Kinins IV pp 469-475 | Cite as

Kininase II of Human Seminal Fluid: Kinetics and Inhibition

  • Marc van Sande
  • Hugo Neels
  • Simon Scharpé
  • Barton Holmquist
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 198A)


The activity of kininase II in crude human sperm was measured continuously by measuring the hydrolysis of a blocked tripeptide 3-(2- furylacryloyl)-L- phenylalanyl-glycl-glycine (1 mmol/1). Mean seminal plasma activity was 335±6l U/g protein; the Km was 0.7 mmol/1; pH optimum was 8.8 in a 50 mmol/1 HEPES buffer and the chloride optimum was 300 mmol/1. This male genital tract enzyme is inhibited by several kininase II inhibitors. Captopril (SQ 14225) showed IC50 = 1.6 × 10−8 mol/1, with a competitive pattern (Ki = 7.3 × 10−9). 3-(Mercaptomethy1)-oxo- piperidineacetic acid showed the same kind of inhibition with an IC50 = 1.8 × 10−6 mol/1 (Ki = 6.8 × 10−7 mol/1). Enalapril diacid was the most potent inhibitor and had an IC50 of 4.1 × 10−9 mol/1 and showed a mixed competitive and non-competitive inhibition (Ki = 10−9 mol/Ki’ = 9.5 × 10−10 mol/1). These in vitro inhibition data suggest that, in vivo, such drugs may effect the function of kininase II in the male reproductive system. The observed 50% inhibition constants are comparable to those observed in lung enzyme suggesting similar kinetic properties.


