Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new hereditary defect of tryptophan metabolism is described in a Sudanese family with a high degree of consanguinity. It has an autosomal recessive pattern of inheritance. The condition manifests as a pellagra-like skin rash within 8 weeks after birth, with signs of cerebellar ataxia and developmental retardation. Cataracts develop early, and to date none of the ten affected children has survived beyond 2 years of age. Biochemically, the condition is characterized by an apparent impairment of the ability to synthesize quinolinic acid and nicotinamide nucleotides from tryptophan, which might be due to abnormally high activity of the enzyme picolinate carboxylase.
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PMID:Lethal familial pellagra-like skin lesion associated with neurologic and developmental impairment and the development of cataracts. 405 88

The three major bovine gamma-crystallin fractions (gamma-II, gamma-III and gamma-IV) are known to have closely related (80-90%) amino acid sequences and three-dimensional folding of the polypeptide backbone. Their chiroptical and emission properties, as measured by circular dichroism (CD) and fluorescence, are now shown to differ distinctly. The far-ultraviolet CD spectra indicate that all three gamma-crystallins have predominantly beta-sheet conformation (45-60%) with only subtle differences in secondary structure. The fluorescence emission maxima of gamma-II, gamma-III and gamma-IV, due to the four tryptophan residues, appear at 324, 329 and 334 nm, respectively, suggesting that tryptophan residues are buried in environments of decreasing hydrophobicity. Corresponding differences in quantum yield may be due to fluorescence quenching by neighboring sulfur-containing residues. Titratable tyrosines are maximal for gamma-III, as manifested from difference absorption spectra at alkaline pH. The near-ultraviolet CD spectra differ in position, magnitude and sign of tryptophan and tyrosine transitions. In addition, a characteristic CD maximum at 235 nm, presumably due to tyrosine-tyrosine exciton interactions, differs in magnitude for each gamma-crystallin. This study shows that the environment and interactions of the aromatic residues of the individual gamma-crystallin fractions are quite different. These variations in tertiary structure may be significant, in terms of stability of gamma-crystallins towards aggregation and denaturation, for understanding lens transparency and cataract formation in general.
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PMID:Structure and stability of gamma-crystallins. I. Spectroscopic evaluation of secondary and tertiary structure in solution. 406 74

21 amino acids have been determined in aqueous humor obtained during microsurgical intraocular procedures in 30 patients with senile cataract and 27 patients with primary open-angle glaucoma. All individual amino acids showed higher levels in the glaucomas than in the cataracts: this is valid at 2p less than 0.05 for threonine, serine, asparagine, glutamine, methionine, tyrosine, phenylalanine, histidine, tryptophan, and arginine.
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PMID:Amino acid pattern in human aqueous humor of patients with senile cataract and primary open-angle glaucoma. 406 71

Human cataract lens crystallins are crosslinked and demonstrate a non-tryptophan blue fluorescence. We report here that exposure of lens crystallin to H2O2 within the concentration range reported for human aqueous humor, produces crosslinking of crystallin polypeptides within 10 minutes in the presence of the heme-undecapeptide from cytochrome c. Concomitantly, a blue fluorescence develops. These findings suggest the possibility that under some conditions hydrogen peroxide activation may play a role in cataractogenesis in vivo.
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PMID:The rapid H2O2-mediated nonphotodynamic crosslinking of lens crystallins generated by the heme-undecapeptide from cytochrome C: potential implications for cataractogenesis in man. 630 94

In this review some of the so far identified mechanisms implicated in experimental and human cataractogenesis are reviewed. The oxidative insult, the osmotic insult (sugar cataracts and ionic imbalance cataracts), the role of tryptophan, of lysophosphatidylcholine and docohexanoic acid in primary and secondary cataracts are summarized. It is not always possible to identify the primary effect of cataractogenic mechanisms: the human "idiopathic" cataract is probably a multifactorial disease. In the aging lens and under stress conditions (osmotic and oxidative) the physiologic defense systems of the lens appear to be inadequate. Even if conditions of avitaminosis aren't the cause of deterioration of the adult human lens, it has been demonstrated that the supplementation or the deficiency of some nutritional factors may influence the course of cataract.
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PMID:The physiologic and pharmacologic factors protecting the lens transparency and the update approach to the prevention of experimental cataracts: a review. 636 46

