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Seaweed Fucoidans and Their Marine Invertebrate Animal Counterparts
Published in Se-Kwon Kim, Marine Biochemistry, 2023
Mauro Sérgio Gonçalves Pavão, Fernanda de Souza Cardoso
An additional level of complexity of sulfated glycans is found in other echinoderms. A non-linear type of chondroitin sulfate glycosaminoglycan, containing sulfated fucose branches occurs in the holothurian Ludwigothurea grisea (Figure 8.1) (Lubor Borsig et al. 2007). This glycan is isolated in significant amounts from the body wall of the sea cucumber. It is composed of a backbone similar to that of mammalian chondroitin sulfate: [4-β-D-GlcA-1→3-β-D-GalNAc-1]n, but substituted at the 3-position of the β-D-glucuronic acid residues with sulfated α-L-fucopyranosyl branches (Vieira et al. 1991). Fucose 4-O-monosulfate residues abound in the glycan chain, but 2,4- and 3,4-di-O-sulfated residues are also present. The sulfated α-L-fucose residues are concentrated toward the non-reducing end of the polysaccharide chains.
Paediatric clinical pharmacology
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Many medicines undergo glucuronide conjugation after oxidation. Other medicines undergo direct conjugation with glucuronic acid as a primary metabolic pathway. An important group of phase 2 metabolising enzymes are the UDP-glucuronyltransferases (UGTs); to date, at least 10 different UGTs have been identified. Several drugs are glucuronidated, e.g. morphine, paracetamol, codeine, lorazepam, naloxone, propofol and chloramphenicol [38]. As these drugs are metabolised by one or more different UGT isoforms, and some can also be sulphated, the effect of ontogeny on the pharmacokinetics of these drugs is not uniform.
Renal Drug-Metabolizing Enzymes in Experimental Animals and Humans
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Conjugation of xenobiotic or endogenous compounds with glucuronic acid requires the microsomal enzyme UDP-glucuronosyltransferase (UDPGT). The aglycones that serve as substrates for UDPGT include hydroxyl (phenolic and alcoholic), carboxyl, sulfhydryl, and amino compounds and the glucuronic acid moiety is derived from UDP-glucuronic acid (UDPGA). Bilirubin, thyroxine, and steroid hormones are important endogenous substrates for UDPGT (Anders, 1980). Generally, glucuronide conjugation represents a detoxification pathway leading to more rapid elimination. However, certain glucuronides of yV-hydroxy compounds such as N-hydroxy-2-acetylaminofluorene and N-hydroxy-phenacetin are more reactive than the parent compound.
Absorption, metabolism, and excretion of [14C]YY-20394, a highly selective PI3K-Delta inhibitor in humans
Published in Xenobiotica, 2022
Jinghua Yu, Hua Zhang, Yifan Zhang, Yan Zhan, Sheng Ma, Tao Hu, Ning Zhang, Yangtong Lou, Hanying Bao, Zusheng Xu, Dafang Zhong, Liyan Miao, Xingxing Diao
Glucuronic acid conjugation can transform the compound into a hydrophilic material and reduce the activity of the parent, facilitating the elimination of the drug from the body. Glucuronides are usually excreted in the urine or faeces. In our study, the glucuronic acid conjugate M764-3 was present in plasma, urine, and faeces, suggesting that M764-3 enters the systemic circulation after being transformed in the liver. Interestingly, the glucuronic acid conjugates M764-1 and M764-2 were detected only in faeces. Although this phenomenon is not common, it can be explained based on the distribution of UGT-glucuronosyltransferases. UGT-glucuronosyltransferases are widely distributed in the human liver, kidney, and gastrointestinal tract (McGurk et al. 1998; Strassburg et al. 1999, 2000). We hypothesise that M764-1 and M764-2 may be produced in the liver and then excreted in the faeces through bile. Although the β-glucuronidase of intestinal flora may hydrolyse glucuronides (Hazenberg et al. 1988; Kim and Jin 2001), the UGT-glucuronosyltransferases in the colon can regenerate glucuronic acid conjugates. Another explanation is that the parent is catalysed by UGT-glucuronosyltransferases in the colon to produce M764. However, we suggest that further studies should be performed to elucidate the mechanisms of M764 formation.
A prospective, multi-centre, follow-up clinical study evaluating the safety and effectiveness of a 24mg/ml sodium hyaluronate soft tissue filler
Published in Journal of Cosmetic and Laser Therapy, 2021
Muna Kebede, Ernst Magnus Noah, Michael Weidmann, Soo Whan Choi, Maja A. Hofmann
The material used in this study is a soft tissue filler containing 24 mg/ml of hyaluronic acid (HA). Hyaluronic acid is a naturally occurring non-sulfated glycosaminoglycan of repeating disaccharide units (d-glucuronic acid and N-acetyl-d-glucosamine) linked by β-1–3 and β-1–4 glycosidic bonds. It is a compound found ubiquitously in all living organisms. As part of the human body, it is found most abundantly in the skin, synovial fluid, the vitreous body, and the umbilical cord. The raw material for the soft filler, the salt form of hyaluronic acid (Sodium hyaluronate), is obtained from a natural and non-genetically modified bacterial stem (OGM). This highly purified and biocompatible HA is of high molecular weight and is cross-linked with BDDE (< 1ppm residual level of unreacted BDDE in the device) to slow down its degradation. The modified HA is dissolved in phosphate-buffered physiological saline and presented as an injectable hydrogel containing 24 mg/ml HA. Through hydration of the HA molecules, the gel obtains its distinct characteristics of a soft filler, maintaining liquidity and elasticity despite the high molecular weight and high HA content.
N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models
Published in Pharmaceutical Biology, 2019
Lanzhou Li, Di Wang, Xueju Wang, Ruifeng Bai, Chunyu Wang, Yin Gao, Tassos Anastassiades
Hyaluronic acid (HA) is a linear polysaccharide composed of simple repeating disaccharide units of N-acetyl-d-glucosamine (GlcNAc) and d-glucuronic acid (GlcA) (Figure 1) is the main component of the extracellular matrix and is a key component of articular cartilage and is abundant in the synovial fluid (Dahl et al. 1985). The intra-articular injection of high molecular weight HA (HMW HA) has shown moderate improvement in pain in models of arthritis including gout (Marcotti et al. 2018). HMW HA and its cross-linked preparations have been used clinically in equine and human osteoarthritis of weight-bearing joints (Bannuru et al. 2014). HA is also an important component of the renal interstitial tissue, where it is considered to regulate kidney function during normal and pathological conditions (Stridh et al. 2012).