Angiotensin Converting Enzyme Sperm Motility Seminal Plasma Seminal Fluid Rabbit Lung 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    M. A. Hollinger, Serum angiotensin-converting enzyme. Status report on its diagnostic significance in pulmonary disease, Chest, 83: 589–590, (1983).CrossRefGoogle Scholar
  2. 2.
    D. Depierre, J. P. Bargetzi, and M. Roth, Dipeptidyl carboxypeptidase from human seminal sperm, Biochim. Biophys. Acta, 523: 469–476, (1978).PubMedCrossRefGoogle Scholar
  3. 3.
    S. Kaneko, & C. Moriwaki, Studies on dipeptidyl carboxypeptddase in the male reproductive organs; its biological and pathological status J. Pharm. Dyn., 4: 175–183, (1981).CrossRefGoogle Scholar
  4. 4.
    S. Kaneko, & C. Moriwaki, Effects of kinins and dipeptidyl carboxypeptidase on the motility of highly washed human sperm, J. Pharm. Dyn., 4: 443–450, (1981).CrossRefGoogle Scholar
  5. 5.
    M. Horiuchi, K. I. Fukumura, T. Terashima, & T. Iso, Method for determination of angiotensin-converting enzyme activity in blood and tissue by high performance liquid chromatography, J. Chromatogr. 233: 123–130, (1982).PubMedCrossRefGoogle Scholar
  6. 6.
    M. A. Ondetti, B. Rubin, & D. W. Cushman, Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents, Science, 166: 441–444, (1977).CrossRefGoogle Scholar
  7. 7.
    S. Klutcho, M. L. Hoefle, R. D. Smith, et al., Synthhsis and angio-tensin-converting enzyme inhibitory activity of 3-(mercaptomethyl)- 2-oxo-l-pyrrolidineacetic acids and 3-(mercaptomethyl)-2-oxo-l- piperidineacetic acids, J. Med. Chem., 24: 104–109, (1980).CrossRefGoogle Scholar
  8. 8.
    A. A. Patchett, E. Harris, E. W. Tristram, et al., A new class of angiotensin-converting enzyme inhibitors, Nature, 288: 280–283, (1980).PubMedCrossRefGoogle Scholar
  9. 9.
    R. J. Klauser, C. J. G. Robinson, D. V. Marinkovic, & E. G. Erdos, Inhibition of human peptidyl dipeptidase (angiotensin-I converting enzyme: kininase II) by human serum albumin and its fragments, Hypertension, 1: 281–286, (1979).PubMedCrossRefGoogle Scholar
  10. 10.
    B. Holmquist, P. Biinning, & J. F. Riordan, A continuous spectrophotometry assay for angiotensin converting enzyme, Anal. Biochem., 95: 540–548, (1979).PubMedCrossRefGoogle Scholar
  11. 11.
    R. Eisenthal, & A. Cornish-Bowden, The direct linear plot. A new graphical procedure for estimating enzyme kinetic parameters, Biochem. J., 139: 715–720, (1974).PubMedGoogle Scholar
  12. 12.
    G. L. Atkins, & I. A. Nimmo, Current trends in the estimation of Michaelis-Menten parameters, Anal. Biochem., 104: 1–9, (1980).PubMedCrossRefGoogle Scholar
  13. 13.
    A. Cornish-Bowden, Principles of enzyme kinetics. Inhibitors and activators, Butterworths, London, p. 52, (1976).Google Scholar
  14. 14.
    R. B. Loftfield, & E. A. Eigner, Molecular order of participation of inhibitors (or activators) in biological systems, Science, 164: 305–308, (1969).PubMedCrossRefGoogle Scholar
  15. 15.
    H. M. Neels, S. L. Scharpi, M. E. van Sande, & G. A. Fonteyne, Single-reagent micro centrifugal assay for antiotensin converting enzyme, Clin. Chem., 30: 163–164, (1984).PubMedGoogle Scholar
  16. 16.
    D. W. Cushman, & H. S. Cheung, Concentrations of angiotensin converting enzyme in tissues of the rat, Biochim. Biophys. Acta, 250: 261–265, (1971).PubMedCrossRefGoogle Scholar
  17. 17.
    H. M. Neels, S. L. Scharpe, G. A. Fonteyne, et al., Fluorometric assay for angiotensin converting enzyme in human serum by centrifugal analysis, Clin. Chim. Acta, 141: 281–286, (1984).PubMedCrossRefGoogle Scholar
  18. 18.
    H. M. Neels, S. L. Scharpe, M. E. Van Sande, et al., Improved micro-method for assay of serum angiotensin converting enzyme, Clin. Chem., 28: 1352–1355, (1982).PubMedGoogle Scholar
  19. 19.
    S. Ronca-Testoni, Direct spectrophotometric assay for angiotensin converting enzyme in serum, Clin. Chem., 29: 1093–1096, (1983).PubMedGoogle Scholar
  20. 20.
    D. W. Cushman, H. S. Cheung, E. F. Sabo, & M. A. Ondetti, Design of potent competitive inhibitors of angiotensin converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl aminoacids, Biochem., 16: 5484–5491, (1977).CrossRefGoogle Scholar
  21. 21.
    H. Gravas, J. Biollaz, B. Waeber, et al., Effects of the oral angiotensin converting enzyme inhibitor MK-421 in human hypertension, Clin. Sci., 6: 281s–283s, (1981).Google Scholar
  22. 22.
    H. Sato, Components of kallikrein kinin system and treatment of male infertility, Keio J. Med., 29: 19–38, (1980).PubMedCrossRefGoogle Scholar
  23. 23.
    C. Gronhagen-Riska, & F. Fyhrquist, Purification of human lung angiotensin converting snzyme, Scand. J. Clin. Lab. Invest., 40: 711–719, (1980).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Marc van Sande
    • 1
  • Hugo Neels
    • 1
  • Simon Scharpé
    • 1
  • Barton Holmquist
    • 2
  1. 1.Faculty of MedicineUniversity of AntwerpWilrijkBelgium
  2. 2.Center for Biochemical and Biophysical Sciences and MedicineHarvard Medical SchoolBostonUSA

Personalised recommendations