Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A model has been constructed using computer graphics for human renin based on the sequence derived from that of the gene and the 3-dimensional structure defined at high resolution for other homologous aspartic proteinases. Human renin can adopt a 3-dimensional structure close to that of other aspartic proteinases, in which amino acids corresponding to intron-exon junctions in the gene are at surface regions in the 3-dimensional structure. As expected, the essential catalytic residues are retained and the nearby residue 304 is alanine as in the mouse sequence, supporting the idea that Asp 304 of other aspartic proteinases may contribute to the low pH of their optimal activity. There are interesting differences at subsite S3' which may contribute to the specificity of human renin. Certain residues at the surface of the enzyme adjacent to the active site cleft are unique to renins and may play a role in recognition and binding of angiotensinogen.
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PMID:Computer graphics modelling of human renin. Specificity, catalytic activity and intron-exon junctions. 643 79

Human placenta is surprisingly rich in post-proline dipeptidyl peptidase activity. Among various cell fractions, microsomes have the highest specific activity. A homogeneous enzyme preparation is obtained in a six-step purification procedure. The final preparation appears homogeneous upon dodecyl sulfate electrophoresis, but analytical isoelectric focussing reveals various active bands with isoelectric points in the range of pH 3-4. The enzyme is a glycoprotein containing about 30% carbohydrate. Treatment with neuraminidase lowers the isoelectric points but does not reduce the heterogeneity of the band pattern. The subunit molecular weight is 120000 as estimated by dodecyl sulfate electrophoresis, whereas Mr of the native enzyme is greater than 200000, as can be concluded from gel filtration experiments. The purified dipeptidyl peptidase cleaves various synthetic and natural peptides, including substance P, kentsin, casomorphin and a synthetic renin inhibitor. In general, the specificity of the placenta peptidase is similar to that of post-proline dipeptidyl peptidase from other sources. Phenylalanylprolyl-beta-naphthylamide (Km = 0.02 mM, V = 92 U/mg) is the best substrate among various synthetic peptide derivatives. Only peptides with a free N-terminal amino group and proline, hydroxyproline, or alanine in position 2 of the N-terminal sequence are cleaved. However, X-Pro-Pro-. . . structures, e.g. as in bradykinin, are not attacked. 1 mM bis-(4-nitrophenyl)phosphate or 1 mM diisopropylfluorophosphate completely inactivate the peptidase within 30 min at 30 degrees C (pH 8). The peptidase is also completely inhibited by 1 mM Zn2+ and by other heavy metals.
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PMID:Isolation and characterization of dipeptidyl peptidase IV from human placenta. 675 24

The biological effects of 1-Sarcosine, 8-Threonine angiotensin II ([Sar1, Thr8]ANG II) on blood pressure, plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were investigated in six normal subjects on an unrestricted diet, and compared with those of 1-Sarcosine, 8-Isoleucine ANG II ([Sar1, Ile8]ANG II) and 1-Sarcosine, 8-Alanine ANG II ([Sar1, Ala8]ANG II). All three ANG II analogues (AIIA) showed agonistic pressor activity, that of [Sar1, Ile8]ANG II being greater than that of [Sar1, Thr8]ANG II or [Sar1, Ala8]ANG II. The antagonistic effect of [Sar1, Thr8]ANG II on blood pressure was less than [Sar1, I1e8]ANG II or [Sar1, Ala8]ANG II. Both [Sar1, Ile8]ANG II and [Sar1, Ala8]ANG II increased PAC and blocked the steroidogenic action of ANG II, while [Sar1, Thr8]ANG II showed little effect on PAC. All three AIIA caused similar suppression of PRA and showed no inhibitory effect on the decrease in PRA produced by ANG II. These results indicate that [Sar1, Thr8]ANG II is an AIIA with weak agonistic pressor action and that it has vascular selective properties. It is also suggested that ANG II receptors in a variety of target organs are heterogeneous.
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PMID:Effect of three angiotensin II antagonists, [Sar1, Thr8]-, [Sar1, Ile8]- and [Sar1, Ala8]angiotensin II on blood pressure and endocrine factors in normal subjects. 675 36

