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4-Hydroxybutyric aciduria
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Among disorders of GABA metabolism 4-hydroxybutyric aciduria has been more frequently encountered, probably because the key intermediate 4-hydroxybutyric acid is detectable by analysis of organic acids [2]. The fundamental defect is in the activity of the succinic semialdehyde dehydrogenase (EC 1.2.1.24) (Figure 13.1). In the reaction catalyzed by this enzyme, the product of GABA transamination is normally converted to succinic acid and hence to oxidation via the citric acid cycle [9]. 4-Hydroxybutyric acid is converted via β-oxidation into 3,4-dihydroxybutyric acid and thereafter to its keto acid, to glycolaldehyde and glycolic acid [10].
The Modification of Lysine
Published in Roger L. Lundblad, Chemical Reagents for Protein Modification, 2020
In another study, the reversible reductive alkylation of proteins has been examined.106 Both glycolaldehyde and acetol will react with the primary amino groups in proteins to yield derivatives which can be cleaved with periodate under mild basic condition to yield the free amine. Figure 33 shows the distribution of reaction products of lysine and glycolaldehyde as a function of pH with either sodium borohydride (A) or sodium cyanoborohydride (B) as the reducing agent. It is apparent that sodium cyanoborohydride is much more effective in the range of pH 6.0 to pH 8.0 while sodium borohydride is more effective under more alkaline conditions. Treatment of 30.0 mg lysozyme in 6.0 ml 0.2 M sodium borate, pH 9.0, with 60 mg glycoladehyde and 10 mg sodium borohydride at ambient temperature resulted in 60% 2-hydroxyethylation. Treatment of 20 mg ovomucoid in 2.0 ml 0.2 M sodium borate, pH 9.0 with 10% acetol and 30 mg sodium borohydride (added in portions) resulted in 55% hydroxyisopropylation. In both situations, the reaction was terminated by adjustment of the pH to 5 with glacial acetic acid. The extent of modification was determined either by titration with trinitrobenzenesulfonic acid and/or by amino acid analysis after acid hydrolysis. Periodate oxidation could be accomplished with 0.015 M sodium periodate at pH 7.9 for 30 min at ambient temperature.
Xenobiotic Biotransformation
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
Aldehyde dehydrogenases (EC 1.2.1.3.) catalyze the oxidation of aldehydes to acids by using NAD as co-factor. The physiological substrates for the enzymes are unknown; the substrate specificity is broad. Classical substrates include acetaldehyde, formaldehyde, and glycolaldehyde, which are the biotransformation products of ethanol, methanol, and ethylene glycol, respectively. The enzymes are present in all organs and in cytosol, mitochondria and microsomes. Liver has the highest activity, but kidney also possesses high activity. The enzymes exist as several isozymes within the cytosolic, mitochrondrial, and microsomal compartments. One cytosolic isozyme is specific for the oxidation of formaldehyde complexed with glutathione and is referred to as formaldehyde dehydrogenase. Additional isozymes within the cytosol are differentiated by selective induction with PB or TCDD and 3-MC. The isozyme induced by TCDD and 3-MC has received special study due to its increased activity in tumor cells [see Marselos and Lindahl (1988)]. Since acetaldehyde is preferentially oxidized in mitochondria, an isozyme for its oxidation may be localized in these structures. Additional mitochrondrial isozymes can be differentiated by selective inhibition with the prototype aldehyde dehydrogenase inhibitor, disulfiram.
Effects of Dietary Phytochemicals on DNA Damage in Cancer Cells
Published in Nutrition and Cancer, 2023
Yang Ye, Ying Ma, Mei Kong, Zhihua Wang, Kang Sun, Fang Li
Benzyl isothiocyanate (BITC) is formed by the hydrolysis of glycolaldehyde in cruciferous vegetables such as broccoli and cabbage. BITC exerts anticancer effects by regulating various processes such as apoptosis, autophagy, cell cycle arrest, and angiogenesis (102). It induces G2/M cell cycle arrest and inhibits the proliferation of cells. In a previous study (103), glioblastoma multiforme 8401 cells were treated with BITC; two DNA damage-related genes were identified using complementary DNA chip technology: DNA-damage-inducible transcript three and GADD45A genes. Yeh et al. (23) demonstrated that BITC significantly increases expression of the DNA oxidative damage marker 8-OHDG in human oral cancer OC2 cells and activates the ATM-CHK2-p53 pathway as well as induces G2/M cell cycle arrest and apoptosis. In human pancreatic cancer cells, BITC induces H2AX phosphorylation and inhibits cell proliferation. BITC activates the CHK2 kinase associated with the DNA damage checkpoint and significantly reduces the protein expression of CDC25C, CDC-2, and cyclin B1 (24). Together, these results suggest that BITC inhibits tumor proliferation by regulating DNA damage.