With aging and cataract formation, modifications in absorption and fluorescence of the human lens proteins are observed. These changes have been investigated by the examination of the endopeptidase-resistant fraction isolated from human cataractous lenses. This fraction is highly enriched in atypical fluorescence and absorption (i.e. not attributable to tryptophan, tyrosine or phenylalanine). It has a molecular weight of approximately 3000, is enriched in acidic amino acids and has only a 280 nm shoulder in its u.v. spectrum. The material does not contain detectable levels of malondialdehyde or N-formylkynurenine. Upon acid hydrolysis the fluorescence and u.v. spectra remain unchanged with only a minor degree of cleavage observed. Structural studies on some of the cleavage products indicated the presence of oxindolyl alanine and kynurenine. These compounds could result from photo-oxidation of tryptophan.
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PMID:The endopeptidase-resistant protein fraction from human cataractous lenses. 638 57

Female rats were fed defined diets limiting in one or more of certain amino acids and with or without vitamin E throughout gestation and lactation. Deficits of tryptophan, phenylalanine/tyrosine, or methionine/cystine reduced the body weight of progeny to about 50% or less of normal but only low tryptophan was cataractogenic. When total dietary amino acids were 12.4%, a low (65 mg%) level of tryptophan resulted in 34% incidence of cataract if vitamin E was simultaneously withheld. Elevation of total amino acids to 24.8% while maintaining tryptophan at 65 mg% caused 70 or 90% incidence of nuclear lens opacities in the presence or absence, respectively, of vitamin E. Maternal dietary amino acid imbalance was also associated with a 50% decrease in lens insoluble (membrane) proteins in the progeny independent of dietary vitamin E or the occurrence of opacities.
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PMID:Cataract formation following limited amino acid intake during gestation and lactation. 646 60

In vitro experimental evidence suggests tryptophan (TRP) is involved in protein modifications which could cause cataract formation in vivo. Previous studies of tryptophan plasma and serum metabolism are conflicting. In this study free and bound TRP plasma levels were measured in patients with senile cataract and in controls after an oral load of L-TRP (20 mg/kg b.w.). Free TRP levels were higher in patients than in controls one hour after L-TRP administration.
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PMID:Alteration of serum tryptophan metabolism in patients suffering from senile cataract. 652 24

In vitro experiments were performed in order to understand the biochemistry of tryptophan-deficient cataract. Eleven-day-old embryonic chick lenses were cultured in vitro for 3 hr, one and three days in a tryptophan-deficient medium. DNA breakage was followed on sucrose gradient and water-soluble protein synthesis was analysed by SDS-PAGE coupled with fluorography. A medium lacking tryptophan delays the DNA degradation and decreases the synthesis of all soluble proteins including the crystallins.
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PMID:Changes in the DNA breakage and crystallin synthesis of embryonic chicken lenses cultured in a tryptophan-deficient medium. 670 42

Soluble crystallins were isolated, by gel filtration, from the nucleus and cortex of types I-IV cataractous lenses and neonatal lenses. Extinction coefficients were determined and used to calculate the proportion of the crystallins. alpha Crystallins were the major proteins in the cortex of the cataractous lens whereas beta crystallins predominate in the nucleus and in the neonatal lens. Electrophoretic and immunological data, indicated that there was very little soluble gamma crystallin in the cataractous tissue. Highly specific competitive radioimmunoassays were used to estimate the crystallin contents of the various extracts. Values obtained for the neonatal extracts agreed closely with those from gel filtration but, in general, the values found for the cataractous proteins were low. The immunological reactivity of beta crystallin decreased progressively with the development of nuclear colour whereas alpha crystallin reactivity decreased sharply with the onset of nuclear cataract (type II lens) and then partially recovered. No significant alterations were found in the micro-environments of tryptophan residues in any of the proteins indicating that there are no gross conformational changes in the soluble proteins during cataract development. It would appear that the losses of immunochemical reactivity are due to chemical and/or conformational alterations which are restricted to the surface of the protein molecules.
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PMID:Conformational changes in soluble lens proteins during the development of senile nuclear cataract. 671 56


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