PMM2-CDG (Congenital disorders of glycosylation, type Ia)
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Glycosylation comprises all processes in which carbohydrates are added to proteins and lipids, thereby modifying their properties. It involves a huge variety of enzymes involved in the synthesis and processing of nucleotide-activated sugars, vesicular transport and glycosylation of biomolecules directing a tremendous heterogeneity of physiologic functions. Following PMM2-CDG, related disorders of glycosylation have been discovered. By now, more than 60 entities comprise a still growing group of monogenetic diseases of glycoprotein biosynthesis termed congenital disorders of glycosylation (CDG). The oligosaccharide moieties determine critical biologic processes like protein quality control, directed protein transport, enzymatic activity, and protein stability. Deficiencies lead to multiorgan diseases with neurologic symptoms often dominating. The identification of a considerable number of “new” CDG-types afforded the improvement of nomenclature which now connects the abbreviation of defective proteins with the term CDG (e.g. deficiency of the enzyme phosphomannomutase 2 (PMM2), formerly known as CDG-Ia, changed to PMM2-CDG.
Plant Lectins in Cancer Treatment: The Case of Viscum album L.
Spyridon E. Kintzios, Maria G. Barberaki, Evangelia A. Flampouri in Plants That Fight Cancer, 2019
Lectins display great potential in cancer therapy and diagnosis by being molecules able to specifically recognize carbohydrates on the cellular membrane and their glycosylation resulting from malignancy (Mody et al. 1995). Cancer is a complex process in which genetic alterations affect and modify cell signaling, functioning, replication rhythm, apoptosis, and metastasis. Cancer cells exhibit irregular glycosylation patterns, and this process plays a significant role in cell development, signaling, interaction, proliferation, differentiation, and migration (Estrada-Martínez et al. 2017). During malignant transformation, the glycans express alterations such as over expression of certain structures, loss of expression, the appearance of novel or incomplete structures, and the accumulation of precursors (Varki et al. 2017). Glycan is a term used for any sugar or assembly of sugars, existing in a free form or attached to molecules. Glycans are involved in basic molecular and biological processes occurring in cancer affecting cell signaling, cell–cell and cell–matrix interactions, tumor cell invasion, angiogenesis, immune modulation, and metastasis (Pinho and Reis 2015). The glycosylation of proteins is the key element for a wide variety of biological processes affecting their localization, stability, and folding. Consequently, aberrant glycosylation in malignant cells results in many biological pathways affecting cell signaling, migration, adhesion, and cell death, regulating apoptosis, and autophagy (Korekane and Taniguchi 2015).
Receptors and Signal Transduction Pathways Involved in Autonomic Responses
Kenneth J. Broadley in Autonomic Pharmacology, 2017
Single cysteine residues that are thought to form disulphide bonds to stabilize the receptor structure are conserved among most of the receptors in the first two extracellular loops (Figure 13.1 and 13.2). The extracellular amino terminals vary considerably in length, from as few as seven amino acids in the adenosine A2 receptor to 68 in the human cloned m3 receptor. The amino terminal chain usually contains asparagine groups for N-glycosylation in a sequence, Asn-X-Ser/Thr. α2-, β1 and β2-Adrenoceptors have several glycosylation sites, but they are absent in α2B and adenosine receptors. Glycosylation involves the addition of a carbohydrate chain, which is always on the outside of the cell membrane and linked to a serine, threonine or asparagine amino acid, usually through N-acetylglucosamine or N-acetylgalactosamine.
