Neurocutaneous Syndromes With Interstitial Lung Disease
Lourdes R. Laraya-Cuasay, Walter T. Hughes in Interstitial Lung Diseases in Children, 2019
Ataxia-telangiectasia (AT) or Louis-Bar syndrome is a primary immunodeficiency transmitted on an autosomal recessive basis. The main features of this complex disease are cutaneous and bulbar telangiectases, progressive cerebellar degeneration, repeated sinopul-monary infections, endocrine abnormalities, and increased likelihood of cancer. Deficiency of immunoglobulin A and immunoglobulin E are the most common abnormalities.39,40 Variable deficiencies in cell-mediated and/or antibody-mediated immune system are present.41-44 The clinical expression and progression of the disease are variable but ultimate deterioration is inevitable. The variability is attributed to immunologic attrition which may be related to “exhaustion” of the immunologic system as a result of chronic infection or to a more basic defect. Analysis of collagen from two patients revealed deficiency of hydroxylysine suggesting a basic structural component defect.45 This study was an attempt to support defective mesenchymal embryogenesis inasmuch as AT has thymic defect, telangiectases, and gonadal abnormalities.
Molecular Structure and Functions of Collagen
Marcel E. Nimni in Collagen, 1988
Proline analogs, such as cis-hydroxyproline and azetidine 2-carboxylic acid, are known to be incorporated into collagen in the proline position and to inhibit triple helix formation within the cell. Using such an experimental tool, it was shown that the glycosylation of hydroxylysine35 and the hydroxylation of proline at the 3 position28 are increased approximately twofold by inhibiting helix formation. These observations, coupled with the time factors noted above, may be linked to the increased hydroxylation of proline in the 3 position, the increased content of hydroxylysine, and the greater degree of glycosylation seen in basement membrane collagen, and may explain differences in hydroxylation seen in pathological connective tissues.
Vitamin C (Ascorbic Acid)
Luke R. Bucci in Nutrition Applied to Injury Rehabilitation and Sports Medicine, 2020
Table 1 lists some of the more pertinent roles and functions of ascorbate for connective tissue healing.93,94,163,164,170,179,439,485,673–679 The major role of ascorbate in connective tissues is in activation of α-ketoglutarate linked, iron-containing hydroxylases (prolyl hydroxylases and lysyl hydroxylases). These enzymes are critical for proper posttranscriptional modification of collagen chains by formation of hydroxyproline and hydroxylysine residues. These modified amino acids confer shape and biological function for collagens throughout the body, which are the major component of connective tissues, and essential for repair and healing processes to occur. Ascorbate is also a direct antioxidant and can “recharge” other antioxidants, especially tocopherol. Thus, ascorbate may play protective roles during expression of free radicals in pain and inflammation. Ascorbate is a potent reducing agent or oxidizing agent, depending upon conditions, and can participate in a nonspecific manner in many enzymatic reactions. Ascorbate appears to have noncofactor effects on regulation of collagen gene transcription. This means that ascorbate is more than a simple redox compound. Most of the functions of ascorbate are directly applicable to the health of connective tissues and their responses to injury.
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.
Proteomes of the past: the pursuit of proteins in paleontology
Published in Expert Review of Proteomics, 2019
Graptolites occur in Paleozoic strata and today. They are small, worm shaped marine creatures that secrete tube-shaped organic thecae, thought to be composed of collagen or chitin. The periderm of some Ordovician graptolites exhibited collagen-like structures imaged by wide-angle X-ray diffraction in 1972 by Towe and Urbanek [107]. The researchers found a few amino acids, but not the 4-hydroxyproline or 5-hydroxylysine characteristic of collagen. The Towe and Urbanek results were thus not definitive for original collagen, but were consistent with altered collagenous or chitinous residues, and suggest that graptolite fossils, which occur worldwide, warrant further investigation. Much later, X-ray absorption near edge structure (XANES) spectromicroscopy showed organic functional group distributions in Paleozoic scorpion and false scorpion exoskeletons that were consistent with original chitin and chitin-associated protein [108].
Glimpses into the molecular pathogenesis of Peyronie’s disease
Published in The Aging Male, 2020
Evert-Jan P. M. ten Dam, Mels F. van Driel, Igle Jan de Jong, Paul M. N. Werker, Ruud A. Bank
Collagen synthesis is a complex process, and many enzymes are involved. Chaperones assist in folding of the procollagen molecules and propeptidases cleave off the propeptides to convert procollagen into collagen. Conversion of proline into 3-hydroxyproline or 4-hydroxyproline is catalyzed by prolyl hydroxylases, conversion of lysine (Lys) into 4-hydroxylysine (Hyl) by lysyl hydroxylases, and cross-linking is initiated by lysyl oxidases [47]. We used a low-density array (Table 2 andFigure 3) to quantify the expression of these enzymes, to clarify whether there were possible aberrations in (pro)collagen processing. An important post-translational modification of collagen is the conversion of triple helical lysine (Lys) into hydroxylysine (Hyl), and the addition of sugars to Hyl, resulting in the glycosylated residues galactosylhydroxylysine (Gal–Hyl) and glucosylgalactosylhydroxylysine (Glc–Gal–Hyl) [26]. It has now been established that the conversion of triple helical Lys into Hyl is catalyzed by lysyl hydroxylase 1 (encoded by PLOD1) and lysyl hydroxylase 3 (encoded by PLOD3), and that the formation of Glc–Gal–Hyl (but not Gal-Hyl) is catalyzed by lysyl hydroxylase 3 [26]. We have observed no differences in mRNA levels of PLOD1 between plaque and control tissue, but there was a major increase in mRNA levels of PLOD3 in plaque tissue. Therefore, an overhydroxylation of Lys in PD tissue is expected, as well as increased levels of Glc–Gal–Hyl. A Lys overhydroxylation and a Hyl overglycosylation have been reported for affected DD tissues [37,40,41].
Related Knowledge Centers
- Collagen
- Lysine
- Amino Acid
- Hydroxy Group
- Lysyl Hydroxylase