Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.9 (enterokinase)
 675 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral feeding of DL-difluoromethyl ornithine (DFMO) (2% in water ad libitum) for 14 days has no detectable effect on the small intestine of adult rats. Similar feeding of DFMO to weanling rat pups caused diarrhea in three to four days accompanied by a decrease in food consumption and body weight compared to age-matched controls. Significant decreases in small intestinal mucosal weight, total protein, DNA, enterokinase, leucine amino peptidase, sucrase, and maltase contents were observed in the DFMO-treated group four days after treatment. Extending the treatment to seven days led to a more severe reduction in these parameters. Villous atrophy of the mucosa was demonstrable by light microscopy and morphometric measurements. The mucosa of the DFMO-treated rat pups showed a reduction in total thickness and villous height but no change in crypt depth. A significant reduction in villus-crypt ratio was also seen. Changes in small intestinal mucosal parameters were not due to a decrease in food intake since pair-fed, age-matched rat pups showed no biochemical changes compared to control pups. DFMO-treated weanling rats showed less than 5% of ornithine decarboxylase (ODC) activity when compared to age-matched control animals. The effects observed on the small intestinal mucosa are presumably due to inhibition of ornithine decarboxylase activities by DFMO which prevents the proliferation, regeneration, and maturation of epithelial cells. The relative insensitivity of the adult rat small intestine to DFMO treatment suggests a lesser dependence of its intestinal mucosa to ODC activities.
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PMID:Effect of difluoromethyl ornithine (DFMO) on small intestine of adult and weanling rats. 311 4

Histidine 57 of the catalytic triad of trypsin was replaced with alanine to determine whether the resulting variant would be capable of substrate-assisted catalysis [Carter, P., & Wells, J. A. (1987) Science 237, 394-9]. A 2.5-fold increase in kcat/Km was observed on tri- or tetrapeptide substrates containing p-nitroanilide leaving groups and histidine at P2. In contrast, hydrolysis of peptide substrates extending from P6 to P6' is improved 70-300-fold by histidine in the P2 or P1' position. This preference creates new protease specificities for sequences HR decreases, R decreases H, HK decreases, and K decreases H. The ability of histidine from either the P2 or the P1' position of substrate to participate in catalysis emphasizes the considerable variability of proteolytically active orientations which can be assumed by the catalytic triad. Trypsin H57A is able to hydrolyze fully folded ornithine decarboxylase with complete specificity at a site containing the sequence HRH. Trypsin H57A was compared to enteropeptidase in its ability to cleave a propeptide from trypsinogen. Trypsin H57A cleaved the propeptide of a variant trypsinogen containing an introduced FPVDDDHR cleavage site only 100-fold slower than enteropeptidase cleaved trypsinogen. The selective cleavage of folded proteins suggests that trypsin H57A can be used for specific peptide and protein cleavage. The extension of substrate-assisted catalysis to the chymotrypsin family of proteolytic enzymes indicates that it may be possible to apply this strategy to a wide range of serine proteases and thereby develop various unique specificities for peptide and protein hydrolysis.
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PMID:Trypsin specificity increased through substrate-assisted catalysis. 754 82