Leucine aminopeptidase enzymic properties

Proximal tubule cells in culture should have retained functional attributes such as (1) polar architecture and junctional assembly of epithelia and correct membrane distribution of enzymes and transport systems (2) vectorial transport of solutes and water, manifested by the formation of domes when cultured on solid supports [81] and the generation of transepithelial electrophysiological properties [82, 83] due to the expression of proximal tubule specific claudins 2- and 10 [84, 85] (3) cellular uptake of xenobiotics from either the apical or basolateral side, as observed in vivo and (4) expression of nephron segment-specific characteristics, i.e., distinct expression of differentiation markers, metabolic and transport properties, and hormone responsiveness. Such markers include the expression of the brush border enzymes alkaline phosphatase, leucine aminopeptidase, and y-glutamyl transferase [4, 86], In addition, proximal tubule cells should possess Na+,K+-ATPase activities, Na+-dependent glucose, and p-aminohippurate transport. Proximal tubule cells increase cAMP levels in response to parathyroid... 

This section will focus on the structure and properties of the two best characterized examples of aminopeptidases that contain dinuclear zinc centers, both of which happen to be leucine aminopeptidases the enzymes from bovine lens (blLAP) and the marine bacterium Aeromonas proteo-lytica (AAP). Despite the fact that they catalyze the same reaction with comparable efficiencies,... 

Leucine Aminopeptidase, Leucine aminopeptidase was named at a time when only a few authentic peptides were available for study. The ability of intestinal preparations to split peptides containing N-terminal leucine was shown by Linderstr0m-Lang in 1929, and the enzyme responsible was partially purified by Johnson el dJ in 1936. The purified enzyme requires a divalent cation, Mg++ or Mn++, for activity. The properties of this enzyme have been studied extensively by Smith and his collaborators. They have found that the corresponding activity in hog kidney can be purified more highly than the best preparations obtained from intestinal mucosa. The properties described below are for the hog kidney enzyme, but the corresponding enzymes from other sources appear to have similar properties. 

Cathepsins. Cathepsins are intracellular proteases of animal origin. The occurrence of several such enzymes has been demonstrated in various tissues, including spleen, pituitary gland, kidney, thymus, etc. It is obvious that there is no reason to anticipate that all cathepsins will have similar properties to each other or to any other proteases. Cathepsins have been designated by both Roman numerals and by letters. Some of these enzymes have been identified with enzymes purified independently, as cathepsin III with leucine aminopeptidase. Several are activated by sulfhydryl compounds, some by metals. The isolation of the various cathepsins and studies of their substrate specificities are subjects currently under investigation, but because of the lower concentration of enzyme in the source materials and the number of related enzymes present, this area of investigation has not reached the development of the study of digestive enzymes. 

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