Kidney , enzymes

The natural blood globulin, angiotensinogen, Is converted by the proteolytic kidney enzyme, renin, to the decapeptide angiotensin 1. This substance is not a pressor agent but is cleaved by plasma converting enzyme to the powerful vasoconstrictor angiotensin II, an octapeptide. 

Mutarotation of 0.3% solutions of the freshly dissolved sugars in 12 ml of 5 mM EDTA, pH 7.4 was followed. Significant differences in mutarotation rates (AK) in the presence and absence of 100 units of bovine kidney enzyme were expressed as the ratio AK/Ksp. Differences of less than 5% in these rate constants were not considered significant. Of the 18 sugars listed, nine have been tested previously as substrates for other mammalian mutarotases with essentially the same pattern as described here. The pattern of specificity indicates that a 3-point attachment of enzyme and substrate is necessary for catalysis of mutarotation. b Data from 72). 

Km of 19 mM is found in most other mammals (Figure 6). In the calf all three forms of the enzyme are found at different stages of development with a 5 mM type predominating in the embryo, and the 12 mM form being found in the newborn animal up to the age of about 6 months (87). Recently the situation in humans has been found to be unusual since the purified human kidney enzyme is the 12 mM type, whereas the liver enzyme has a Km of 19 mM (76). 

The ability of enzyme preparations from various animal tissues to catalyze transfer of the glutamyl unit from glutamine or glutathione to certain a-amino acids and peptides, first observed by Hanes et al. (38), has been examined in several laboratories (32, 35, 39-41). Enzymes of this type have been studied recently by Orlowski and Meister (in hog kidney) (32) and by Szewczuk and Baranowski (in beef kidney) (41)-Results with the hog kidney enzyme will be reviewed here the beef enzyme is quite similar in many respects, but it is not identical in physical properties. 

The reaction mixtures contained initially mouse kidney enzyme (0.5 mg), l- or D-amino acids (5 pmoles), D,L-amino acids (lOpmoles), MgCU (4 pmoles), and 2-amino-2-(hydrox-ymethyl)-l,3-propanediol-HCl buffer (33 pinoles pH 8.3) in a final volume of 0.2 ml 37° analysis hy procedure C. 

Kidney FDPase preparations resemble those obtained from liver in their sensitivity to inhibition by AMP (20, 43, 43, 63). The swine kidney enzyme was almost completely desensitized by exposure at 30° to 22%... 

At least two distinct FDPases are found in animal tissues, one in liver and kidney, and the other in white muscle. The liver and kidney enzymes show minor differences in amino acid composition and in their response to agents, such as pyridoxal phosphate (4%), but these differences may be the result of modification during isolation (see above). On the other hand, the muscle enzyme is distinctly different in immunological properties as well as in amino acid composition (63, 74). All of the mammalian FDPases are similar in having a molecular weight of approximately 135,000, and all are composed of four subunits the... 

Liu and co-workers treated the (V,N -bis(trimethylsilyl) derivatives of 104 with 2,3,5-tris-O-benzoyl-D-ribosyl bromide. Debenzoylation of the intermediate product afforded /J-D-ribofuranosyl-/V,/V -pentameth-yleneurea nucleoside 137, found to be a cytidine deaminase (CDA) inhibitor against mouse kidney enzyme (although less effective than the seven- or six-membered ring homologs) (81JMC662). 

Shales, Otto, Kidney Enzymes and Essential Hypertension, F. F. Nord, ed., Advances in... 

I. Gentzen, H.-G. Loffler, and F. Schneider, Aminoacylase from Aspergillus oryzae. Comparison with the pig kidney enzyme, Z. Naturforsch. 1980, 35c, 544-550. 

Table VI summarizes total GSH-Px activity toward LHP and 15-HPETE in tissues from rats fed on vitamin E and/or Se deficient diets. GSH-Px activity toward fatty acid hydroperoxides was reduced markedly in liver and lung under Se-deficient states whereas kidney enzyme levels were only marginally affected. It should be noted that these total enzyme activities were contributed by both Se-GSH-Px and non-Se GSH-Px in crude cytosols of Se supplemented animals. However, in Se-deficient...

Na+, K+-ATPase was inactivated by FSB A in the presence of Mg23-. Although Na+ and K+ are not essential for inactivation, they accelerate the inactivation rate. In the absence of Mg2+, the enzyme was not inactivated by FSB A even in the presence of both Na+ and K+. Sequence study on the FSBA-modified dog kidney enzyme revealed that one of the major labeled sites is a lysyl residue equivalent to Lys-725 of the torpedo enzyme. The simultaneous replacement of both Lys-712 and Lys-713 by Met of SR-ATPase (The two lysyl residues are equivalent to Lys-725 and Lys-726 of the torpedo Na+, K+-ATPase) did not change the Ca2+-transporting activity or the formation of phosphoenzyme intermediate,781 indicating that these lysyl residues are not essential for enzyme activity. 

