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Biochimica et biophysica acta1972; 268(2); 415-421; doi: 10.1016/0005-2744(72)90337-3

Imidazole: an inhibitor of L-phenylalanine-insensitive alkaline phosphatases of tissues other than intestine and placenta.

Abstract: 1. Alkaline phosphatases (orthophosphoric monoester phosphohydrolase, EC 3.1.3.1) from brain, kidney, liver, bone, lung and spleen, which are not very sensitive to l-phenylalanine, are strongly inhibited by imidazole, whereas the placental and intestinal enzymes, which are very sensitive to l-phenylalanine, are only slightly affected. This is a new possibility for distinguishing the alkaline phosphatase isoenzymes. 2. The inhibition is apparently of an uncompetitive type, suggesting that the inhibitor interacts with the ES complex to form an EIS complex. 3. Histidine acts upon all enzymes assayed in this study. Its inhibition is of a mixed type. 4. An interpretation, taking into account the role of the zinc atom(s) present in the active center, is offered.
Publication Date: 1972-05-12 PubMed ID: 5026309DOI: 10.1016/0005-2744(72)90337-3Google Scholar: Lookup
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  • Journal Article

Summary

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The research article investigates the impact of Imidazole on various tissues’ alkaline phosphatases and identifies a new way of distinguishing these isoenzymes based on their interactions with l-phenylalanine and Imidazole.

Understanding the Research

  • The study is focused on exploring alkaline phosphatases, enzymes commonly found in various human tissues like the brain, kidney, liver, bone, lung, and spleen.
  • Researchers have discovered that these enzymes, despite being relatively unaffected by l-phenylalanine, are strongly hindered by Imidazole. However, this effect varies for placental and intestinal enzymes, which are significantly affected by l-phenylalanine but only slightly influenced by Imidazole.
  • This discovery establishes a new method of differentiating between various isoenzymes of alkaline phosphatase by assessing their sensitivity to l-phenylalanine and Imidazole.

Inhibition Mechanism

  • The impact of Imidazole on the other tissues’ alkaline phosphatases is reportedly uncompetitive. This suggests that Imidazole forms a complex with the enzyme-substrate, known as the “ES complex,” producing a new “EIS complex,” which inhibits the enzyme’s function.
  • This uncompetitive inhibition provides a new dimension to understanding how substances can alter enzyme activity and contribute to biochemical research.

Role of Histidine

  • The research also tested the role of Histidine, a basic amino acid, on all enzymes included in the study. The inhibitory effect of Histidine was found to be of a mixed type, meaning it can bind to either the enzyme or the enzyme-substrate complex.
  • This nibbling upon varied inhibitory mechanisms provides an understanding of how different substances can influence the same enzymes in different ways.

Zinc Atoms

  • The research paper also proposes an interpretation about the role of zinc atoms present in the active center of enzymes.
  • While the details of this interpretation are not provided in the abstract, the role of metal ions like zinc in enzyme function is a crucial area of study in biochemistry, contributing to our understanding of how enzymes work on a molecular level.

Cite This Article

APA
Brunel C, Cathala G. (1972). Imidazole: an inhibitor of L-phenylalanine-insensitive alkaline phosphatases of tissues other than intestine and placenta. Biochim Biophys Acta, 268(2), 415-421. https://doi.org/10.1016/0005-2744(72)90337-3

Publication

ISSN: 0006-3002
NlmUniqueID: 0217513
Country: Netherlands
Language: English
Volume: 268
Issue: 2
Pages: 415-421

Researcher Affiliations

Brunel, C
    Cathala, G

      MeSH Terms

      • Alkaline Phosphatase / analysis
      • Alkaline Phosphatase / antagonists & inhibitors
      • Aminocaproates
      • Animals
      • Binding Sites
      • Bone and Bones / enzymology
      • Brain / enzymology
      • Cattle
      • Columbidae
      • Female
      • Guanidines
      • Histidine
      • Horses
      • Humans
      • Imidazoles
      • Intestines / enzymology
      • Kidney / enzymology
      • Liver / enzymology
      • Lung / enzymology
      • Organ Specificity
      • Phenylalanine
      • Placenta / enzymology
      • Pregnancy
      • Rabbits
      • Rats
      • Species Specificity
      • Spleen / enzymology
      • Zinc / analysis

      Citations

      This article has been cited 4 times.
      1. Jomori T, Matsuda K, Egami Y, Abe I, Takai A, Wakimoto T. Insights into phosphatase-activated chemical defense in a marine sponge holobiont. RSC Chem Biol 2021 Dec 2;2(6):1600-1607.
        doi: 10.1039/d1cb00163apubmed: 34977575google scholar: lookup
      2. Štefková K, Procházková J, Pacherník J. Alkaline phosphatase in stem cells. Stem Cells Int 2015;2015:628368.
        doi: 10.1155/2015/628368pubmed: 25767512google scholar: lookup
      3. Sterry W, Steigleder GK, Neumann G. Characterization of activity of alkaline phosphatase (AAP) in capillary endothelium of normal and psoriatic skin. Arch Dermatol Res 1980;267(2):131-9.
        doi: 10.1007/BF00569099pubmed: 7406528google scholar: lookup
      4. Felix R, Fleisch H. Properties of inorganic pyrophosphatase of pig scapula cartilage. Biochem J 1975 Apr;147(1):111-8.
        doi: 10.1042/bj1470111pubmed: 239696google scholar: lookup