Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptidyldipeptide hydrolase [angiotensin I-converting enzyme, EC 3.4.15.1] was inhibited by inorganic and organic phosphorus compounds tested, except for beta-glycerophosphate, 5'-AMP, and 5'-ADP, at the reagent concentrations used. Orthophosphate and pyrophosphate nonspecifically inhibited the enzyme activity. The enzyme was also inhibited specifically by carboxylates. The degree of inhibition by aliphatic monocarboxylates increased in proportion to their chain length up to C14. Aromatic and omega-phenylalkylcarboxylates also inhibited the enzyme activity. The enzyme was noncompetitively inhibited by acetate, 3-phenylpropionate and laurate. The Ki's for acetate, 3-phenylpropionate, and laurate were 60, 3.3, and 2.5 mM, respectively.
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PMID:Some enzymatic properties of peptidyl dipeptide hydrolase (angiotensin I-converting enzyme). 19 38

Experiments with rabbit platelets in vitro revealed differences in the effect of the aggregation inducers (ADP and thrombin) and the aggregation inhibitor cyclic AMP on the activity of the enzymes of pentosephosphate pathway of glucose oxidation. ADP and thrombin decrease significantly the activity of glucoso-6-phosphate dehydrogenase (G-6-PDH) and riboso-5-phosphate-metabolizing enzymes (R-5-PME) in platelets during aggregation, whereas cyclic AMP produces no appreciable effect on the G-6-PDH activity, but increases significantly the R-5-PME activity. ADP decreases and cyclic AMP raises substantially the activity of R-5-PME. The differences were also revealed in the effects produced by cyclic AMP and cyclic GMP on the enzymes of pentosephosphate pathway of glucose oxidation. Unlike cyclic AMP, cyclic GMP decreased significantly the activity of G-6-PDH. The activity of R-5-PME and cyclic GMP transketolase was more pronounced than that of cyclic AMP. Like cyclic AMP, cyclic GMP differs from ADP and thrombin in the action produced on the enzymes of pentosephosphate pathway of glucose oxidation.
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PMID:[Effect of aggregation inducers and inhibitors on the pentosephosphate pathway enzymes of glucose conversion in the thrombocytes]. 22 Dec 44

Isolated fat cells from rat brown adipose tissue in vitro respond to insulin with an increase of pyruvate dehydrogenase (EC 1.2.4.1) activity due to conversion of the inactive form of the enzyme (PDHb) to the active form (PDHa). Like in white adipocytes this effect depends on the presence of glucose or 2-deoxyglucose in the medium. The interrelationship between the steady state of the PDH-system and the phosphorylation state of the adenine nucleotides was studied in white adipose tissue. While insulin in the presence of 2-deoxyglucose caused a large fall of the tissue ATP/ADP ratio which could explain the increase of PDHa activity, the ATP/ADP ratio remained unchanged during incubations with insulin and glucose. Thus it appears that other factors than the ATP/ADP ratio are involved in the regulation of PDH activity by insulin the nature of which remains to be elucidated.
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PMID:Activation of pyruvate dehydrogenase by insulin in isolated brown fat cells. 45 31

The effect of various antihypertensive medications on platelet function is of increasing interest. Conflicting effects of captopril on platelet function are reported and the impact of angiotensin converting enzyme (ACE) inhibitors not containing a sulfhydryl group such as enalapril, lisinopril, and quinapril on platelet function remains unstudied. Therefore, the aim of the present study was to examine the effect of antihypertensive treatment with quinapril, a novel ACE inhibitor not containing a sulfhydryl group, on platelet function. Ten white men (age range of 32-61 years) with untreated mild-to-moderate essential hypertension (supine diastolic blood pressure greater than 95 mm Hg) were treated with 4 weeks each of placebo and quinapril in a double-blind, randomized, crossover design. Quinapril (20 mg twice a day) significantly lowered systolic (p less than 0.01) and diastolic blood pressure (p less than 0.01) without any significant effect on heart rate or plasma catecholamines. No significant change was noted for in vitro platelet aggregation induced by epinephrine, ADP, or collagen. Plasma concentrations of the platelet release factors beta-thromboglobulin and platelet factor 4 did not change, nor did the platelet content of norepinephrine, platelet weight (mg/10 ml of blood), circulating platelet count, or platelet size. Thus, as assessed by a broad spectrum of platelet parameters, we found that antihypertensive treatment with quinapril has no significant effect on platelet function in patients with mild-to-moderate essential hypertension. These "platelet-neutral" properties of quinapril suggest that quinapril, both from a thromboembolic and a hemostatic point of view, may be a rather safe agent for treatment of hypertension.
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PMID:Platelet function during antihypertensive treatment with quinapril, a novel angiotensin converting enzyme inhibitor. 170 46

