Alternate Substrate (Product) Interactions

2018 ◽  
pp. 259-266
Author(s):  
N. S. Punekar
Keyword(s):  
Alternate Substrate

scholarly journals Localization of the novel angiotensin peptide, angiotensin-(1-12), in heart and kidney of hypertensive and normotensive rats

2008 ◽  
Vol 294 (6) ◽  
pp. H2614-H2618 ◽  
Author(s):  
Jewell A. Jessup ◽  
Aaron J. Trask ◽  
Mark C. Chappell ◽  
Sayaka Nagata ◽  
Johji Kato ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Renal Tubules ◽  
Uptake Mechanism ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Angiotensin Peptide ◽  
Wistar Kyoto ◽  
Renal Tubular ◽  
Alternate Substrate ◽  
First Time

A low expression of angiotensinogen in the heart has been construed as indicating a circulating uptake mechanism to explain the local effects of angiotensin II on tissues. The recent identification of angiotensin-(1-12) in an array of rat organs suggests this propeptide may be an alternate substrate for local angiotensin production. To test this hypothesis, tissues from 11-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats ( n = 14) were stained with purified antibodies directed to the COOH terminus of angiotensin-(1-12). Robust angiotensin-(1-12) staining was predominantly found in ventricular myocytes with less staining found in the medial layer of intracoronary arteries and vascular endothelium. In addition, angiotensin-(1-12) immunoreactivity was present in the proximal, distal, and collecting renal tubules within the deep cortical and outer medullary zones in both strains. Preadsorption of the antibody with angiotensin-(1-12) abolished staining in both tissues. Corresponding tissue measurements by radioimmunoassay showed 47% higher levels of angiotensin-(1-12) in the heart of SHR compared with WKY rats ( P < 0.05). In contrast, renal angiotensin-(1-12) levels were 16.5% lower in SHR compared with the WKY rats ( P < 0.05). This study shows for first time the localization of angiotensin-(1-12) in both cardiac myocytes and renal tubular components of WKY and SHR. In addition, we show that increased cardiac angiotensin-(1-12) concentrations in SHR is associated with a small, but statistically significant, reduction in renal angiotensin-(1-12) levels.

scholarly journals Effect of incorporation of cidofovir into DNA by human cytomegalovirus DNA polymerase on DNA elongation.

1997 ◽  
Vol 41 (3) ◽  
pp. 594-599 ◽  
Author(s):  
X Xiong ◽  
J L Smith ◽  
M S Chen
Keyword(s):  
Dna Synthesis ◽  
Dna Polymerase ◽  
Human Cytomegalovirus ◽  
Chain Elongation ◽  
Exonuclease Activity ◽  
Dna Chain ◽  
Alternate Substrate

Cidofovir (CDV) (HPMPC) has potent in vitro and in vivo activity against human cytomegalovirus (HCMV), CDV diphosphate (CDVpp), the putative antiviral metabolite of CDV, is an inhibitor and an alternate substrate of HCMV DNA polymerase. CDV is incorporated with the correct complementation to dGMP in the template, and the incorporated CDV at the primer end is not excised by the 3'-to-5' exonuclease activity of HCMV DNA polymerase. The incorporation of a CDV molecule causes a decrease in the rate of DNA elongation for the addition of the second natural nucleotide from the singly incorporated CDV molecule. The reduction in the rate of DNA (36-mer) synthesis from an 18-mer by one incorporated CDV is 31% that of the control. However, the fidelity of HCMV DNA polymerase is maintained for the addition of the nucleotides following a single incorporated CDV molecule. The rate of DNA synthesis by HCMV DNA polymerase is drastically decreased after the incorporation of two consecutive CDV molecules; the incorporation of a third consecutive CDV molecule is not detectable. Incorporation of two CDV molecules separated by either one or two deoxynucleoside monophosphates (dAMP, dGMP, or dTMP) also drastically decreases the rate of DNA chain elongation by HCMV DNA polymerase. The rate of DNA synthesis decreases by 90% when a template which contains one internally incorporated CDV molecule is used. The inhibition by CDVpp of DNA synthesis by HCMV DNA polymerase and the inability of HCMV DNA polymerase to excise incorporated CDV from DNA may account for the potent and long-lasting anti-CMV activity of CDV.

