PubMed:7744780 JSONTXT

{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":119},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":120,"end":344},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":345,"end":533},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":534,"end":763},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":764,"end":1051},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":1052,"end":1305},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":1306,"end":1512},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":119},"obj":"Sentence"},{"id":"T2","span":{"begin":120,"end":344},"obj":"Sentence"},{"id":"T3","span":{"begin":345,"end":533},"obj":"Sentence"},{"id":"T4","span":{"begin":534,"end":763},"obj":"Sentence"},{"id":"T5","span":{"begin":764,"end":1051},"obj":"Sentence"},{"id":"T6","span":{"begin":1052,"end":1305},"obj":"Sentence"},{"id":"T7","span":{"begin":1306,"end":1512},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":120,"end":135},"obj":"gene:183"},{"id":"T1","span":{"begin":185,"end":207},"obj":"disease:C0085580"},{"id":"T2","span":{"begin":120,"end":135},"obj":"gene:183"},{"id":"T3","span":{"begin":235,"end":256},"obj":"disease:C0020538"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"7744780-1#0#15#gene183","span":{"begin":120,"end":135},"obj":"gene183"},{"id":"7744780-1#65#87#diseaseC0085580","span":{"begin":185,"end":207},"obj":"diseaseC0085580"},{"id":"7744780-1#115#136#diseaseC0020538","span":{"begin":235,"end":256},"obj":"diseaseC0020538"}],"relations":[{"id":"0#15#gene18365#87#diseaseC0085580","pred":"associated_with","subj":"7744780-1#0#15#gene183","obj":"7744780-1#65#87#diseaseC0085580"},{"id":"0#15#gene183115#136#diseaseC0020538","pred":"associated_with","subj":"7744780-1#0#15#gene183","obj":"7744780-1#115#136#diseaseC0020538"}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}

{"project":"Preeclampsia","denotations":[{"id":"PD-Preeclampsia-B_T1","span":{"begin":48,"end":60},"obj":"ORPHA:275555"},{"id":"PD-Preeclampsia-B_T2","span":{"begin":212,"end":224},"obj":"ORPHA:275555"},{"id":"PD-Preeclampsia-B_T3","span":{"begin":235,"end":269},"obj":"ORPHA:275555"},{"id":"PD-Preeclampsia-B_T4","span":{"begin":350,"end":370},"obj":"ORPHA:275555"},{"id":"PD-Preeclampsia-B_T5","span":{"begin":1419,"end":1431},"obj":"ORPHA:275555"}],"namespaces":[{"prefix":"ORPHA","uri":"www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN\u0026Expert="}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}

{"project":"Preeclampsia-compare","denotations":[{"id":"PD-Preeclampsia-B_T1","span":{"begin":48,"end":60},"obj":"ORPHA:275555"},{"id":"PD-Preeclampsia-B_T2","span":{"begin":212,"end":224},"obj":"ORPHA:275555"},{"id":"PD-Preeclampsia-B_T3","span":{"begin":235,"end":269},"obj":"ORPHA:275555"},{"id":"PD-Preeclampsia-B_T4","span":{"begin":350,"end":370},"obj":"ORPHA:275555"},{"id":"PD-Preeclampsia-B_T5","span":{"begin":1419,"end":1431},"obj":"ORPHA:275555"}],"namespaces":[{"prefix":"ORPHA","uri":"www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN\u0026Expert="}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}

{"project":"UBERON-AE","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":94,"end":118},"obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":573,"end":597},"obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":1310,"end":1334},"obj":"http://purl.obolibrary.org/obo/UBERON_0018229"}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}

{"project":"preeclampsia_genes","denotations":[{"id":"PD-PreeclampsiaGenes-B_T1","span":{"begin":14,"end":29},"obj":"HGNC:AGT"},{"id":"PD-PreeclampsiaGenes-B_T2","span":{"begin":120,"end":135},"obj":"HGNC:AGT"},{"id":"PD-PreeclampsiaGenes-B_T3","span":{"begin":482,"end":497},"obj":"HGNC:AGT"}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}

{"project":"PubCasesHPO","denotations":[{"id":"TI1","span":{"begin":48,"end":60},"obj":"HP:0100602"},{"id":"AB1","span":{"begin":195,"end":207},"obj":"HP:0000822"},{"id":"AB2","span":{"begin":212,"end":224},"obj":"HP:0100602"},{"id":"AB3","span":{"begin":1419,"end":1431},"obj":"HP:0100602"}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}

{"project":"PubCasesORDO","denotations":[{"id":"TI1","span":{"begin":48,"end":60},"obj":"ORDO:275555"},{"id":"AB1","span":{"begin":212,"end":224},"obj":"ORDO:275555"},{"id":"AB2","span":{"begin":1419,"end":1431},"obj":"ORDO:275555"}],"namespaces":[{"prefix":"ORDO","uri":"http://www.orpha.net/ORDO/Orphanet_"}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}

{"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":94,"end":118},"obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":573,"end":597},"obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":1310,"end":1334},"obj":"http://purl.obolibrary.org/obo/UBERON_0018229"}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}

{"project":"GlyCosmos15-HP","denotations":[{"id":"T1","span":{"begin":195,"end":207},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0000822"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":48,"end":60},"obj":"Disease"},{"id":"T2","span":{"begin":185,"end":207},"obj":"Disease"},{"id":"T3","span":{"begin":212,"end":224},"obj":"Disease"},{"id":"T4","span":{"begin":235,"end":256},"obj":"Disease"},{"id":"T5","span":{"begin":1419,"end":1431},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0005081"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0001134"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0005081"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0005044"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0005081"}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":35,"end":42},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":363,"end":370},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":94,"end":118},"obj":"Body_part"},{"id":"T2","span":{"begin":573,"end":597},"obj":"Body_part"},{"id":"T3","span":{"begin":1310,"end":1334},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0018229"}],"text":"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system.\nAngiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency \u003e 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."}