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61.
Unusual clustering of diseases in a Canadian Old Colony (Chortitza) Mennonite kindred and community.
M A Jaworski J D Slater A Severini K R Hennig G Mansour J G Mehta R Jeske J Schlaut C Y Pak J W Yoon 《CMAJ》1988,138(11):1017-1025
We investigated a large Old Colony (Chortitza) Mennonite kindred with branches across Canada. Six generations of the kindred were traced. There was intermarriage among numerous family members. Insulin-dependent diabetes mellitus (IDDM) was identified in 10 members; all 7 living patients were found to carry the immunogenetic marker HLA-DR4. Nine other close relatives had disorders of carbohydrate metabolism, including gestational diabetes mellitus and non-insulin-dependent diabetes mellitus progressing to insulin use. Ten other relatives had autoimmune diseases, including rheumatoid arthritis, hyperthyroidism, hypothyroidism and multiple sclerosis. Cases of Alport''s syndrome, congenital malformations, inborn errors of metabolism and unusual malignant diseases were also found in the kindred. In the small Alberta community in which the kindred was ascertained there were people of Old Colony Mennonite descent with genetic conditions such as Gilles de la Tourette''s syndrome and congenital malformations, including congenital heart disease. This kindred represents the largest reported familial aggregation of IDDM. This disease and other disorders of carbohydrate metabolism occur in the context of a strong familial predisposition to autoimmune disease. Study of this family may permit empiric testing of proposed models of inheritance of diseases of complex origin such as IDDM. We report this Old Colony (Chortitza) Mennonite community because it is one of the settlements populated by this religious and genetic isolate, which extends across Canada and Central and South America and affords opportunities for the study of both common and rare inherited diseases. 相似文献
62.
Synthesis of radiolabeled acetyl-coenzyme A from sodium acetate 总被引:3,自引:0,他引:3
The synthesis of high specific radioactivity [14C]-acetyl-Coenzyme A from [14C]sodium acetate, 2,6-dichlorobenzoic acid, 1,1'-carbonyldiimidazole, and CoA is reported. Starting with 1 mumol of [14C]sodium acetate, this method yields pure [14C]acetyl-CoA in yields approaching 40%. Chromatography on a reversed-phase ODS column was used to separate acetyl-CoA from Coenzyme A and side products. The acetylating agent is apparently a reaction intermediate, acetylimidazole. 相似文献
63.
Site-directed mutagenesis of the spinach acyl carrier protein-I prosthetic group attachment site 总被引:3,自引:0,他引:3
J G Jaworski M A Post-Beittenmiller J B Ohlrogge 《European journal of biochemistry》1989,184(3):603-609
Site-directed mutagenesis was used to change the phosphopantetheine attachment site (Ser38) of spinach acyl carrier protein I (ACP-I) from a serine to a threonine or cysteine residue. 1. Although the native ACP-I is fully phosphopantethenylated when expressed in Escherichia coli, the TH-ACP-I and CY-ACP-I mutants were found to be completely devoid of the phosphopantetheine group. Therefore, the E. coli holoACP synthase requires serine for in vivo phosphopantetheine addition to spinach ACP-I. 2. Spinach holoACP synthase was completely inactive in vitro with either the TH-ACP-I or CY-ACP-I mutants. In addition, TH-ACP-I and CY-ACP-I were strong inhibitors of spinach holoACP synthase. 3. The mutant ACPs were weak or ineffective as inhibitors of spinach fatty acid synthesis and spinach oleoyl-ACP hydrolase. 4. Compared to holoACP-I, the mutant apoACP-I analogs had: (a) altered mobility in SDS and native gel electrophoresis, (b) altered binding to anti-(spinach ACP-I) antibodies and (c) altered isoelectric points. The combined physical, immunological and enzyme inhibition data indicate that attachment of the phosphopantheine prosthetic group alters ACP conformation. 相似文献
64.
Transformation of steroids by fungal protoplasts 总被引:4,自引:0,他引:4
Leon Sedlaczek Jerzy Długoński Adam Jaworski 《Applied microbiology and biotechnology》1984,20(3):166-169
Summary Protoplasts of Cunninghamella elegans transformed cortexolone to the same products as did the mycelium. Transformation of the steroid by non-induced mycelium and by protoplasts released from it was almost completely inhibited by cycloheximide. However, hydroxylation of cortexolone was not affected by this antibiotic if mycelium grown in the presence of an enzyme inducer or protoplasts obtained from the induced mycelium were used. The transformation rate of protoplasts, on the basis of dry weight or protein units, was about four times higher than that of the mycelium, indicating that the mycelial cell wall was a serious rate-limiting factor in steroid bioconversion. 相似文献
65.
