygosity of the Saudi-type polyA signal mutation (αT-Saudiα/αT-Saudiα), and this applies largely to other neighboring countries, especially with the rarity of α0-thal alleles in this region [18,19]. These patients presented with typical and prototypic features of Hb H disease with persistent anemic display (mean Hb level of 8.5 ± 0.7 g/dL). On the other hand, this genotype is the only one among others involving this mutation that presents consistently with intense Hb H inclusion bodies (β-globin chain homotetramer, β4) on RBCs when incubated with the cresyl blue stain. This is further evidence of the severe deficiency of α-globin chain production in this genotype with subsequent accumulation of their counterpart β-globin chains and formation of the Hb H β homotetramer. Indeed, such a severe presentation was puzzling at the initial analysis and description of this mutation [8,9]. The typical and prototypic presentation of Hb H disease is classically attributed to a deletion of three α-globin genes out of four [essentially a coinherited α0-thal allele, in which two α genes are deleted in tandem, along with an α+-thal allele, in which a single α gene is deleted; i.e. the – –/–α genotype [15,20]. However, this observation of unique ultra-severity of the αT-Saudiα mutation was attributed largely to a proposed transcriptional interference mechanism in which the mutated upstream α2-globin gene carrying the T-Saudi mutation will negatively affect transcription of the downstream α1-globin gene [10,11]. Indeed, such interference was found, in an experimental model, to lower the linked α1-globin gene expression by a staggering 5 to 20-fold level [11].