We have studied the acute and chronic effects of an ACE inhibitor (captopril) on platelet function and the renin-angiotensin system in patients with congestive heart failure. Plasma concentrations of angiotensin II fell significantly after a single dose of captopril (25 mg) and during long-term treatment with captopril (2 weeks, 75 mg/day). Plasma renin activity increased significantly after both the single and repeated doses. Captopril did not affect ADP-induced platelet aggregation or concentrations. It seems unlikely that circulating angiotensin II affects ADP-induced platelet aggregation in patients with congestive heart failure.
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PMID:A lack of effect of captopril on platelet aggregation in patients with congestive heart failure. 178 76

The effect of severe insulin-induced hypoglycemia on the activity of the pyruvate dehydrogenase enzyme complex (PDHC) was investigated in homogenates of frozen rat cerebral cortex during burst suppression EEG, after 10, 30, and 60 min of isoelectric EEG, and after 30 and 180 min and 24 h of recovery following 30 min of hypoglycemic coma. Changes in PDHC activity were correlated to levels of labile organic phosphates and glycolytic metabolites. In cortex from control animals, the rate of [1-14C]pyruvate decarboxylation was 7.1 +/- 1.3 U/mg of protein, or 35% of the total PDHC activity. The activity was unchanged during burst suppression EEG whereas the active fraction increased to 81-87% during hypoglycemic coma. Thirty minutes after glucose-induced recovery, the PDHC activity had decreased by 33% compared to control levels, and remained significantly depressed after 3 h of recovery. This decrease in activity was not due to a decrease in the total PDHC activity. At 24 h of recovery, PDHC activity had returned to control levels. We conclude that the activation of PDHC during hypoglycemic coma is probably the result of an increased PDH phosphatase activity following depolarization and calcium influx, and allosteric inhibition of PDH kinase due to increased ADP/ATP ratio. The depression of PDHC activity following hypoglycemic coma is probably due to an increased phosphorylation of the enzyme, as a consequence of an imbalance between PDH phosphatase and kinase activities. Since some reduction of the ATP/ADP ratio persisted and since the lactate/pyruvate ratio had normalized by 3 h of recovery, the depression of PDHC most likely reflects a decrease in PDH phosphatase activity, probably due to a decrease in intramitochondrial Ca2+.
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PMID:Changes in pyruvate dehydrogenase complex activity during and following severe insulin-induced hypoglycemia. 198 96

1. A new isolated perfused preparation is described that allows a direct comparison to be made of the responses of the perfused arterial and retrogradely perfused venous circulations of the rat superior mesenteric vascular bed. 2. In experiments comparing the responses of the intact arterially perfused mesentery and small intestine to those of the same preparation following removal of the intestine and division of the circulations, the increases in perfusion pressure produced by arginine-vasopressin (30 pmol) and noradrenaline (1 nmol) were retained by the arterial circulation and those induced by angiotensin II (30 pmol) by the venous circulation. Endothelin-1 (30 pmol) constricted both portions of the vasculature but the prolonged nature of its response was associated with only the venous vessels. 3. In the simultaneously perfused arterial and venous preparation arginine vasopressin (3-100 pmol) was a selective constrictor of the arterial circulation and angiotensin II (3-100 pmol) of the venous circulation. In addition, noradrenaline (0.3-10 nmol), 5-hydroxytryptamine (0.3-10 nmol) and KCl (1-60 micromol) were more active as constrictors of the arterial than the venous vessels, and U46619 (10-300 pmol) a more active constrictor of the venous than the arterial vessels. Endothelin-1 (3-100 pmol) constricted both the arterial and venous portions of the vasculature but was significantly longer acting as a venoconstrictor than an arterioconstrictor. 4. Angiotensin I (300 pmol) caused constrictions of the venous circulation which were dependent upon the presence of angiotensin converting enzyme for captopril (10 microM) abolished constrictions caused by angiotensin I but not by angiotensin II. 5. In preparations preconstricted by U46619 (0.3-3 microM), acetylcholine (0.01-100 nmol), bradykinin (0.001-nmol), sodium nitroprusside (0.01-lOnmol) or isoprenaline (1-l00pmol) produced dose-related dilatations of both the arterial and the venous vasculatures, whereas adenosine diphosphate (ADP, 0.01-lOOnmol) caused dose-dependent dilatations of the arterial circulation but principally constrictions of the venous circulation. The dilatations caused by acetylcholine and bradykinin in both portions of the circulation, and by ADP in the arterial circulation, were endothelium-dependent as they were inhibited by gossypol (3 microM), whereas dilatations to sodium nitroprusside were not. 6. This preparation allows the responses of the arteries and veins of a single perfused mesenteric bed to be compared. In addition, with this preparation it is possible to demonstrate that veins, as well as arteries, show significant endothelium-dependent relaxations. It is concluded that the venous portion of the vasculature is significantly involved in the responses of the intact circulation.
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PMID:Simultaneous perfusion of rat isolated superior mesenteric arterial and venous beds: comparison of their vasoconstrictor and vasodilator responses to agonists. 232 5