Agarose and polyacrylamide gel electrophoresis of a total alpaca (Lama pacos) DNA, digested with several restriction enzymes, revealed the presence of two tandemly organized repetitive DNA sequences, named Satellite I and Satellite II. Three Xhol-monomers from Satellite I DNA and two BspRI-monomers from Satellite II DNA were sequenced. As determined by dot hybridization analysis, the total alpaca DNA consists of 3.4% and 1.3% Satellites I and II, respectively. Computer search revealed no homology to any primate, rodent or mammalian sequences published in the Gen Bank Release 48.0 (February 1987) and the EMBL Bank Release 10 (December 1986). 相似文献
66.
67.
In vivo pools of free and acylated acyl carrier proteins in spinach. Evidence for sites of regulation of fatty acid biosynthesis 总被引:17,自引:0,他引:17
D Post-Beittenmiller J G Jaworski J B Ohlrogge 《The Journal of biological chemistry》1991,266(3):1858-1865
In order to examine potential regulatory steps in plant fatty acid biosynthesis, we have developed procedures for the analysis of the major acyl-acyl carrier protein (ACP) intermediates of this pathway. These techniques have been used to separate and identify acyl-ACPs with chain configurations ranging from 2:0 to 18:1 and to determine the relative in vivo concentrations of acyl-ACPs in spinach leaf and developing seed. In both leaf and seed as much as 60% of the total ACPs were nonesterified (free), with the remaining proportion consisting of acyl-ACP intermediates leading to the formation of palmitate, stearate, and oleate. In spinach leaf the proportions of the various acyl groups esterified to each ACP isoform were indistinguishable, indicating that these isoforms are utilized similarly in de novo fatty acid biosynthesis in vivo. However, the acyl group distribution pattern of seed ACP-II differed significantly from that of leaf ACP-II. The malonyl-ACP levels were less than the 4:0-ACP and 6:0-ACP levels in leaf, and in contrast, the malonyl-ACP-II levels in seed were approximately 3-fold higher than the 4:0-ACP-II and 6:0-ACP-II levels. In addition, the ratio of oleoyl-ACP-II (18:1) to stearoyl-ACP-II (18:0) was higher in seed than in leaf. These data suggest that the differences in acyl-ACP patterns reflect a tissue/organ-specific difference rather than an isoform-specific difference. In extracts prepared from leaf samples collected in the dark, the levels of acetyl-ACPs were approximately 5-fold higher compared to samples collected in the light. The levels of free ACPs showed an inverse response, increasing in the light and decreasing in the dark. Notably there was no concomitant increase in the malonyl-ACP levels. The most likely explanation for the major increase in acetyl-ACP levels in the dark is that light/dark control over the rate of fatty acid biosynthesis occurs at the reaction catalyzed by acetyl-CoA carboxylase. 相似文献
68.
Oleoyl-CoA is not an immediate substrate for fatty acid elongation in developing seeds of Brassica napus 总被引:1,自引:1,他引:0
Alenka Hlousek-Radojcic Hiroyuki Imai Jan G. Jaworski 《The Plant journal : for cell and molecular biology》1995,8(6):803-809
The substrate specificity of fatty acid elongase was studied using an oil body fraction from developing seeds of Brassica napus. ATP was essential for high rates of elongase activity, but there was no apparent requirement for oleoyl-CoA, oleic acid (18:1) or CoA. Furthermore, 14C from 18:1-CoA was incorporated into eicosenoic (20:1) and erucic (22:1) acids at a much slower rate than 14C from malonyl-CoA. Incubation of [14C]18:1-CoA with the oil body fraction resulted in a rapid loss of [14C]18:1-CoA into several lipid fractions whether in the absence or presence of ATP, but the loss of 18:1-CoA had a comparatively small effect on the overall rate of elongation. Acyl-CoAs were derivatized to their respective acylbutylamide and analyzed by gas chromatography-mass spectrometry. This analysis of acyl-CoAs demonstrated that there was no detectable 20:1-CoA or 22:1-CoA at 0 min incubation, while newly synthesized 20:1-CoA and 22:1-CoA were present at 10 min. Analysis of the %14C of the substrates and products of the elongation reaction revealed that the endogenous pool of 18:1-CoA is quite small in elongase preparations. In addition, [14C]18:1-CoA added to the incubation, although incorporated into lipids, was not significantly diluted by turnover or new synthesis. In contrast, the %14C of the 20:1-CoA was two- to threefold less than that of the 18:1-CoA. Taken together, these results indicate that the [14C]18:1 from the [14C]18:1-CoA was diluted in an intermediate 18:1 pool and that the 18:1-CoA was not the major donor of the acyl group to the elongase reaction. 相似文献
69.
70.