128 research outputs found
Clinical, Genetic, and Protein Structural Aspects of Familial Dysalbuminemic Hyperthyroxinemia and Hypertriiodothyroninemia
No full textFamilial dysalbuminemic hyperthyroxinemia (FDH-T4) and hypertriiodothyroninemia (FDH-T3) are dominantly inherited syndromes characterized by a high concentration of thyroid hormone in the blood stream. The syndromes do not cause disease, because the concentration of free hormone is normal, but affected individuals are at risk of erroneous treatment. FDH-T4 is the most common cause of euthyroid hyperthyroxinemia in Caucasian populations in which its prevalence is about 1 in 10,000 individuals, but the prevalence can be much higher in some ethnic groups. The condition is caused by a genetic variant of human serum albumin (HSA); Arg218 is mutated to histidine, proline, or serine or Arg222 is changed to isoleucine. The disorder is characterized by greater elevation in serum l-thyroxine (T4) than in serum triiodothyronine (T3); T4 can be increased by a factor 8–15. The high serum concentration of T4 is due to modification of a binding site located in the N-terminal half of HSA (in subdomain IIA). Thus, mutating Arg218 or Arg222 for a smaller amino acid reduces the steric restrictions in the site and creates a high-affinity binding site. The mutations can also affect binding of other ligands and can perhaps cause modified pharmacokinetics of albumin-binding drugs. In normal HSA, the high-affinity site has another location (in subdomain IIIB). Different locations of these sites imply that persons with and without FDH-T4 can have different types of interactions, and thereby complications, when given albumin-binding drugs. FDH-T3 is caused by a leucine to proline mutation in position 66 of HSA, which results in a large increment of the binding affinity for T3 but not for T4. For avoiding unwanted treatment of euthyroid persons with hyperthyroxinemia or hypertriiodothyroninemia, protein sequencing and/or sequencing of the albumin gene should be performed
Mutations and polymorphisms of the gene of the major human blood protein, serum albumin
No full textWe have tabulated the 77 currently known mutations of the familiar human blood protein, serum albumin
(ALB). A total of 65 mutations result in bisalbuminemia. Physiological and structural effects of these mutations
are included where observed. Most of the changes are benign. The majority of them were detected upon clinical
electrophoretic studies, as a result of a point mutation of a charged amino acid residue. Three were discovered
by their strong binding of thyroxine or triiodothyronine. A total of 12 of the tabulated mutations result in
analbuminemia, defined as a serum albumin concentration of <1 g/L. These were generally detected upon
finding a low albumin concentration in patients with mild edema, and involve either splicing errors negating
translation or premature stop codons producing truncated albumin molecules. A total of nine mutations, five of
those with analbuminemia and four resulting in variants modified near the C-terminal end, cause frameshifts.
Allotypes from three of the point mutations become N-glycosylated and one C-terminal frameshift mutation
shows O-glycosylation
GENETIC VARIANTS OF HUMAN SERUM ALBUMIN: MOLECULAR AND FUNCTIONAL ASPECTS AND THERAPEUTIC POSSIBILITIES
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Molecular Genetics of Analbuminemia
No full textCongenitalanalbuminaemia (CAA) is a very rare condition
manifested by the near complete absence of albumin, the
major blood protein, because of defects in the albumin
(ALB) gene. It is generally regarded as relatively benign in
adults, but analbuminaemic individuals may be at risk
during the perinatal and childhood period. Twenty-one
different molecular lesions in the ALB are now known as
cause of the trait. These include one mutation in the start
codon, one frameshift/insertion, five frameshift/deletions,
seven nonsense mutations and seven mutations
affecting splicing. Thus, nonsense mutations, mutations
affecting splicing and frameshift/deletions seem to be
the most common causes of CAA. These results indicate
that the trait is an allelic heterogeneous disorder caused
by homozygous or, in a single case, compound heterozygous
inheritance of defects. Most mutations are unique,
but one, named Kayseri, is responsible for about half of
the known cases
Mutants and molecular dockings reveal that the primary L-thyroxine binding site in human serum albumin is not the one which can cause familial dysalbuminemic hyperthyroxinemia
No full textPossible Mechanisms by Which Enzymatic Degradation of Human Serum Albumin Can Lead to Bioactive Peptides and Biomarkers
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Possible Mechanisms by Which Enzymatic Degradation of Human Serum Albumin Can Lead to Bioactive Peptides and Biomarkers
No full textPartial enzymatic degradation of human serum albumin in vivo can lead to the generation of peptides with novel functions or to peptides that might serve as biomarkers for disease. In pathological conditions, biomarkers are possibly produced from the protein in the lysosomes and set free by cell death, or cell death could release acid endoproteases which produce biomarkers by degrading extracellular albumin. Alternatively, lysosomes or secretory granules can be stimulated to release enzymes which produce bioactive peptides from albumin. In physiological conditions, it is proposed that bioactive peptides can be made by enzymatic attack on the protein bound to the endosomal neonatal Fc receptor. The peptides formed could leave the cell, together with native albumin, by exocytosis. Thus, the receptor could have a new function in addition to saving albumin from degradation in the lysosomes. Large amounts of albumin are degraded every day, and this fact can compensate for the short in vivo half-lives of the bioactive peptides. One or more of the procedures outlined above could also apply to other plasma proteins or to structural proteins
Sociological implications of scientific publishing: Open access, science, society, democracy and the digital divide
No full textClaims for open access are mostly underpinned with
1. science—related arguments (open access accelerates scientific communication);
2. financial arguments (open access relieves the serials crisis);
3. social arguments (open access reduces the digital divide);
4. democracy—related arguments (open access facilitates participation); and,
5. socio—political arguments (open access levels disparities).
Using sociological concepts and notions, this article focuses strongly on Pierre Bourdieu\u27;s theory of (scientific) capital and its implications for the acceptance of open access, Michel Foucault\u27;s discourse analysis and the implications of open access for the concept of the digital divide. Bourdieu\u27;s theory of capital implies that the acceptance of open access depends on the logic of power and the accumulation of scientific capital. It does not depend on slogans derived from hagiographic self—perceptions of science (e.g., the acceleration of scientific communication) and scientists (e.g., their will to share their information freely). According to Bourdieu\u27;s theory, it is crucial for open access (and associated concepts like alternative impact metrics) to understand how scientists perceive its potential influence on existing processes of capital accumulation and how open access will affect their demand for status. Foucault\u27;s discourse analysis suggests that open access may intensify disparities, scientocentrism and ethnocentrism. Additionally, several concepts from the philosophy of sciences (Popper, Kuhn, Feyerabend) and their implicit connection to the concept of open access are described in this paper
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