To study the hormonal and metabolic effects of prostacyclin (PGI2), 6 healthy women were infused iv with PGI2 (1, 2, 4, and 8 ng/kg/min. each for 20 min) dissolved in glycine buffer, or with glycine buffer only. Serial blood samples collected before, during and after the infusion were assayed for FSH, LH, prolactin, growth hormone, thyrotrophin, oestradiol, progesterone, testosterone, cortisol, thyroxine, triiodothyronine, renin, aldosterone, glucose, insulin, glucagon, cholesterol, high density lipoprotein-cholesterol, triglycerides, alkaline phosphatase, alanine and aspartate aminotransferases, bilirubin, sodium, potassium, chloride, calcium, inorganic phosphorous, creatinine and uric acid. PGI2 infusions were accompanied by increased levels of prolactin, growth hormone and cortisol, probably due to the stressful side-effects during PGI2 infusion. In addition, plasma renin activity, glucagon and blood glucose increased, whereas the other variables measured did not change. These PGI2-effects should be kept in mind, when PGI2 is used in clinical practice.
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PMID:Hormonal and metabolic effects of intravenous infusion of prostacyclin in healthy women. 675 11

Analogues of the carboxyl protease inhibitor, pepstatin, were synthesized from optically pure forms of N-(tert-butoxycarbonyl)-4-amino-3-hydroxy-6-methylheptanoic acid (Boc-Sta), and the inhibition of pepsin and renin was determined. In addition, the new amino acid (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic acid [AHPPA] was synthesized and the stereochemistry of the 3 and 4 positions established. The tripeptides isovaleryl-L-valyl-(3S,4S)-4-amino-3-hydroxy-6-methylheptanoyl-L-alanine isoamylamide [Iva-Val-(3S,4S)-Sta-Ala-NHiC5H11] and Iva-Val-(3S,4S)-AHPPA-Ala-NHiC5H11 were found to be potent inhibitors of pepsin with Ki = 1 x 10(-9) and 0.9 x 10(-9) M, respectively. Changing the chirality of the (3S)-hydroxy group to 3R or shortening the peptide chain diminished binding to pepsin over 100-fold. Three structural requirements necessary for potent inhibition of pepsin are proposed.
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PMID:Synthesis of analogues of the carboxyl protease inhibitor pepstatin. Effects of structure on inhibition of pepsin and renin. 676 29

The effects of Captopril on blood pressure and renal function were evaluated in ten patients with different degrees of hypertension. In seven, blood pressure was reduced after 7 weeks of therapy; in three it remained practically unchanged. No correlation was found between the standing plasma renin activity before treatment and the hypotensive response. Plasma renin activity increased significantly from the median value of 5.4 (range 1-16.7) to 9.5 (range 2.6-19.8) ng ml-1 h-1 (P less than 0.05) and urine aldosterone significantly fell from 13 (range 2.3-52.5) to 7.4 (range 1.6-14) microgram 24 h-1 (P less than 0.01) during therapy. Renal plasma flow decreased from 534 (range 300-616) to 471 (range 333-606) ml min-1, but the difference was not significant, and glomerular filtration rate fell significantly form 122 (range 64-143) to 88 (range 71-116) ml min-1 (P less than 0.05). No urinary excretion of alpha 2-macroglobulin was observed during Captopril. 24 h proteinuria, albumin and transferrin clearance, alanine-amino transferase, gammaglutamyl transferase and alpha glucosidase excretion rate and malate-dehydrogenase clearance remained unaltered throughout the treatment. This indicates that neither glomerular permeability nor renal tubular function were affected by the drug.
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PMID:Hypotensive and renal effects of captopril. 680 Aug 13

