Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reaction rates in metabolic pathways typically exhibit a kind of diminishing returns in which small variations in the activities of the individual enzymes have very little effect on overall flux. These effects are measured by the control coefficients of the enzymes, and most systems are governed by the summation theorem stating that all control coefficients must sum to unity. One implication is that complex systems will not usually contain single rate limiting steps, but rather be controlled to a greater or lesser extent by many enzymes, each exerting relatively small control. Wright understood this principle in 1934 and used it for his physiological theory of dominance. With respect to small variations in enzyme activity, the principle implies that many small variations should have only mild effects on fitness. Analysis of nucleotide polymorphisms in the genes for glucose-6-phosphate dehydrogenase and alkaline phosphatase in Escherichia coli implies that most amino acid replacements are harmful, and that the average selection coefficient against amino acid replacements that are polymorphic in natural populations is 1 x 10(-7) to 5 x 10(-7). In experiments to determine the a priori distribution of selection coefficients among random amino acid replacements, 25 replacements in beta-galactosidase were created by genetic means, and 22 of these produced selective effects too small to be detected in chemostat competition experiments (s less than 0.004 per generation).
 ...
PMID:The physiology of weak selection. 268 89

Photobacterium sp. strain SS9 is a deep-sea bacterium which modulates the abundances of several outer membrane proteins as a function of hydrostatic pressure. These proteins include the product of the previously cloned ompH gene (D. H. Bartlett, M. Wright, A. A. Yayanos, and M. Silverman. Nature (London) 342:572-574, 1989). Subsequent to conjugal plasmid delivery it was possible to cross an ompH::lacZ transcriptional fusion into the genome of SS9, replacing the wild-type ompH gene, generating strain EC10. EC10 is not impaired in growth at high pressure, indicating that under the growth conditions employed, OmpH is not required for baroadaptation. beta-Galactosidase production in EC10 is induced by high pressure to approximately the same extent that OmpH production is in the parental strain, SS9. Therefore, OmpH abundance appears to be primarily regulated at the transcriptional level. EC10 was used for the isolation of ompH regulatory mutants. Derivatives of EC10 which produce reduced levels of beta-galactosidase at both low and high pressure and which appeared to possess mutations outside the ompH::lacZ locus were obtained. All of these regulatory mutants displayed alterations in the high-pressure repression of a second outer membrane protein, designated OmpL, and two of the mutants were also deficient in the high-pressure induction of a third outer membrane protein, designated OmpI. The most dramatic phenotype was present in mutant EC1002, whose growth was extremely barosensitive. EC1002 is the first pressure-sensitive mutant ever isolated. Prolonged incubation of EC1002 at high pressure led to the accumulation of cells with wild-type growth characteristics at high pressure. These cells are suggested to possess suppressor mutations, as they remain deficient in beta-galactosidase production and maintain their high-pressure-adapted phenotype for many generations in the absence of high-pressure selection.
 ...
PMID:Use of a reporter gene to follow high-pressure signal transduction in the deep-sea bacterium Photobacterium sp. strain SS9. 824 22

It has been proposed that the Xenopus homeobox gene, XlHbox8, is involved in endodermal differentiation during pancreatic and duodenal development (Wright, C.V.E., Schnegelsberg, P. and De Robertis, E.M. (1988). Development 105, 787-794). To test this hypothesis directly, gene targeting was used to make two different null mutations in the mouse XlHbox8 homolog, pdx-1. In the first, the second pdx-1 exon, including the homeobox, was replaced by a neomycin resistance cassette. In the second, a lacZ reporter was fused in-frame with the N terminus of PDX-1, replacing most of the homeodomain. Neonatal pdx-1 -/- mice are apancreatic, in confirmation of previous reports (Jonsson, J., Carlsson, L., Edlund, T. and Edlund, H. (1994). Nature 371, 606-609). However, the pancreatic buds do form in homozygous mutants, and the dorsal bud undergoes limited proliferation and outgrowth to form a small, irregularly branched, ductular tree. This outgrowth does not contain insulin or amylase-positive cells, but glucagon-expressing cells are found. The rostral duodenum shows a local absence of the normal columnar epithelial lining, villi, and Brunner's glands, which are replaced by a GLUT2-positive cuboidal epithelium resembling the bile duct lining. Just distal of the abnormal epithelium, the numbers of enteroendocrine cells in the villi are greatly reduced. The PDX-1/beta-galactosidase fusion allele is expressed in pancreatic and duodenal cells in the absence of functional PDX-1, with expression continuing into perinatal stages with similar boundaries and expression levels. These results offer additional insight into the role of pdx-1 in the determination and differentiation of the posterior foregut, particularly regarding the proliferation and differentiation of the pancreatic progenitors.
 ...
PMID:PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. 863 Dec 75