Aldehyde toxicity and metabolism: the role of aldehyde dehydrogenases in detoxification, drug resistance and carcinogenesis
Published in Drug Metabolism Reviews, 2019
Amaj Ahmed Laskar, Hina Younus
Aldehydes are a large class of organic compounds having a carbonyl carbon atom substituted with at least one hydrogen atom along with additional functional moieties. Aldehyde family is generally represented by R-CHO, where R is any functional moiety/carbon-containing substituent. Based on the nature of R group, aldehydes are divided into different subclasses. Broadly, they are classified into aliphatic and aromatic aldehydes which can be either saturated or unsaturated (Feron et al. 1991; Koren and Bisesi 2003). The different subclasses of aldehydes are (i) short chain aldehydes such as formaldehyde, acetaldehyde; (ii) long chain aldehydes such as hexanal, nonanal; (iii) aromatic aldehydes such as cinnamaldehyde, benzaldehyde; (iv) α,β-unsaturated aldehydes such as citral, acrolein; and (v) α-oxoaldehydes such as glyoxal, glycolaldehyde (O’Brien et al. 2005; LoPachin and Gavin 2014).
Glyceraldehyde-derived advanced glycation end-products are associated with left ventricular ejection fraction and brain natriuretic peptide in patients with diabetic adverse cardiac remodeling
Published in Scandinavian Cardiovascular Journal, 2022
Yuushi Yasuda, Hirofumi Aoki, Wataru Fujita, Kousuke Fujibayashi, Minoru Wakasa, Yasuyuki Kawai, Hiroaki Nakanishi, Kazuyuki Saito, Masayoshi Takeuchi, Kouji Kajinami
Diabetes mellitus (DM) is a major issue health worldwide. Hyperglycemia in DM causes various cardiovascular complications leading to loss of quality of life and death [1,2]. Recent studies have shown that patients with DM have a significantly increased risk of heart failure. The main causes of heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) in patients with DM are coronary artery disease (CAD) and hypertension [3,4]. Although recent guidelines [5] reported that the existence of diabetic cardiomyopathy remained unconfirmed, other reports have shown the existence of a condition showing diabetic adverse cardiac remodeling (DbCR) without CAD and hypertension; this DbCR condition is associated with HFrEF, HFpEF, and death is clinically important [3–7]. In recent decades, extensive studies have shown that advanced glycation end-products (AGEs), formed by continuous hyperglycemia in patients with DM, cause myocardial damage leading to diabetic cardiomyopathy [8–10]. AGEs are end-products of a nonenzymatic reaction of sugar and lipid adducts with proteins (the Maillard reaction); AGEs form cross-links among the proteins of long-living tissues causing an age-related accumulation of AGEs in the body, a process that is accelerated in patients with DM [11–13]. AGEs have chemically heterogeneous structures. Among seven immunochemically distinct classes of AGEs (glucose-derived AGEs, fructose-derived AGEs, glyceraldehyde-derived AGEs, glycolaldehyde-derived AGEs, methylglyoxal-derived AGEs, glyoxal-derived AGEs, and 3-deoxyglucosone-derived AGEs) detected in the sera of patients with type 2 DM, especially those who are on hemodialysis, glyceraldehyde-derived AGEs (Glycer-AGEs) have been reported to have the strongest binding affinity for the receptor for AGEs (RAGE), subsequently eliciting oxidative generation and vascular inflammation, leading in turn to progressive atherosclerosis in patients with DM [13].