Medium-chain acyl CoA dehydrogenase deficiency
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Medium-chain dicarboxylic aciduria is the hallmark of the organic acid profile in the urine of the patient with this disease, and it may be diagnostic at the time of the acute episode [15]. The typical pattern is that of large amounts of the dicarboxylic acids, adipic (C6), suberic (C8), and sebacic (C10), as well as the glycine conjugates of hexanoic acid and suberic acid. The very large elevation of suberylglycine may be diagnostic [26, 27]. Dicarboxylic acids as long as C12 (dodecanedoic) acid maybe elevated, and omega-1 oxidation yields the hydroxy acids, 5-hydroxy-hexanoic and 7-hydroxy-octanoic acids [28]. Normal infants and children excrete large amounts of dicarboxylic acids with fasting, but the attendant ketosis is mirrored in very large excretions of 3-hydroxybutyric acid and acetoacetic acid. In contrast, in patients with disorders of fatty acid oxidation, the ratio of dicarboxylic acids to the sum of these two compounds is greater than 1 [2]. Unfortunately, these diagnostic features disappear from the urine with the disappearance of the acute episode, so that by the time the patient is referred for study, the organic acid analysis of the urine is usually completely normal.
Physical Chemistry of Bilirubin: Binding to Macromolecules and Membranes
Karel P. M. Heirwegh, Stanley B. Brown in Bilirubin, 1982
Accurate determination of pK-values of bilirubin cannot be based on determinations in aqueous media, due to insolubility of the acid and instability of the tetraanion. Electrometric titration in DMSO15 gives normally shaped curves and indicates that the two carboxyl groups have nearly identical pK’s, and likewise the two lactams. This result at first seemed surprising since it was expected that the mono-anion would dissociate less readily than the uncharged acid and the trianion less readily than the dianion. On the other hand, the two carboxyl groups may be located with a fairly long distance between them, approximately as in an aliphatic dicarboxylic acid with eleven carbon atoms which, in fact, has nearly identical pK values of the two protons. Also the lactams are situated far apart in the molecule.
Transport and Metabolism of Glutamine and Glutamate in the Small Intestine
Elling Kvamme in Glutamine and Glutamate in Mammals, 1988
Thus by the late 1950s it was well established for several species that glutamate and aspartate were absorbed from the lumen of the small intestine and some of the amino-N was secreted from the serosal face of the epithelium as alanine. But how complete was this transamination? Parsons and Volman-Mitchell13 attempted to answer this question by studying absorption and transamination of glutamate and aspartate in vitro from reasonably physiological concentrations in the lumen. Concentrations of free dicarboxylic acids of up to 7 mM have been reported in the human intestine and in these in vitro experiments concentrations of 10 mM were used. It was found that in the rat, alanine contributed up to 85% of the amino-N secreted at the serosal surface while from the guinea pig and chicken, the proportion was not more than 60%. In the rat and guinea pig the contribution of alanine to the aminoN secreted was similar in jejunum and ileum. For the different species the extent of transamination during absorption was related to the total activity of alanine aminotransferase in the tissue. There was evidently a limit to the capacity of the intestinal mucosa to subject the dicarboxylic amino acids to transamination during absorption but it seems unlikely that this limit will be reached in vivo.
Variable sensitivity to diethylene glycol poisoning is related to differences in the uptake transporter for the toxic metabolite diglycolic acid
Published in Clinical Toxicology, 2023
Julie D. Tobin, Courtney N. Jamison, Corie N. Robinson, Kenneth E. McMartin
Diglycolic acid is a 4-carbon dicarboxylic acid, similar in structure to the citric acid cycle intermediate, succinate. Succinate is taken into kidney cells by the SLC13 family of solute carriers known as the sodium dicarboxylate transporters (NaDC-1 and NaDC-3) [18]. Sodium-dependent dicarboxylate transporter-1 has broad substrate specificity, with preference for four carbon dicarboxylates, such as succinate and possibly DGA. Previous studies using human proximal tubule (HPT) cells in culture have shown that treatment with a small molecule inhibitor of NaDC-1 markedly reduced the uptakes of both succinate and DGA [11]. Also, the uptake of succinate and the toxicity of DGA were reduced in cells pre-treated with siRNA to knockdown NaDC-1 function. Lastly, DGA reduced the uptake of succinate by these cells. Parallel studies examining the role of NaDC-3 were not definitive for a role of NaDC-3 in DGA uptake. Taken together, these studies indicate that DGA is likely taken into kidney cells by the NaDC-1 transporter. Hence for this study, we have specifically focused on differences in NaDC-1 transporter expression.
Comparison of the relative stability of pharmaceutical cocrystals consisting of paracetamol and dicarboxylic acids
Published in Drug Development and Industrial Pharmacy, 2018
Naoto Suzuki, Masatoshi Kawahata, Kentaro Yamaguchi, Toyofumi Suzuki, Kazuo Tomono, Toshiro Fukami
Furthermore, the intermolecular interactions between APAP and dicarboxylic acid were evaluated using the method reported by Aakeröy et al. [14] to judge whether these complexes were cocrystals or salts, where the distance between the C–O atoms in the carboxyl groups of each cocrystal was measured, and the ratios were also calculated. The ratios of APAP–OXA were 1.030 and 1.041, and those of APAP–MLA were 1.056 and 1.080 (Figure 3(A,B)). In the case of proton transfer, the average charge between the C–O moieties resulted in nearly equal atomic distances, i.e. the ratio of both distances was approximately one. Comparing APAP–MLA with APAP–OXA was difficult because APAP–MLA contained intramolecular hydrogen bonds. In addition, the hydrogen bond network in APAP–MLA existed between –OH and –C = O moieties, –OH and –OH moieties, –C = O moieties and –NH moieties of amide groups. Therefore, proton transfer was unlikely in this combination. Thus, every molecular interaction of APAP–MLA involved a hydrogen bond without proton transfer, and APAP–MLA was classified as a cocrystal. These results show that the cocrystals consisting of APAP and dicarboxylic acids had stoichiometric ratios of 1:1.
Biomimetic hydroxyapatite/poly xylitol sebacic adibate/vitamin K nanocomposite for enhancing bone regeneration
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Zhipeng Dai, Minyan Dang, Wenzhi Zhang, Sumathra Murugan, Seoh Wei Teh, Haiyan Pan
Ecological polymers comprise of a well-liked group of biomaterials that are extensively deliberated for use in various resorbable sutures, implants and other features like tissue scaffolds, breakage fascination devices and drug/gene delivery [20]. Few studies have presented that a topographic substrate is able to mimic an in vivo microenvironment self-possessed of channels, pores, and ridges to support physically prompted cells at a nanoscale level [21,22]. Polyesters are generally favoured among eco-friendly polymers for both drug delivery and rejuvenative drugs due to their countless compensation, in exacting, their hydrolytic cleavage in the hydrophilic environment in vivo [23–25]. The dicarboxylic acids worn in this exertion were sebacic acid, adipic acids that have been exposed to be cytocompatible [26,27].
Related Knowledge Centers
- Adipic Acid
- Aromatic Compound
- Carboxylic Acid
- Copolymer
- Organic Chemistry
- Organic Compound
- Polyamide
- Polyester
- Chemical Formula
- Aliphatic Compound