There are several indications that the oxygen supply to the myocardium is inadequate in chronic heart failure. This is due to an increased intramyocardial vascular resistance, elevated filling pressures, and a shortened diastolic perfusion time. In parallel, the myocardial oxygen demand is heightened due to elevated wall stress, heart rate and contractility. This imbalance between myocardial oxygen supply and demand might be the cause of the adaptive metabolic changes seen in severe chronic heart failure. We showed increased LDH 5, decreased LDH 1 and increased ADP/ATP-carrier concentration in the myocardium from patients with chronic heart failure. After ACE-inhibitor treatment in 33 patients with chronic heart failure, LDH 1 increased from 38.7 +/- 6.7% to 42.3 +/- 5.5% (P less than 0.005) paralleled by a decrease in LDH 5 from 20.8 +/- 7.0% to 15.8 +/- 4.7% (P less than 0.001). The ADP/ATP-carrier concentration also decreased significantly within the normal range. This shift in the LDH isoenzyme pattern and decrease in the ADP/ATP-concentration can be interpreted as an indication for an improvement of myocardial energy balance in chronic heart failure under ACE-inhibitor therapy. This might help interrupt the self-perpetuation of chronic heart failure which is partially caused by a progressive subendocardial perfusion deficit.
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PMID:The effect of ACE inhibition on myocardial energy metabolism. 236 54

Biochemical changes in the placenta were studied using alloxan-induced diabetes mellitus in the female rat. In comparison with a control group (n = 13) the placentas of the diabetic animals (n = 12) had significantly higher glucose, glycogen and protein levels. It was, however, shown that this supply of substrate was inadequately utilised for energy, as ATP/ADP quotient was lower and the ADP content was significantly higher. Metabolism still appeared to take place under aerobic conditions, as evidenced by the unchanged lactate levels. In terms of the protein content of the placentas, the activity of the enzymes we investigated (GOT, GPT, LDH, G-6-PDH, MDH, ICDH) was lowered by 25-44%. These results support the idea of global placental insufficiency in diabetics.
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PMID:Effects of alloxan-induced diabetes mellitus on the metabolism of the rat placenta. 395 50

Chronic hypertension is associated with impaired endothelial function [i.e., reduced synthesis/release of endothelium-derived relaxing factor (EDRF) and increased synthesis/release of endothelium-derived contracting factor (EDCF)] in both animals and humans. Although it is not known whether endothelial dysfunction is the consequence and/or an important pathogenetic cause of hypertension, the goal of effective antihypertensive therapy should include restoration of normal endothelial function as well. Because angiotensin I-converting enzyme (ACE) inhibitors are effectively used in the treatment of hypertension, the aim of the present study was to test whether in vivo treatment of spontaneously hypertensive rats (SHRs) with the ACE inhibitor cilazapril improves endothelial function in the isolated thoracic aorta of SHRs. Treatment of SHRs with cilazapril (10 mg/kg/day orally for 2 weeks) resulted in a significant decrease in blood pressure and normalization of endothelium-dependent relaxation evoked by acetylcholine (ACh) and adenosine diphosphate (ADP). However, cilazapril treatment had no significant effect on endothelium-dependent contractions evoked by 5-hydroxytryptamine (5-HT; serotonin) and prostaglandin F2 alpha (PGF2 alpha). In contrast, in vitro treatment of isolated thoracic aortas with indomethacin (10(-5) M) normalized endothelium-dependent relaxations to ACh and ADP as well as inhibited endothelium-dependent contractions to 5-HT and PGF2 alpha. These results suggest that the ACE inhibitor cilazapril increases the synthesis/release of EDRFs whereas indomethacin prevents the synthesis/release of cyclo-oxygenase-derived EDCFs in the endothelium of rat aorta. The exact mechanism of action of ACE inhibitors on endothelial dysfunction remains to be determined.
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PMID:Effect of cilazapril and indomethacin on endothelial dysfunction in the aortas of spontaneously hypertensive rats. 750 48


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