The Noncollagenous Proteins of the Intervertebral Disc *
Peter Ghosh in The Biology of the Intervertebral Disc, 2019
Elastin is a highly insoluble protein rich in hydrophobic amino acids and contains few polar functional groups. It is synthesized as a soluble precursor molecule, tropoelastin (mol wt 72,000), of similar amino acid composition to insoluble elastin, but contains additional lysine residues which are subsequently involved in cross-link formation. These convert the tyopoelastin to insoluble elastin. Cross-linking is achieved via aldehyde (allysine) formation derived from lysine residues by the enzyme lysyloxidase. The cross-links of elastin contain the unique amino acids desmosine and isodesmosine.78,79 Other cross-links have recently been described,80–83 some of which are identical to those present in collagen.84 However, all of the known cross links of elastin are derived from lysine, whereas hydroxylysine is also utilized in collagen cross-link formation. In mature elastin, dihydrodesmosine and dihydroisodesmosine are more prevalent than the desmosine and isodesmosine ring structures. Problems, however, are encountered in the unequivocal demonstration of cross-linking structures in mature elastin, since the harsh extractive conditions required for its solubilization partially destroy desmosine/isodesmosine and intermediate cross-link structures.85,86
Introduction and Review of Biological Background
Luke R. Bucci in Nutrition Applied to Injury Rehabilitation and Sports Medicine, 2020
Elastins are very large, highly cross-linked proteins similar to collagens. Elastins form a three-dimensional mesh network in various tissues to give elastic, resilient properties to tissues. The mesh network can be stretched into almost parallel fibers, which return to their original shape. Elastins are rich in ligaments, skin, large blood vessels, and lungs, which are all tissues with the need for expansion and reversion to original shape. Because of the highly cross-linked structure of elastin meshes, turnover is very slow (months to years), and elastins are very resistant to degradation. Unlike collagens, elastins form desmosine, an amino acid unique to elastin, that forms covalent bonds for cross-links to adjacent elastin polypeptide chains. Some of the synthetic machinery used for collagen synthesis is also duplicated for elastin (such as prolyl hydroxylase), but there is no hydroxylation of lysine in elastin. For nutritional purposes, elastin synthesis relies on many of the same nutrient needs as collagen, but without the specific needs for copper or calcium (see Table 3).
Proteins for Conditioning Hair and Skin
Randy Schueller, Perry Romanowski in Conditioning Agents for Hair and Skin, 2020
Elastin is the second most common connective tissue protein after collagen, constituting 60-80% of the dry weight of blood vessels and ligaments. Its unique amino acids are desmosine and isodesmosine. In skin, elastin fibers enmeshed in collagen provide skin with its elastic strength (23). Excessive sun exposure leads to abnormal, disoriented elastin fibers and folding of the epidermis (i.e., wrinkles) (26). Like hydrolyzed collagen, hydrolyzed elastin of 2000 to 5000 Da is a good film former, but is much less hygroscopic due to its much lower polar and charged amino acid content (see Tables 2 and 3). As a result it has much higher hydroalcoholic and polyol solubility and can reduce swelling of hair during permanent waving and coloring processes. Like other low-polarity protein hydrolyzates, such as silk (17), it may be preferable to collagen (and other more hydrophilic hydrolyzates) where humidity resistance is desirable.
Blood and sputum protein biomarkers for chronic obstructive pulmonary disease (COPD)
Published in Expert Review of Proteomics, 2018
Ji-Yong Moon, Fernando Sergio Leitao Filho, Kimeya Shahangian, Hiroto Takiguchi, Don D. Sin
Neutrophil elastase (NE) is a serine protease stored in azurophilic granules within neutrophils. Apart from its role in the immune system, NE is also involved in the turnover of the extracellular matrix (ECM) and has been implicated in lung elastin degradation [66]. This proteinase is inhibited by alpha-1 anti-trypsin (AAT), explaining why a disruption in the protease/antiprotease balance could promote the destruction of alveolar structures, ultimately leading to emphysema [67]. NE-mediated elastin degradation can occur not only in patients with alpha-1 anti-trypsin deficiency (AATD) but also in other COPD patients due to the inactivation of AAT through the presence of smoking-induced oxidants [68]. Products of elastin degradation, namely desmosine and isodesmosine (DI), may be surrogates of NE activity and elastin degradation [69]. DI levels are significantly elevated in the sputum of COPD patients with AATD, and COPD patients with normal AAT levels may also present with higher sputum DI levels compared to healthy controls [70]. Moreover, alpha-1 antitrypsin augmentation therapy has been shown to decrease plasma levels of DI [71,72], suggesting that this protein could be used as a biomarker to monitor emphysema progression and evaluate treatment response.
Experimental and investigational drugs for the treatment of alpha-1 antitrypsin deficiency
Published in Expert Opinion on Investigational Drugs, 2019
As described in the introduction protease imbalance plays a key role in lung disease pathogenesis in AATD, driven by the lack of inhibition of NE by AAT. In addition, intravenous augmentation therapy, which appears clinically beneficial, reduces markers of NE activity (desmosine) [34], further confirming the importance of this pathway. Alvelestat (MPH-996), an oral NE inhibitor, is currently being trialed in Phase 2 clinical trials ASTRAEUS (NCT03636347) and ATALANTa (NCT03679598) which aim to reduce lung damage and slow the progression of lung disease caused by AATD. The primary endpoint is the change from baseline of desmosine/isodesmosine as biomarkers of NE activity. The rarity of AATD, and consequent need for surrogate outcomes if a study is to be of a reasonable size, has made markers like desmosine attractive as a primary outcome for phase 2 studies treating AATD lung disease.
Association between serum elastin-derived peptides and abdominal aortic calcification in peritoneal dialysis patients: a cross-sectional study
Published in Renal Failure, 2021
Shizhu Zhao, Jingyuan Cao, Jianzhong Li, Xiaochun Yang, Peiyang Cao, Jingjing Lan, Guoyuan Lu
Elastin degradation participates in the pathogenesis of atherosclerosis and medial calcification [25,26], both of which coexist in CKD. EDPs in CKD patients were significantly higher than in controls and were associated with increased aortic stiffness and all-cause mortality [27]. Desmosine was also found to correlate with coronary artery calcification rather than emphysema in patients with COPD [28], indicating EDPs was more relevant to elastin of the vascular rather than the lungs. Apart from that, circulating EDPs were also considerably elevated in diabetes with microvascular complications such as albuminuria and retinopathy [29]. Similar to those researches of strong correlation between EDPs and vascular disease, we found serum EDPs was significantly higher in PD patients with AAC, and it increased as the calcificaiton worsened. Further, elevated EDPs was a vital factor related to the risk of AAC and severe AAC in PD patients, prompting its important role in AAC risk stratification.
Related Knowledge Centers
- Alanine
- Elastic Artery
- Elastin
- Lysine
- Mass Spectrometry
- Connective Tissue
- Lung
- Skin
- Isodesmosine
- Pyridinium