Disease relevance of Isomerism

• Gdf1-/- mice exhibited a spectrum of defects related to left-right axis formation, including visceral situs inversus, right pulmonary isomerism and a range of cardiac anomalies [1].
• In a 3-year period, three of the six cases of left isomerism sequence notified to the Northern Region Congenital Abnormality Survey were the infants of diabetic mothers [2].
• Structural characterization of the HIV-1 Vpr N terminus: evidence of cis/trans-proline isomerism [3].
• Associated cardiac lesions included single atrium, absence of the coronary sinus, bilateral superior venae cavae, absence of the hepatic segment of the inferior vena cava with azygos and hemiazygos continuation, right aortic arch, levocardia and left atrial isomerism [4].
• An 8-month-old boy with double outlet right ventricle with hypoplastic left ventricle, heterotaxy, left atrial isomerism, bilateral superior vena cavae without bridging vein, and interruption of the inferior vena cava with azygous continuation to the left superior cava underwent a bilateral bidirectional cavopulmonary anastomosis [5].

High impact information on Isomerism

• Misexpression of Pitx2 on the right side of the embryo is sufficient to produce reversed heart looping and heart isomerisms, reversed body rotation, and reversed gut situs [6].
• Unexpectedly, however, the most common feature of lefty-1-/- mice was thoracic left isomerism (rather than right isomerism) [7].
• Many molecules can rotate freely around single bonds and thereby interconvert between different conformations, such as gauche and anti 1,2-disubstituted ethane, a classic example of conformational isomerism [8].
• These observations led us to hypothesize that cis/trans isomerism at a single peptide bond between a proline and its preceding residue might be the origin of the conformational multiplicity [9].
• Here, we show that a proportion of embryos lacking SPC4 develop situs ambiguus combined with left pulmonary isomerism or complex craniofacial malformations including cyclopia, or both [10].

Biological context of Isomerism

• None of the left-right patterning abnormalities and organogenesis defects identified in mice carrying mutations in Nodal or in genes encoding ActRIIA and ActRIIB coreceptors, including heart malformations, pulmonary isomerism, right-sided gut, and spleen hypoplasia, were observed in mice lacking ALK7 [11].
• Proline isomerism in the protein folding of ribonuclease A [12].
• In cases of morphologically distinguishable right atrial appendage isomerism, both atrial appendages show strong transgene expression [13].
• Kinetics and mechanisms of thioamide rotational isomerism: N-thionaphthoyl-N-methyl glycine derivative [14].
• Among the enzymes used, only Proteinase K could recognize the isomerism of DMO, resulting in the following order of degradability: copoly(L-DMO/CL) > copoly(DL-DMO/CL) > copoly(D-DMO/CL), i.e. this enzyme has the highest substrate specificity for naturally occurring L-alanine [15].

Anatomical context of Isomerism

• Mouse Pitx2 deficiency leads to anomalies of the ventral body wall, heart, extra- and periocular mesoderm and right pulmonary isomerism [16].
• Left ventricular structures in atrioventricular septal defect associated with isomerism of atrial appendages compared with similar features with usual atrial arrangement [17].
• It has been demonstrated that triacylglycerol (TAG) mobilization from adipose tissue is selective and depends on fatty acid (FA) chain length, unsaturation and positional isomerism [18].
• One patient had right atrial isomerism manifested by asplenia and a common atrium, into which the hepatic veins drained directly, and the other patient had left atrial isomerism manifested by polysplenia, a common atrium, and a ventricular septal defect with a single atrioventricular valve [19].
• Situs ambiguus, especially left isomerism, is frequently associated with deteriorated sinus node function, and an interruption of the inferior vena cava may also be an indication of this phenomenon [20].

Associations of Isomerism with chemical compounds

• Rotational isomerism about the 17(20)-bond of steroids and euphoids as shown by the crystal structures of euphol and tirucallol [21].
• Structural variations include: constitutional isomerism of the vinyl or carboxyethyl side chains, geometric isomerism of the methene bridges, tautomerism of the lactam groups, conformational rotations about the central methylene bridge and ionization of one or both carboxyl groups [22].
• To probe a possible functional role of the Leu(12)-Pro(13) cis/trans isomerism, a Pro(13) --> Ala delta-conotoxin EVIA was synthesized and shown to exist only as a trans isomer [23].
• Double bond isomerism could also be distinguished; oleic acid (18:1cis) induced a net disordering effect, whereas elaidic acid (18:1trans) produced no changes in GP [24].
• The slow kinetic phase is evidently due to this effect of Fe(III) and not to the slow cis-trans isomerism of the peptide bond of proline residues as has been suggested [25].

Gene context of Isomerism

• Cited2 is also required for normal establishment of the left-right axis; we demonstrate that abnormal heart looping and right atrial and pulmonary isomerism are consistent features of the left-right-patterning defect [26].
• Targeted disruption of murine Cryptic results in L-R laterality defects including randomization of abdominal situs, hyposplenia, and pulmonary right isomerism, as well as randomized embryo turning and cardiac looping [27].
• We show that mouse embryos lacking Shh display a variety of laterality defects, including pulmonary left isomerism, alterations of heart looping, and randomization of axial turning [28].
• In addition, NMR data revealed that all of the proline residues undergo a cis/ trans isomerism to such an extent that approximately 40% of all Vpr molecules possess at least one proline in a cis conformation [3].
• We have shown previously that mice deficient in the activin type IIB receptor (ActRIIB) exhibit right isomerism, which is characterized by mirror-image symmetrical right lungs, complex cardiac malformations, and hypoplasia of the spleen [29].

Analytical, diagnostic and therapeutic context of Isomerism

• Proline isomerism in staphylococcal nuclease characterized by NMR and site-directed mutagenesis [9].
• Bidirectional cavopulmonary anastomosis using vertical vein for right isomerism, pulmonary atresia, and TAPVR [30].
• To investigate the importance of amino acid residues in the central region between the inner cysteines and at the carboxy terminus for this isomerism, synthetic derivatives of guanylin were compared by HPLC, 2D1H NMR spectroscopy and by their guanylyl cyclase-C (GC-C)-activating potency [31].
• Radionuclide angiography of azygos continuation of inferior vena cava in left atrial isomerism (polysplenia syndrome) [32].
• METHODS AND RESULTS: Between January 1990 and February 2004, 83 of 166 cases (50%) had a prenatal diagnosis of left isomerism (LAI; 52 of 97) or right isomerism (RAI; 31 of 69) at our institution [33].

References