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J H Gilchrist

Publications and source records attributed to J H Gilchrist.

4 recordsLinked to original sources
PubMed1992

Confirmation of genetic heterogeneity in limb-girdle muscular dystrophy: linkage of an autosomal dominant form to chromosome 5q.

Limb-girdle muscular dystrophy (LGMD) is a clinically and genetically heterogenous group of disorders, with both recessive and dominant forms reported. Recently, a series of recessive LGMD families were linked to chromosome 15q. We report herein the results of our linkage studies in a previously reported large autosomal dominant family. The LGMD gene in this family was localized to chromosome 5q22.3-31.3 by using a series of CA(n) microsatellite repeat markers. Linkage to 15q was excluded. These findings confirm genetic heterogeneity in this clinically diverse syndrome.

Cell Line, Transformed↗
PubMed1987

Electronic probes of the mechanism of substrate oxidation by buttermilk xanthine oxidase: role of the active-site nucleophile in oxidation.

Quinazolin-4(3H)-one derivatives substituted at the 6- and/or 7-position were studied as electronic probes of substrate oxidation by buttermilk xanthine oxidase. Since the enzyme active site possesses dimensional tolerance, the substituents exert an electronic effect rather than a steric effect on the catalytic parameters for oxidation. This feature permitted a Hammett plot to be made for quinazoline-oxygen substrate activity. The concave downward nature of this plot indicates that the rate-determining step for oxidation changes when electron-withdrawing substituents are placed on the substrate. This plot and kinetic isotope effects obtained with 2-deuterio derivatives of the substrates indicate the following: (i) oxidation involves nucleophile transfer to the C(2) center in concert with hydride transfer to the molybdenum center, and (ii) the formation of oxidized product is a three-step process, i.e., Michaelis complex formation, oxidation, and hydrolysis of the oxidized substrate-enzyme adduct. The role of the nucleophile in oxidation appears to be to increase the electron density in the substrate and thereby facilitate hydride transfer. The implication of this study is that similar electronic probes may be designed to study other purine-utilizing enzymes possessing a dimensionally tolerant active site.

Animals↗