The localization at the cellular and subcellular levels of the liver and kidney enzymes responsible for this reduction as well as the mechanism of action have been studied by Aymard et al. (69) the liver enzymic activity is localized mainly in the cytosol while the kidney enzymatic activity appears to be associated mainly with the cell membranes and nuclei. In both cases, the enzyme is thermolabile and its activity is enhanced by adding NADH. 

The kidney enzyme involved in the release of lysine from c-(y-glu-tamyl) lysine is not the e-acyllysinase found by Leclerc and Benoiton (84) to liberate lysine from e-formyllysine and c-acetyllysine. This was... 

Figure 4.10 Fits to kinetic data from [135] on the operation of citrate synthase from rat kidney. Data (flux as a function of substrate concentrations) were obtained from Figures 2, 3, 4, 5, 6, 7, and 9 of [135], Initial fluxes (p.mol of COASH (or CIT) synthesized per minute per ug of enzyme) measured at the substrate concentrations indicated are plotted in A, B, C, and D. For A, B, and D, the initial product (CIT and COASH) concentrations are zero. In C, flux was measured with COASH added in various concentrations to investigate the kinetics of product inhibition. E and F show fits to kinetic data on the reverse operation of kidney enzyme, with product concentrations indicated in the figure. All data were obtained at pH = 8.1 at 28 °C. Model fits in all cases are plotted as solid lines.

In spite of the large eflFects of or on the activity of lens aminopeptidase (and probably on the kidney enzyme as well), it is doubtful if they play any physiological role. The relative concentrations of Zn ", Mg and Mn " and the pH of the particular tissues in question are such as to preclude formation of any hybrid metalloenzymes in vivo. However, the fact that the activation does occur indicates its potential for occurring in vivo although it may not be brought about by Mg " or Mn2 ... 

Angiotensin 11 is an octapeptide derived from biologically inactive decapeptide angiotensin 1, which comes from angiotensino-gen through the cleavage by the kidney enzyme renin. It is... 

Thienamycin and its derivatives are exciting new antibiotics. Then-clinical use is limited, however, by their susceptibility to the kidney enzyme dehydropeptidase I. Reversible inhibition of this enzyme is provided by cilastatin [11]. The preparation of the S-cyclopropane portion [10] of cilastatin is achieved (16) by decomposition of ethyl diazoacetate in isobutylene [9] in the presence of the chiral copper catalyst R-7644. The product [10] is obtained in 92% e.e. and then further processed to cilastatin. Cilastatin is now marketed in combination with the thienamycin derivative imipenem as a very-broad-spectnim antibiotic. 

AT-Acetyl-D-glucosamine 6-phosphate is metabolized to the D-fructose ester more slowly (by preparations of kidney enzyme) than is D-glucosamine 6-phosphate/ Acetate inhibits the disappearance of AT-acetyl-n-glucos-amine 6-phosphate, but does not affect the disappearance of D-glucosamine 6-phosphate. A possible sequence of reactions for these transformations is as follows. ... 

Vitamin D is a fat soluble vitamin derived from cholesterol. In the human epidermis (skin), sunlight spontaneously oxidizes cholesterol to 7-dehydrocholesterol (Fig. 10.10a). The 7-dehydrocholesterol leaks into the blood where it isomerizes to cholecalciferol (vitamin D3, Fig. 10.10b and c). Cholecalciferol is enzymatically hydroxylated at C25 in the liver (25-cholecalciferol) and then passes to the kidney where another enzyme is activated by parathyroid hormone to hydroxylate it at Cl, forming calcitriol (Fig. lO.lOd). The kidney hydroxylase is sensitive to feedback inhibition. As the amount of calcitriol increases, it binds to the hydroxylase and alters the specificity of the kidney enzyme. Additional 25-cholecal-ciferol is hydroxylated to 24,25-dihydroxycholecalciferol (inactive calcitriol) instead of 1,25 dihydroxycholecalciferol (calcitriol). Other vitamin D derivatives that can be converted to calcitriol are obtained enzymatically from cholesterol in other vertebrates. The most common of these are vitamin D3 (lamisterol) and D2 (ergosterol) from cold-water fish such as cod, where their presence keeps membranes fluid at low body temperatures 10-20°C. 

In contrast, native liver and kidney enzymes exhibit maximal activ-ity38i,382 at neutral pH. Muscle and kidney enzymes at neutral pH require the metal ion-EDTA complex in the presence of free Mn2+ or Mg2+ ions for optimal activity.383,384... 

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