Proteoglycans of the Intervertebral Disc
Peter Ghosh in The Biology of the Intervertebral Disc, 2019
The major types of linkages found in mammalian glycoproteins are: Asn-GlcNAc (N-acetylgluctosamylasparagine): this link (referred to as an N-link as it involves the amide nitrogen of asparagine) is most commonly found in globular glycoproteins, including the hyaluronate binding site of cartilage proteoglycans. Oligosaccharides bearing this linkage usually have the same starting sugar sequence (Asn-GlcNAc-GlcNAc-Man), with subsequent branching into “antennae” after the first mannose. The first oligosaccharide sugar sequence is attached via a dolichol lipid intermediate in its biosynthesis, a process that is inhibited by the drug tunicamycin.19Ser (Thr)-GalNAc (iV-acetylgalactosamylserine): this type of link “(O-link)” is characteristic of mucins secreted by epithelial cells. It is also found in globular glycoproteins such as thyroglobin and on the protein core of cartilage proteoglycans in the attachment of keratan sulfate and O-linked oligosaccharides.Ser(Thr)-Xyl-Gal-Gal (xylosylserine): this is the linkage that attaches and chondroitin sulfates to their core proteins.Hyl-Gal and Hyl-Gal-Glc (galactosylhydroxylysine): this appears to be restricted to the triple helical domains of collagens.
Environmental toxicants on Leydig cell function
C. Yan Cheng in Spermatogenesis, 2018
No clear mutation of human SRD5A1 has been found to be associated with human diseases. The human SRD5A2 mutation is associated with male pseudohermaphroditism.46 Human SRD5A3 encodes a protein that not only catalyzes testosterone into dihydrotestosterone but also converts polyprenol to dolichol.41 The human SRD5A3 mutation causes a congenital glycosylation disorder but does not affect reproduction.44
α-Mannosidosis (β-Mannosidosis)
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Affected patients, and those with aspartylglucosaminuria, have been reported to have elevated levels of dolichol in the serum [55, 56]. This could prove useful in diagnosis. It may reflect the fact that complex glycoproteins are synthesized by the transfer of oligosaccharide precursor from dolichol to the asparagine of the peptide.
Low-glycosylated forms of both FSH and LH play major roles in the natural ovarian stimulation
Published in Upsala Journal of Medical Sciences, 2018
How is the pituitary production of low- versus fully glycosylated gonadotrophins regulated? The N-glycosylation occurs in the rough endoplasmic reticulum (ER) [see schematic drawing in Figure 7 with nomenclature, pathways, and design from refs. (22–25)]. Dolichol is a special lipid that works as a carrier of the oligosaccharide precursor. The assembly of the dolichol oligosaccharide precursor is formed on the cytoplasmic side of the ER membrane. A flippase then flips the dolichol oligosaccharide precursor across the membrane bilayer to the lumen side of the ER, where enzymes complete the oligosaccharide structure. A protein complex in the ER membrane, termed oligosaccharyltransferase (OST), transfers the oligosaccharide precursor to a gamma amino group of asparagine (-Asn-X-Thr/Ser) on nascently translated proteins.
Long-term changes of salivary exoglycosidases and their applicability as chronic alcohol-drinking and dependence markers
Published in The World Journal of Biological Psychiatry, 2019
Napoleon Waszkiewicz, Ewa Maria Kratz, Sylwia Chojnowska, Anna Zalewska, Krzysztof Zwierz, Agata Szulc, Sławomir Dariusz Szajda, Anastasiya Nestsiarovich, Andrei Kapitau, Alina Kępka, Lucyna Ostrowska, Mirosława Ferens-Sieczkowska
Impairments in the glycoconjugate metabolic processes lead to the formation of hyposialylated or high-galactose and -mannose glycoproteins and, subsequently, to the increased values of alcohol-dependence/abuse markers in various tissues, e.g. carbohydrate-deficient transferrin, sialic acid and its index of apolipoprotein J (plasma SIJ), cholesteryl ester transfer protein, HEX, dolichol, ethyl glucuronide, FAEEs, etc. (Waszkiewicz et al. 2011a, 2012a; Kratz et al. 2014). Generally, the balance between the action of salivary glycosyltransferases and glycohydrolases (between glycoconjugate synthesis and degradation) in alcohol dependence is shifted toward inhibited glycosylation and accelerated degradation processes in the saliva (Waszkiewicz et al. 2012a, 2014b). Withdrawal usually begins from 6 to 24 h after the last drink and can last for up to 1 week (McKeon et al. 2008). It was found that in some glycoproteins the tendency to correct the glycosylation profile was observed after 7 weeks of abstinence (Kratz et al. 2014). In our present study, we show for the first time that chronic alcohol drinking results in long-term deregulation of glycohydrolase activity, suggesting accelerated degradation processes of glycoconjugates in the mouth until the 50th day. The increase of exoglycosidases might also be due to the remodelling of tissues damaged by alcohol drinking (and smoking) (Chojnowska et al. 2011; Waszkiewicz et al. 2012a). This damage might mostly be due to the inflammatory effect, as the highest increase was noted for GLU and HEX A, which are described in the literature as markers of an inflammatory state (Waszkiewicz et al. 2013c); however, their increase reported so far was not as high as in alcohol-dependent persons in the current study.
Ocular Manifestations of Neuronal Ceroid Lipofuscinoses
Published in Seminars in Ophthalmology, 2021
Rohan Bir Singh, Prakash Gupta, Akash Kartik, Naba Farooqui, Sachi Singhal, Sukhman Shergill, Kanwar Partap Singh, Aniruddha Agarwal
CLN-3 is the most common neurodegenerative illness of childhood, as well as the most common type of NCL in the United States and European countries.62,63 CLN3 is characterized by an early degeneration predominant of the first and second neuron compared to other macular and generalized retinal dystrophies.64 CLN-3 gene is present on the short arm of chromosome 16, and 67 mutations have been identified associated with the CLN-3 gene.2 The inheritance of mutations occurs in an autosomal recessive manner. The most commonly reported variation is a deletion of approximately 1kb, which creates a protein product with partial function and is responsible for the classic phenotype of the illness in the presence of homozygosity.65,66 The compound heterozygosity in approximately one-fifth of the patients may account for variations in disease phenotype.67 In the remaining cases, lesser-known phenotypes of CLN-3 mutations include isolated retinitis pigmentosa without other systemic features, and autophagic vacuolar myopathy which is associated with cardiac failure.67–69Interestingly, the neurological functions are preserved in these variants. The normal protein product, Battenin, a transmembrane protein present in lysosomes and endosomes, is believed to play essential roles in endocytic trafficking, lysosomal pH regulation, cell migration and morphology, regulation of cell cycle and apoptosis.70 However, there is insufficient evidence of the role of defective protein in the pathogenesis of the disease. The current evidence suggests that lipid peroxidation, abnormal dolichol metabolism, and impaired regulation of inflammation are central to the disease pathophysiology. Accumulation of subunit c of mitochondrial ATP synthase leads to progressive neuronal apoptosis and finally leads to premature death.66
Related Knowledge Centers
- Alcohol
- Glucose
- Isoprene
- Mannose
- Oligosaccharide
- Organic Compound
- Phosphate
- Saturated & Unsaturated Compounds
- N-Linked Glycosylation
- N-Acetylglucosamine