Disease relevance of ISODESMOSINE

• To measure the urinary excretion of specific cross-link amino acid markers for mature elastin (desmosine [DES] and isodesmosine [IDES]) and fibrillar collagen (hydroxylysylpyridinoline [HP] and lysylpyridinoline [LP]) in systemic sclerosis (SSc) patients and healthy controls [1].
• RESULTS: In the 17 patients with liver fibrosis score of 5-6, mean urinary DES, IDES, HP and LP were all significantly greater than in the control group (p<0.05) [2].
• The aim of this study was to evaluate the potential of urinary amino acids desmosine (DES) and isodesmosine (IDES) derived from the breakdown of elastin and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) derived from fibrillar collagen in diagnosing chronic liver disease [2].
• Urinary DES and IDES correlated best with fibrosis score, r=0.61 for both markers [2].
• Nevertheless, the relatively high specific radioactivity of DES + IDES in lung elastin as compared with urine makes monitoring labeled urinary DES + IDES in this animal model a sensitive tool for assessing elastin degradation in experimental lung disease [3].

High impact information on ISODESMOSINE

• Desmosine and isodesmosine, cross-linking compounds associated with mature elastin, were found in hydrolysates of the shell membrane, confirming the necessity for lysyl oxidase in its biosynthesis [4].
• Amino acid analyses of both elastin preparations indicated that the values for desmosine and isodesmosine were reduced in Marfan cases to approximately one-half of the control values [5].
• The detection and quantitation of free desmosine and isodesmosine in human urine and their peptide-bound forms in sputum [6].
• The DESP/desmosine (DES) and IDP/isodesmosine (IDE) ratios in aorta elastin were higher than in other tissues [7].
• We conclude that lung elastin is the most likely source of the increased DES and IDES in CF [8].

Chemical compound and disease context of ISODESMOSINE

• The alterated Ides to Des ratio suggests a primary disease of CPM as a cause of Zenker's diverticulum [9].
• 4-L-Hydroxyproline (HYP), as a marker of collagen content, and desmosine (DES) and isodesmosine (IDES), as markers of elastin, were measured in 47 macroscopically dilated and 32 nondilated segments of 20 varicose saphenous veins collected from 20 patients with varices [10].
• Measurement of cross-linked elastin synthesis in bleomycin-induced pulmonary fibrosis using a highly sensitive assay for desmosine and isodesmosine [11].

Biological context of ISODESMOSINE

• For the gravid subjects as a group and also for each subject, the mean values for urinary DES, IDES, HP, and HP/LP during the first 6 weeks postpartum were significantly greater than the mean baseline values beginning 27 weeks postpartum [12].
• We measured the urinary excretion of specific amino acid markers for mature elastin (desmosine [DES] and isodesmosine [IDES]) and fibrillar collagen (hydroxylysyl pyridinoline [HP] and lysyl pyridinoline [LP]) before and after parturition in three gravid subjects [12].
• 1. Desmosine and isodesmosine were separated by ion-exchange and paper chromatography, after acid hydrolysis of purified elastin from beef ligamentum nuchae [13].
• Intestinal absorption of desmosine and isodesmosine was investigated in several animal species [14].
• Comparing amino acid compositions of eggshells collected following oviposition with those collected from the same clutch after hatching reveals similarities among all eggshells except those of Eumeces from Michigan which lack desmosine and isodesmosine [15].

Anatomical context of ISODESMOSINE

• In the absence of beta-aminopropionitrile, long-term cultures of smooth muscle cells incorporated [14C]lysine into desmosine and isodesmosine, the cross-link amino acids unique to elastin [16].
• The differences in desmosine, isodesmosine (DID), hydroxyproline and cholesterol in the human thoracic aorta from diabetic (n = 16) and non-diabetic (n = 17) autopsy subjects were investigated [17].
• The organs with the highest DES + IDES-specific radioactivity at 12 months were heart-liver-kidney-spleen, lung, and gastrointestinal tract, with 310, 217, and 217 dpm/nmol, respectively [3].
• Desmosine and isodesmosine were of particular interest because of their importance in elastic fiber and the lack of highly sensitive HPLC methods for the determination of these compounds [18].
• Mature bovine Descemet's membrane contains desmosine and isodesmosine [19].

Associations of ISODESMOSINE with other chemical compounds

• Mean urinary excretion of elastin-derived crosslinks in the COPD group (DES, 11.8 +/- 5.1 [mean +/- SD]; IDES, 11.3 +/- 5.0 micrograms/g creatinine) and in the SM group (DES, 11.0 +/- 4.2; IDES, 10.2 +/- 2.5 micrograms/g creatinine) was significantly higher than in the NSM group (DES, 7.5 +/- 1.4; IDES, 6.9 +/- 1.3 micrograms/g creatinine) [20].
• Elastin and collagen were quantitated by measuring desmosine/isodesmosine and hydroxyproline spectrophometrically, respectively [21].
• Desmosine (Des) and its isomer isodesmosine (Isodes) are crosslinks specifically found in elastin [22].
• Since photolysis of desmosine and isodesmosine leads also to the formation of new lysine residues, methods will have to be devised to distinguish lysine-containing peptides derived from photolyzed elastin [23].
• The cross-links histidinoalanine (HA); pyridinoline (Pyr); desmosine (Des); and isodesmosine (Ides) in human atherosclerotic aortas were studied [24].

Gene context of ISODESMOSINE

• Elastin contains a number of cross-linking amino acid residues such as desmosine and isodesmosine which are primarily hydrophobic in character, but have a positively charged pyridinium ring [25].
• These are covalently cross-linked to form insoluble elastin by formation of desmosine and isodesmosine, catalysed by the enzyme lysyl oxidase [26].
• All the data presented are consistent with the scheme proposed for the formation of desmosine and isodesmosine cross-links of elastin by Gerber & Anwar [(1975) Biochem. J. 149, 685--695] [27].
• There was a significant reduction of both DES and IDES in dilated segments of varicose veins (P < 0.05 vs normal veins and nondilated segments); the ratio of elastin to collagen was lower in varicose than normal veins (P < 0.05), and this reduction was most significant in the dilated segments (P < 0.01 vs normal veins) [10].
• Also found were marked decreases in the aorta contents of desmosine and isodesmosine, which are cross-linking amino acids present only in the elastin [28].

Analytical, diagnostic and therapeutic context of ISODESMOSINE

• Urine specimens from 20 patients with SSc and 22 controls were assessed for DES, IDES, HP, and LP using high performance liquid chromatography and ultraviolet absorption spectroscopy, in combination with an isotope dilution technique in which the urine specimen was spiked with isotopically labeled cross-link amino acids [1].
• We developed a direct and one-injection HPLC method to measure Pyr, Dpyr, Des, Isodes, and Pen in the hydrolysate of human yellow ligament [29].
• Determination of desmosine, isodesmosine, and other amino acids by liquid chromatography with electrochemical detection following precolumn derivatization with naphthalenedialdehyde/cyanide [18].
• The desmosine fraction could be resolved into seven compounds and the isodesmosine into four by paper chromatography [13].
• Desmosine and isodesmosine as cross-links in the hinge-ligament protein of bivalves. 3,3'-Methylenebistyrosine as an artefact [30].

References