Kidneys enzyme production

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). 

Huet, A.C., C. Charlier, S.A. Tittlemier, et al. 2006. Simultaneous determination of (fluoro)quinolone antibiotics in kidney, marine products, eggs, and muscle by enzyme-linked immunosorbent assay (ELISA). J. Agric. Food Chem. 54 2822-2827. 

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.

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. 

Kynurenine is hydroxylated to hydroxykynurenine by an enzyme (kynurenine-3-hydroxylase) found in rat liver mitochondria. The reaction requires NADPH and molecular oxygen. In the presence of pyridoxal phosphate, hydroxykynurenine is hydrolyzed by an enzyme (kynurenase) found in liver and kidney. The product of this reaction is 3-hydroxyanthranilic acid. The same enzyme catalyzes the cleavage of the side chain of kynurenine to yield alanine and anthranilic acid. Studies made with labeled 3-hydroxyanthranilic acid demonstrated its role as an intermediate of the biosynthesis of nicotinic acid. These studies established that the label of the carbon 3 of 3-hydroxyanthranilic acid is transferred to the a-carbon of quinolinic acid and is lost as C14O2 during the conversion of quinolinic to nicotinic acid. The details of the metabolic conversion of 3-hydroxyanthranilic acid to nicotinic acid are known. 

The volume of extracellular fluid is direcdy related to the Na" concentration which is closely controlled by the kidneys. Homeostatic control of Na" concentration depends on the hormone aldosterone. The kidney secretes a proteolytic enzyme, rennin, which is essential in the first of a series of reactions leading to aldosterone. In response to a decrease in plasma volume and Na" concentration, the secretion of rennin stimulates the production of aldosterone resulting in increased sodium retention and increased volume of extracellular fluid (51,55). 

Carbonic anhydrase is an enzyme that produces free hydrogen ions, which are then exchanged for sodium ions in the kidney tubules. Carbonic anhydrase inhibitors inhibit the action of the enzyme carbonic anhydrase This effect results in the excretion of sodium, potassium, bicarbonate, and water. Carbonic anhydrase inhibitors also decrease the production of aqueous humor in the eye, which in turn decreases intraocular pressure (IOP) (ie, the pressure within the eye). 

Copper is an essential trace element. It is required in the diet because it is the metal cofactor for a variety of enzymes (see Table 50—5). Copper accepts and donates electrons and is involved in reactions involving dismu-tation, hydroxylation, and oxygenation. However, excess copper can cause problems because it can oxidize proteins and hpids, bind to nucleic acids, and enhance the production of free radicals. It is thus important to have mechanisms that will maintain the amount of copper in the body within normal hmits. The body of the normal adult contains about 100 mg of copper, located mostly in bone, liver, kidney, and muscle. The daily intake of copper is about 2—A mg, with about 50% being absorbed in the stomach and upper small intestine and the remainder excreted in the feces. Copper is carried to the liver bound to albumin, taken up by liver cells, and part of it is excreted in the bile. Copper also leaves the liver attached to ceruloplasmin, which is synthesized in that organ. 

The adult male prostate contains abundant acid phosphatase which it secretes into the semen. The production of this enzyme is governed by the circulating levels of androgenic hormones. Castration or estrogen administration markedly reduces the prostatic urinary acid phosphatase of males. Other organs such as the liver, kidney, spleen, red cells and platelets also contain significant amounts of acid phosphatase. 

Although the kidneys are not considered endocrine glands per se, they are involved in hormone production. Erythropoietin is a peptide hormone that stimulates red blood cell production in bone marrow. Its primary source is the kidneys. Erythropoietin is secreted in response to renal hypoxia. Chronic renal disease may impair the secretion of erythropoietin, leading to development of anemia. The kidneys also produce enzymes. The enzyme renin is part of the renin-angiotensin-aldosterone system. As will be discussed, these substances play an important role in the regulation of plasma volume and therefore blood pressure. Other renal enzymes are needed for the conversion of vitamin D into its active form, 1,25-d i hyd ro xyv itamin D3, which is involved with calcium balance. 

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