Tissue N-linked glycosylation as potential prognostic biomarker for biochemical recurrence-free survival
Published in Biomarkers, 2021
Tijl Vermassen, Arne Van Den Broeck, Nicolaas Lumen, Nico Callewaert, Sylvie Rottey, Joris Delanghe
Glycomics could therefore be an asset. Glycosylation is a post-translational modification forming complex cell surface and extracellular matrix glycoproteins needed for cell–cell communication, cell structure maintenance and self-recognition by the immune system (Paradis 2005). Glycosylation is strongly biochemically influenced and can be altered in cancer. Most noted aberrations in the N-glycan profile were found for sialylation, fucosylation and branching of complex N-glycan structures, which could possibly be used as novel diagnostic and prognostic biomarkers in PCa (Scott et al. 2019). This was described in previously research from our group in which promising results were noticed for urine N-glycosylation to differentiate PCa from other prostate pathologies. Herein, it was shown that both core-fucosylation and the number of triantennary structures was decreased in patients with PCa (Vermassen et al.2012, 2014, 2015a, 2015b, 2019a).
Searching for glycomic biomarkers for predicting resilience and vulnerability in a rat model of posttraumatic stress disorder
Published in Stress, 2020
Csilla Lea Fazekas, Eszter Sipos, Thomas Klaric, Bibiána Török, Manon Bellardie, Gordana Nedic Erjave, Matea Nikolac Perkovic, Gordan Lauc, Nela Pivac, Dóra Zelena
Glycans are enzymatic post-translational modificators of proteins and lipids (Ohtsubo & Marth, 2006). N-linked glycosylation is the most common type (Pivac et al., 2011) and it can modulate the function of a protein to be able to adapt to the constantly changing environment (Lauc et al., 2016). Dysregulation of glycosylation is associated with a wide range of diseases, including cancer, diabetes, cardiovascular and immunological disorders (Ohtsubo & Marth, 2006). About 80% of the glycosylation-related disorders affect the nervous system, providing a plausible and comprehensive explanation for the diverse pathomechanisms. It might be explained by the existence of the perineuronal net composed of glycans, serving as a regulatory factor for interneuronal communication (Wen et al., 2018). Recent technological advances allow reliable, high-throughput quantification of glycans (Pivac et al., 2011). In relation to psychiatric disorders, changes in glycan-related processes were found in attention deficit hyperactivity disorder (ADHD) (Pivac et al., 2011), Alzheimer’s disease, Parkinson’s disease (Shi et al., 2013), autism and schizophrenia (Barone et al., 2012). However, glycan alterations in relation to PTSD were not extensively studied so far. A small case report failed to find alteration (Moreno-Villanueva et al., 2013), while our recent human study on 543 male war veterans found 6 plasma N-glycans to be associated with PTSD (Tudor et al., 2019). There is no information on glycosylation patterns in animal models of PTSD, however, there are few studies on stressed animals (Konjevod et al., 2019).
Mass spectrometry for the identification and analysis of highly complex glycosylation of therapeutic or pathogenic proteins
Published in Expert Review of Proteomics, 2020
Yukako Ohyama, Kazuki Nakajima, Matthew B. Renfrow, Jan Novak, Kazuo Takahashi
The expression patterns of some glycosyltransferases and glycosidases, the enzymes that compose the glycosylation pathways, are often altered in pathological conditions, such as cancer and autoimmune diseases [45–48]. Identification of the specific glycoforms in a disease and clarifying their relationship with clinical prognosis could potentially lead to the development of new biomarkers with diagnostic and prognostic significance. Furthermore, detecting the antigenic glycoforms that cause disease informs development of novel therapeutic drugs and vaccines, e.g., MUC1-peptide vaccines for cancer [127]. The glycosylation patterns of therapeutic proteins are important for their pharmacokinetic properties, biological functions, and safety. The glycoengineering of therapeutic proteins is becoming important for improving their therapeutic effect. Furthermore, in the near future, many biosimilars will be developed, and their structure (including primary structures, high-order structures, and PTMs), function, and safety have to be monitored through the development process. The detailed analysis of glycosylation in the reference product and comparison with glycosylation in newly developed biosimilar should be reported. Furthermore, lot-to-lot variability assessment of products may also be required.
Related Knowledge Centers
- Cytoplasm
- Glycan
- Glycation
- Carbohydrate
- Glycosyl Donor
- Glycosyl Acceptor
- Glycoconjugate
- Post-Translational Modification
- Endoplasmic Reticulum
- O-Glcnac