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Airway Repair and Adaptation to Inhalation Injury
Published in Jacob Loke, Pathophysiology and Treatment of Inhalation Injuries, 2020
S. F. Paul Man, William C. Hulbert
There is a continuum of epithelial injuries due to the inhalation of noxious gases and fumes that exist in our environment today; the exposure extremes vary between acute massive and chronic low level. A massive exposure is usually the result of an accident, industrial or otherwise; often there are systemic effects in addition to severe injury to the lungs and eyes, and there is significant morbidity and mortality. Two recent examples of this level of exposure were the sodium cyanate exposure in Bhopal, India, where a large population was at risk, and the Lodgepole sour gas well blow out (of which hydrogen sulfide was a major component) in Alberta, Canada, where a few individuals were injured. These incidences are significant because they were industrial accidents, are potentially preventable, and invariably occur in or near populated areas.
The Modification of Lysine
Published in Roger L. Lundblad, Chemical Reagents for Protein Modification, 2020
The reaction of primary amino groups in proteins with cyanate (Figure 10) has been a useful procedure for several decades. Stark and co-workers53 pursued the observation that ribonuclease was inactivated by urea in a time-dependent reaction. It was established that this inactivation was a reflection of the content of cyanate in the urea preparation (Figure 11). This observation was subsequently developed into a method for the quantitative determination of amino-terminal residues in peptides and proteins.54 The reaction of cyanate with amino acid residues has been reported by Stark.55 The ϵ-amino group of lysine is the least reactive (k = 2.0 × 10−3M−1 min−1) as compared to the α-amino group of glycylglycine (k = 1.4 × 10−1M−1 min−1). The carbamyl derivative of histidine is quite unstable as is the corresponding derivative of cysteine. Concern should be given to reaction at residues other than amines. For example, the reaction of chymotrypsin with cyanate results in loss of catalytic activity associated with the carbamylation of the active-site serine residue.56
Colon Carcinogenesis: Biochemical Changes
Published in Herman Autrup, Gary M. Williams, Experimental Colon Carcinogenesis, 2019
Young S. Kim, Laurence J. Mcintyre
Allfrey et al.35 investigated the effect of sodium cyanate on protein synthesis in normal rat colonic mucosa and in DMH-induced colon tumors. They found that the incorporation of tritiated amino acids into protein was suppressed to a much greater extent in the tumor tissue than in the surrounding colonic epithelium. They also found the cyanate had little or no effect on cell lines derived from human colonic adenocarcinoma. This anomaly was explained in a recent study which demonstrated that sodium cyanate requires in vivo metabolism for its effect.36 A similar sensitivity of protein synthesis to cyanate inhibition can be observed in the transplantable murine colonic tumor system.36
Potential interference of in vitro carbamylation on C-reactive protein laboratory measurement
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2023
Carolina dos Santos Stein, José Pedro Etchepare Cassol, Rafael Noal Moresco
Carbamylation is a nonenzymatic protein modification caused by the interaction of proteins with isocyanic acid, which results in conformational and functional changes [1]. This process occurs frequently in chronic kidney disease (CKD), as impaired kidney function leads to urea accumulation, and dissociation of this molecule results in the formation of cyanate ions [2]. Another source of cyanate is the enzymatic oxidation of thiocyanate, which originates from diet, smoking, or environmental conditions through the action of myeloperoxidase (MPO) [1]. Inflammatory conditions can enhance carbamylation owing to neutrophil recruitment and consequent exacerbation of MPO activity [3,4]. Notably, inflammation is observed in CKD, which results in increased cardiovascular risk and oxidative imbalance in these patients [5]. As a result of the irreversible nature of carbamylation, the consequences of this process reach the molecular level and reflect the subsequent cellular and systemic outcomes [6]. The related effects of carbamylation on some proteins include impaired clot formation by fibrinogen [7], decreased antiatherogenic effects of high-density lipoprotein [8], and increased arterial stiffness after elastin carbamylation [9].
Association of rheumatoid arthritis disease activity and antibodies to periodontal bacteria with serum lipoprotein profile in drug naive patients
Published in Annals of Medicine, 2020
Aulikki Kononoff, Pia Elfving, Pirkko Pussinen, Sohvi Hörkkö, Hannu Kautiainen, Leena Arstila, Leena Laasonen, Elina Savolainen, Helena Niinisalo, Jarno Rutanen, Olga Marjoniemi, Mari Hämäläinen, Katriina Vuolteenaho, Eeva Moilanen, Oili Kaipiainen-Seppänen
Carbamylation, a form of post-translational modification, can occur spontaneously or via a route assisted by myeloperoxidase [11]. Myeloperoxidase catalyses the oxidation of thiocyanate to cyanate. The active form of cyanate acts as a potential toxin and interacts with the amine groups of proteins generating homocitrulline [12]. Smoking elevates serum thiocyanate levels and may facilitate carbamylation by myeloperoxidase. The development of seropositive RA is associated with smoking [13]. As a proof of in vivo occurrence, immunoglobulin (Ig) G antibodies recognizing homocitrulline-containing antigens in serum, carbamylated Igs in synovial fluid and protein-bound homocitrulline in joint tissues have been described in RA (reviewed in [14]). Carbamylation also occurs in lipoprotein particles. Carbamylation of 15% of lysine residues completely abolished the interaction of LDL particle with its receptor [15]. Extensively carbamylated LDL is efficiently cleared from the circulation, whereas minimally carbamylated LDL has decreased clearance [16].
New and emerging treatments for vaso-occlusive pain in sickle cell disease
Published in Expert Review of Hematology, 2019
Intravenous urea was investigated as a molecule that might inhibit the hydrophobic interactions with other hemoglobin molecules that trigger polymerization but was ineffective at tolerable doses in an early multicenter clinical trial [145]. Similarly, the use of sodium cyanate was studied in a large clinical trial [146], as cyanate can carbamylate the amino-terminal valine of the alpha and beta-globin chains, which prevents polymerization. While a modest decrease in hemolysis was observed, long-term use was associated with the development of a cyanate-induced polyneuropathy [147], and further development was abandoned. More recently, agents that bind via Schiff bases to the alpha-globin N terminus, 5-hydroxymethyl-furfural (Aes-103) [148] and GBT440 [149], have been developed. The later agent, now identified as Voxelotor, is in phase II pediatric trials (NCT02850406) and phase III clinical trials in adolescents and adults (NCT03036813), and appears promising [150].