Expression of alkaline phosphatase loci in mammalian tissues

Abstract

[150] values for the intestinal enzyme varied among species to a much greater extent. This implies that in the liver/one/ kidney/placental (nonhuman) alkaline phosphatase the structures of the binding sites for these inhibitors have been highly conserved during mammalian evolution, but there has been much greater divergence of these structures in the evolution of intestinal alkaline phosphatases.At least three gene loci determine the various forms of alkaline phosphatase [ALPase; orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] that occur in human tissues: one coding for the placental form, at least one coding for the intestinal forms (adult and fetal), and at least one coding for the liver, bone, and kidney forms (1-4). These three classes of ALPase are sharply discriminated from one another by quantitative inhibition with L-phenylalanine (Phe), L-homoarginine (Har), and L-phenylalanylglycylglycine (PheGlyGly) as inhibitors and also by their thermostabilities (1,5,6). In a recent study using these criteria we compared the ALPases occurring in liver and in placenta from a series of mammals with those occurring in human liver and placenta (7). We found that in each of the animal species studied the liver and placental ALPases closely resembled each other and were also very similar to human liver ALPase, but they differed from human placental ALPase. We have now extended these studies to include bone, kidney, and intestinal ALPases from the various species. We have also extended the battery of inhibitors to include levamisole, which is a particularly potent inhibitor of liver, bone, and kidney ALPase (8, 9).We find that the liver, bone, kidney, and placental ALPases from the various species resemble each other and also human liver, bone, and kidney ALPases very closely, but they are sharply differentiated from the series of intestinal ALPases and from human placental ALPase. The results suggest that in these mammalian species there are two distinct forms of ALPase, a liver/bone/kidney/placental form and an intestinal form,

Primary structure of rat liver alkaline phosphatase deduced from its cDNA

“…The signal peptide for human intestinal ALP has 19 amino acid residues (Berger et al, 1987), whereas different values have been given for that of placental ALP, 17 (Kam et al, 1985) and 22 amino acid residues (Millan, 1986;Henthorn et al, 1986), though the reason for this discrepancy is not clear. The active site 'Asp-Ser-Ala' is well conserved at similar positions in human intestinal (Ser92), placental (Ser92) and liver-type (Ser93) ALPs as well as in rat liver ALP (Ser93), except that its third residue Ala is replaced by Gly in human placental ALP, probably considered to be one of data supporting the view that human placental ALP is a new evolutionary gene product (Goldstein et al, 1980). There is almost 90 % homology in the amino acid sequences of human intestinal and placental enzymes (Berger et al, 1987), the latter of which shows only 52 % homology to the human liver-type ALP .…”

“…At least three types of ALP (isoenzymes) are identified in human tissues: placental, intestinal and tissue-unspecific (referred to below as the liver-type) isoenzymes (Fishman, 1974). Available evidence, however, indicates that only two types of ALP are detectable in other animals, including the rat, where ALP in placenta is the liver-type isoenzyme (Goldstein et al, 1980). Although extensive studies have been done for enzymological and immunological characterization of these isoenzymes, surprisingly little is known about the detailed structure of ALPs.…”

A High-resolution, Fluorescence-based Method for Localization of Endogenous Alkaline Phosphatase Activity

“…None of the techniques yielded signal in the interspersed goblet cells (Figures 2A-2D, arrows), which lack alkaline phosphatase expression (McComb et al 1979;Wheater et al 1987;Harris 1990). Furthermore, none of the techniques produced staining in controls incubated with the intestinal-type specific alkaline phosphatase inhibitor l -phenylalanine (Figures 2I-2L) (Goldstein et al 1980). …”

Serum total and bone alkaline phosphatase levels and their correlation with serum minerals over the lifespan of sheep

“…These two isoforms represent the most relevant fraction of the total ALP activity, with an almost equal contribution to about 95% of this enzyme (Millán, 2006). Sheep present only the IALP and the TNSALP (Goldstein et al, 1980). BALP is one of the most sensitive markers of bone formation.…”

“…One of the most widely used biomarker of bone formation is a membranebound enzyme (ALP), its activity being the sum of four isoenzymes in humans: the intestinal ALP (IALP), the placental ALP, the germ cell ALP, and a tissue non-specific ALP (TNSALP) present in the liver, kidney and bone (Millán, 2006), each of them a product of different gene loci (Goldstein et al, 1980). Al-though the TNSALP derives from the same gene locus, BALP and the liver isoform differ in an organ-specific post-translational glycosylation, which allows their measurement by specific analytical biochemical immunoassays.…”