Haptoglobin acting as a Natural Inhibitor of Cathepsin B Activity


OBSERVATIONS in this laboratory on various homogenates and on tumour ascites fluid1,2 have suggested that a component in blood plasma acts as a powerful cathepsin inhibitor. In order to study this interesting finding, cathepsins B and D were first separated by gel filtration from the lysosomal pellet of calf liver homogenates and subsequently studied in their partially purified form. For the colorimetric assays edestin denatured with urea was used as a substrate in 0.1 molar acetate buffer at pH 5.0 according to Ottoson and Sylvén1. Both 0.004 molar cysteine and 0.05 EDTA must be added for maximum cathepsin B activity. Without their addition, or with added cysteine alone, extinction increments which were too small and erratic were obtained. By means of this system the cathepsin B and D activity changes could then be studied separately after the addition of small amounts of all the different available purified plasma protein fractions from normal human blood. One fraction only prepared from Cohn's fraction IV–b containing the haptoglobins exhibited a marked inhibitory effect on the cathepsin B activity. This inhibition was noted even at weak haptoglobin concentrations amounting to a quarter of the amount of enzyme. No inhibition was found on addition of other highly purified serum proteins such as transferrin, ceruloplasmin or α1-acid glycoprotein, nor by addition of pure sialic acid, which is a component of haptoglobin. The cathepsin D activity, however, remained totally uninfluenced by all of the plasma fractions.


  1. 1

    Ottoson, R., and Sylvén, B., Arch. Biochem. Biophys., 87, 41 (1960).

    CAS  Article  Google Scholar 

  2. 2

    Sylvén, B., Ottoson, R., and Révész, L., Brit. J. Cancer, 13, 551 (1959).

    Article  Google Scholar 

  3. 3

    Lineweaver, H. A., and Burk, D., J. Amer. Chem. Soc., 56, 658 (1934).

    CAS  Article  Google Scholar 

  4. 4

    Goldbarg, J. A., and Rutenburg, A. M., Cancer, 11, 283 (1958).

    CAS  Article  Google Scholar 

  5. 5

    Dobryszycka, W., and Lisowska, E., Biochim. Biophys. Acta, 121, 42 (1966).

    CAS  Article  Google Scholar 

  6. 6

    Laurell, C.-B., and Grönvall, C., in Adv. Clin. Chem. (edit. by Sobotka, H., and Stewart, C. P.), 5, 135 (Academic Press, New York, 1962).

    Google Scholar 

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SNELLMAN, O., SYLVÉN, B. Haptoglobin acting as a Natural Inhibitor of Cathepsin B Activity. Nature 216, 1033 (1967). https://doi.org/10.1038/2161033a0

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