To study the secretion of adrenocortical steroids, the renin releasing test and the angiotensin II analog (1-Sar, 8-Ala-Angiotensin II) infusion test was performed on four subjects with primary aldosteronism. The plasma renin activities of these subjects in the preoperative state were rather low, without any response to the renin releasing test. Plasma aldosterone was, however, significantly high and showed a tendency to declineits value when the subject was in an upright position. In the preoperative state, all the subjects lacked any alterations in plasma renin activity throughout the angiotensin II analog infusion test. Though slight elevations were observed in the blood pressure of three subjects, there was no demonstrable change in plasma aldosterone. In the other subject, though blood pressure did not change, plasma aldosterone exhibited a remarkable rise as did progesterone, 11-deoxycorticosterone and corticosterone. From these data, it was suggested that in the latter subject the aldosterone secretion was sensitive to angiotensin in comparison with ACTH. Three weeks after the operation, it was observed that plasma aldosterone response decreased, while the response of plasma renin activity to the renin releasing test was normal. This is considered to be due to the diminished sensitivity of the glomerulosa of the nonadenomatous adrenal gland to angiotensin. The levels of 17 alpha-hydroxyprogesterone, 11-deoxycorticosterone and corticosterone were almost within the normal range in the pre- and postoperative state. The levels of plasma progesterone and 11-deoxycorticosterone, however, tended to be lower in the postoperative state compared with the preoperative state.
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PMID:[Corticoid secretion in primary aldosteronism. II. The renin releasing test and the angiotensin II analog infusion test (author's transl)]. 698 96

To evaluate the role of the renin-angiotensin system and sodium depletion in the hypotensive response to 1-sarcosine-8-alanine-angiotensin II (saralasin), 15 male patients with essential hypertension were studied on a diet containing 120 mEq of sodium and 100 mEq of potassium per day. After a 5-day control period, all subjects had a mild pressor response to the saralasin infusion (p less than 0.01). After 5 days of the diuretic metolazone (5 mg/day), eight of the 15 patients had a vasodepressor response; these responders had a significantly greater increase in plasma renin activity and angiotensin II concentrations than did the non-responders. Sodium deficit differed markedly (p less than 0.001) between the two groups (361 +/- 121 mEq (SD) vs 52 +/- 26 mEq sodium, respectively). The addition of spironolactone (400 mg/day) for 5 days resulted in saralasin responsiveness in all but two patients, both of whom had small sodium deficits. Thus, variability in the natriuretic response to diuretics may affect saralasin testing and limit its clinical utility.
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PMID:Angiotensin II, plasma renin and sodium depletion as determinants of blood pressure response to saralasin in essential hypertension. 698 3

Two angiotensin II analogues (AIIA), 1-sarcosine, 8-isoleucine angiotensin II ([Sar, Ile]-AII) and 1-sarcosine, 8-alanine angiotensin II ([Sar, Ala]-AII), were infused in six normal volunteers on high, regular and low sodium diets. The agonist and antagonist activities of these AIIA on blood pressure (BP), plasma aldosterone concentration (PAC), creatinine clearance and plasma renin activity were examined. Both AIIA had agonistic pressor activities in subjects on high and regular sodium diets, [Sar, Ile]-AII being more potent than [Sar, Ala]-AII. Both AIIA caused similar elevation of PAC in subjects on high and regular sodium diets, and an equally fall in PAC in subjects on a low sodium diet. Both AIIA strongly antagonized the rise in BP, the increase in PAC and the reduction of Ccr induced by AII administration in subjects on all three sodium diets. The results indicate that both AIIA can be used to examine the activity of the renin-angiotensin system in patients with hypertension, and they also suggest that AII interaction with its receptors differs in different target tissues.
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PMID:Effects of two angiotensin II analogues on blood pressure, plasma aldosterone concentration, plasma renin activity and creatinine clearance in normal subjects on different sodium intakes. 700 66

A porcine kidney microsomal metalloendopeptidase has been enriched 3900-fold. Gel filtration on a calibrated Toyo-Soda G-3000 SW column indicated an appropriate molecular weight for the endopeptidase of 88,000 +/- 2000. The purified enzyme is inhibited by a number of synthetic inhibitors of thermolysin. The endopeptidase hydrolyzes the succinyl (Suc)-containing fluorogenic peptide substrate Suc-Ala-Ala-Phe-(7-amino-4-methylcoumarin) at the Ala-Phe position with a Km of 2.9 X 10(-4) M. The endopeptidase also hydrolyzes a variety of peptides including corticotropin, substance P, angiotensin I and II, neurotensin, somatostatin, bradykinin, and the renin tetradecapeptide substrate. The endopeptidase hydrolyzes both [Leu]- and [Met]enkephalin at the Gly-Phe bond.
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PMID:Purification of a membrane-bound metalloendopeptidase from porcine kidney that degrades peptide hormones. 703 58


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