Role of cyclic GMP in cholinergic activation of Na-K pump in duck salt gland

1981 ◽  
Vol 240 (5) ◽  
pp. C207-C214 ◽  
Author(s):  
D. J. Stewart ◽  
A. K. Sen
Keyword(s):  
Sodium Pump ◽  
Intact Cell ◽  
Salt Gland ◽  
Ringer Solution ◽  
Direct Role ◽  
External Site ◽  
Alternate Substrate ◽  
Hydrolysis Of ◽  
Pnpp Hydrolysis

Na-K-ATPase will hydrolyze an alternate substrate, p-nitrophenylphosphate (pNPP). The hydrolysis is ouabain sensitive and occurs at an external site on the cell membrane, thereby allowing measurement of Na-K-ATPase activity in the intact cell. pNPP hydrolysis was monitored in salt gland slices incubated in a bicarbonate-buffered Ringer solution. Methacholine-stimulated pNPP hydrolysis was inhibited by either atropine or ouabain. The hydrolysis was also dependent on the presence of calcium and sodium in the Ringer solution. cGMP stimulated ouabain-sensitive pNPP hydrolysis at concentrations from 10(-8) M to 10(-4) M with an optimum at 10(-5) M. cAMP did not produce a significant activation of pNPP hydrolysis. The effect of cGMP ws not dependent on either sodium or calcium in the Ringer solution and was not inhibited by atropine. Hydrolysis of pNPP promoted by either methacholine or cGMP occurred under conditions where no net influx of Na+ into the cells could occur. Sodium-pump activation during cholinergic stimulation, therefore, does not depend on an elevation of cell sodium but must occur by another mechanism. cGMP appears to play a direct role in that mechanism.

scholarly journals Unique subunit packing in mycobacterial nanoRNase leads to alternate substrate recognitions in DHH phosphodiesterases

2014 ◽  
Vol 42 (12) ◽  
pp. 7894-7910 ◽  
Author(s):  
Rajpal Srivastav ◽  
Dilip Kumar ◽  
Amit Grover ◽  
Ajit Singh ◽  
Babu A. Manjasetty ◽  
...  
Keyword(s):  
Alternate Substrate

Meanings of Ki for conventional and alternate-substrate inhibitors

1981 ◽  
Vol 30 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Thomas Spector ◽  
W.Wallace Cleland
Keyword(s):  
Alternate Substrate

Studies on thiaminase I activity in ruminant faeces and rumen bacteria

1985 ◽  
Vol 104 (3) ◽  
pp. 637-642 ◽  
Author(s):  
J. W. Boyd
Keyword(s):  
Radioactive Isotope ◽  
Colorimetric Method ◽  
Kinetic Studies ◽  
Rumen Bacteria ◽  
Michaelis Constant ◽  
Thiaminase I ◽  
Alternate Substrate ◽  
Reaction Constants ◽  
Analytical Variation ◽  
Substrate Concentrations

SummaryKinetic studies of thiaminase I in extracts of ruminant faeces showed that the affinity for one substrate varied with the concentration of the other substrate in the manner of a two-step transfer mechanism. When the alternate substrate concentration was optimal, the apparent Michaelis constant (Km) for thiamine was 176 μΜ and the apparent Km for aniline was 3·19 mΜ. It is recommended that in routine thiaminase assays, the thiamine and aniline concentrations should be at least 1·5 and 25 mΜ, respectively. When non-saturating concentrations of thiamine are used in thiaminase assays the results should be reported as unimolecular reaction constants since the enzyme activity can be calculated only if suitable Km data have been determined.Improved radioactive and colorimetric thiaminase assays with saturating substrate concentrations gave similar results. The analytical variation of the colorimetric method was rather high but this method may be useful for laboratories which lack radioactive isotope facilities.Thiaminase assays were performed on cultures of 14 species of rumen bacteria. Only Megasphaera elsdenii had thiaminase activity and its cosubstrate specificity was different from the rumen thiaminase associated with cerebrocortical necrosis in ruminants. It was concluded that the source of rumen thiaminase in that disease has yet to be identified.

Design of alternate substrate inhibitors of serine proteases. Synergistic use of alkyl substitution to impede enzyme-catalyzed deacylation

1987 ◽  
Vol 30 (4) ◽  
pp. 589-591 ◽  
Author(s):  
Allen Krantz ◽  
Robin W. Spencer ◽  
Tim F. Tam ◽  
Everton Thomas ◽  
Leslie J. Copp
Keyword(s):  
Serine Proteases ◽  
Alkyl Substitution ◽  
Alternate Substrate
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