Urolithiasis
Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed in MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
Cystinuria like most inborn errors of metabolism is inherited in an autosomal recessive pattern with the gene defect located on Chromosome 2. It has been classified into three types (I, II and III) according to the specific gene mutation although this differentiation is of little clinical relevance. The incidence of heterozygous cystinuria is about 1 in 20,000 and these individuals are at high risk of recurrent cystine urolithiasis. Patients with cystinuria have defective absorption in the jejunum of cystine, and the other dibasic amino acids ornithine, lysine and arginine. The reabsorption of these amino acids in the proximal convoluted tubule of the kidney is also abnormal leading to high levels in the urine. Cystine, in contrast to ornithine, lysine and arginine, is relatively insoluble at physiological urine pH and has a pKa of 8.3. At pH < 7.0 the solubility of cystine is approximately 250 mg/L but at pH > 7.5 its solubility increases considerably to more than 500 mg/L [12]. Patients with heterozygous cystinuria excrete <200 mg/day and usually do not form stones whereas cystine excretion in homozygous cystinurics is typically 600–1400 mg/day.
The Modification of Cystine — Cleavage of Disulfide Bonds
Roger L. Lundblad in Chemical Reagents for Protein Modification, 2020
There are several approaches to the cleavage of disulfide bonds in proteins. The majority of studies involve the cleavage of the disulfide bond of cystine to the free thiol group of cysteine by reduction. Reduction has been generally accomplished with a mild reducing agent such as β-mercaptoethanol or cysteine. Gorin and co-workers1 have examined the rate of reaction of lysozyme with various thiols. At pH 10.0 (0.025 M borate), the relative rates of reaction were β-mercaptoethanol (2-mercaptoethanol), 0.2; dithiothreitol, 1.0; 3-mercaptopropionate, 0.4; and 2-aminoethanol, 0.01. The results with aminoethanethiol were somewhat surprising since the reaction (disulfide exchange) involves the thiolate anion and 2-aminoethanethiol would be more extensively ionized than the other mercaptans. Dithiothreitol has been a useful reagent in the reduction of disulfide bonds in proteins2 as introduced by Cleland. Dithiothreitol and the isomeric form, dithioerythritol, are each capable of the quantitative reduction of disulfide bonds in proteins. Furthermore, the oxidized form of dithiothreitol has an absorbance maximum at 283 nm (Δϵ = 273) which can be used to determine the extent of disulfide bond cleavage.2 The UV spectra of dithiothreitol and oxidized dithiothreitol are shown in Figure 1. Insolubilized dihydrolipoic acid has also been proposed for use in the quantitative reduction of disulfide bonds.4
Parathyroid Hormone (Pth)
Fuad S. Ashkar, Lelio G. Colombetti in Radiobioassays, 2019
Cystine stones occur in patients with cystinuria. Uric acid and urate stones result from increased urinary uric acid concentration as in gout or in patients with abnormally acid urine. Apatite stones (phosphates of calcium) usually form in patients suffering from such disorders as hyperparathyroidism, renal tubular acidosis, Cushing’s syndrome, and other conditions associated with hypercalciuria. Oxalate stones, pure or in combination with apatite, may be found in patients with the same underlying conditions enumerated for apatite stones. Occasionally, they may be associated with primary hyperoxaluria, a congenital disease of metabolism. However, oxalate stones frequently occur in patients who are recurrent renal stone formers with no known underlying pathology. Magnesium ammonium phosphate stone formers are almost always found to have urinary tract infections.
Increased plasma glutamate in non-smokers with vasospastic angina pectoris is associated with plasma cystine and antioxidant capacity
Published in Scandinavian Cardiovascular Journal, 2022
Minako Oda, Kousuke Fujibayashi, Minoru Wakasa, Shintaro Takano, Wataru Fujita, Michihiko Kitayama, Hiroaki Nakanishi, Kazuyuki Saito, Yasuyuki Kawai, Kouji Kajinami
In addition to oxidative stress, decreased antioxidant capacity may be responsible for endothelial dysfunction. Glutathione is an important antioxidant that attenuates coronary vasospasm in patients with vasospastic angina pectoris (VSAP) [11] and reverses endothelial dysfunction in patients with atherosclerosis [12]. The synthesis of glutathione depends on the availability of the amino acid precursors, glutamate, glycine and cysteine [13]. Cystine is an oxidative form comprising two cysteines that are taken up by a specific cystine/glutamate antiporter system (XC–) in association with glutamate export. Extracellular glutamate competitively inhibits cystine import into endothelial cells [14–16]. Therefore, extracellular glutamate and cystine concentrations are crucial for glutathione biosynthesis.
Safety profile of D-penicillamine: a comprehensive pharmacovigilance analysis by FDA adverse event reporting system
Published in Expert Opinion on Drug Safety, 2021
Vijay Kumar, Anand Prakash Singh, Nicholas Wheeler, Cristi L. Galindo, Jong-Joo Kim
D-pen is also used to treat cystinuria, an inherited autosomal recessive disease caused by mutations in SLC3A1 and SLC7A9 genes. These mutations manifest high concentrations of the amino acid cystine in the urine, which enhances the formation of cystine stones in the kidneys, ureter, and bladder [20,21]. Cystinuria patients cannot properly reabsorb cystine into their bloodstream, leading to the accumulation of cystine in their urine. The excess cystine forms crystals and becomes stones that can create blockages in the urinary tract and provide sites for bacterial infections [20,21]. D-pen is used to reduce urine levels of cystine. D-pen combines and forms disulfide bonds with cysteine, resulting in the formation of a D-pen-cysteine disulfide compound that is more soluble than cystine and thereby facilitates the excretion in urine [22,23].
Novel plasma metabolite markers of attention-deficit/hyperactivity disorder identified using high-performance chemical isotope labelling-based liquid chromatography-mass spectrometry
Published in The World Journal of Biological Psychiatry, 2021
Liang-Jen Wang, Wen-Jiun Chou, Ching-Shu Tsai, Min-Jing Lee, Sheng-Yu Lee, Chia-Wei Hsu, Pei-Chun Hsueh, Chih-Ching Wu
5-hydroxylysine is a hydroxylated derivative of the amino acid lysine that is present in certain collagens. Patients with glutaric aciduria type 1, an inborn error of hydroxylysine, have been found to exhibit neuroaxonal damage, demyelination, and astrocytosis in the right frontal white matter and right lentiform nuclei (Kurul et al. 2004; Radha Rama Devi et al. 2016). L-cystine is the L-enantiomer of the sulfur-containing amino acid cystine. Glutamate exported by system x(c) is largely responsible for the extracellular glutamate concentration in the brain, while imported cystine is required to synthesise the major endogenous antioxidant. L-cystine may serve as a neuroprotective protein and signalling pathway (Albrecht et al. 2010). The results of this study showed that L-cystine was strongly and positively correlated with ADHD symptoms, which suggests that patients suffering from more severe ADHD symptoms may need more L-cystine to compensate for neurodevelopment.
Related Knowledge Centers
- Cysteine
- Disulfide
- Protein
- Protein Tertiary Structure
- Amino Acid
- Chemical Formula
- Redox
- Meso Compound
- Horn
- Empirical Formula