Skip to main content
Gut logoLink to Gut
. 1983 Feb;24(2):136–142. doi: 10.1136/gut.24.2.136

Enzymes of collagen synthesis and type III procollagen aminopropeptide in the evaluation of D-penicillamine and medroxyprogesterone treatments of primary biliary cirrhosis.

E R Savolainen, T A Miettinen, P Pikkarainen, M P Salaspuro, K I Kivirikko
PMCID: PMC1420175  PMID: 6852623

Abstract

Changes in serum immunoreactive prolyl hydroxylase protein (IRPH), galactosylhydroxylysyl glucosyltransferase activity (GGT) and the aminoterminal propeptide of type III procollagen [Pro(III)-N-P] were studied in 21 patients with primary biliary cirrhosis during a follow-up period of up to three years. The patients received either D-penicillamine (600 mg/day), medroxyprogesterone acetate (5 mg/day), or a placebo, or no treatment after the D-penicillamine or medroxyprogesterone medication, each period lasting from nine to 15 months. The individual serum IRPH, GGT, and Pro(III)-N-P concentrations exceeded the upper normal limit in most patients. No significant changes were found in any of these three serum markers during any of the five different periods, nor was there any evidence for a decrease in the raised prolyl 4-hydroxylase activity in the hepatic biopsy specimens in response to any of the treatments. Galactosylhydroxylysyl glucosyltransferase activity decreased significantly in these specimens during medroxyprogesterone therapy, but the interpretation of this, the only positive change, remains unclear. The data suggest that D-penicillamine or medroxyprogesterone therapy may have no favourable effect on the increased hepatic collagen formation involved in primary biliary cirrhosis.

Full text

PDF
136

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anttinen H. Collagen glucosyltransferases activity in human serum. Clin Chim Acta. 1977 Jun 15;77(3):323–330. doi: 10.1016/0009-8981(77)90236-4. [DOI] [PubMed] [Google Scholar]
  2. Bolarin D. M., Savolainen E. R., Kivirikko K. I. Enzymes of collagen synthesis and type III procollagen amino-propeptide in serum from Nigerians with hepato-cellular carcinoma and other malignant diseases. Int J Cancer. 1982 Apr 15;29(4):401–405. doi: 10.1002/ijc.2910290407. [DOI] [PubMed] [Google Scholar]
  3. Bornstein P., Sage H. Structurally distinct collagen types. Annu Rev Biochem. 1980;49:957–1003. doi: 10.1146/annurev.bi.49.070180.004521. [DOI] [PubMed] [Google Scholar]
  4. Epstein O., De Villiers D., Jain S., Potter B. J., Thomas H. C., Sherlock S. Reduction of immune complexes and immunoglobulins induced by D-penicillamine in primary biliary cirrhosis. N Engl J Med. 1979 Feb 8;300(6):274–278. doi: 10.1056/NEJM197902083000602. [DOI] [PubMed] [Google Scholar]
  5. Epstein O., Jain S., Lee R. G., Cook D. G., Boss A. M., Scheuer P. J., Sherlock S. D-penicillamine treatment improves survival in primary biliary cirrhosis. Lancet. 1981 Jun 13;1(8233):1275–1277. doi: 10.1016/s0140-6736(81)92456-9. [DOI] [PubMed] [Google Scholar]
  6. Fleming C. R., Ludwig J., Dickson E. R. Asymptomatic primary biliary cirrhosis. Presentation, histology, and results with D-penicillamine. Mayo Clin Proc. 1978 Sep;53(9):587–593. [PubMed] [Google Scholar]
  7. Jain S., Scheuer P. J., Samourian S., McGee J. O. A controlled trial of D-penicillamine therapy in primary biliary cirrhosis. Lancet. 1977 Apr 16;1(8016):831–834. doi: 10.1016/s0140-6736(77)92778-7. [DOI] [PubMed] [Google Scholar]
  8. Kivirikko K. I., Myllylä R. Collagen glycosyltransferases. Int Rev Connect Tissue Res. 1979;8:23–72. doi: 10.1016/b978-0-12-363708-6.50008-4. [DOI] [PubMed] [Google Scholar]
  9. Kivirikko K. I., Myllylä R. Posttranslational enzymes in the biosynthesis of collagen: intracellular enzymes. Methods Enzymol. 1982;82(Pt A):245–304. doi: 10.1016/0076-6879(82)82067-3. [DOI] [PubMed] [Google Scholar]
  10. Kuutti-Savolainen E. R., Anttinen H., Miettinen T. A., Kivirikko K. I. Collagen biosynthesis enzymes in serum and hepatic tissue in liver disease. II. Galactosylhydroxylysyl glucosyltransferase. Eur J Clin Invest. 1979 Feb;9(1):97–101. doi: 10.1111/j.1365-2362.1979.tb01673.x. [DOI] [PubMed] [Google Scholar]
  11. Kuutti-Savolainen E. R. Enzymes of collagen biosynthesis in skin and serum and dermatological diseases. II. Serum enzymes. Clin Chim Acta. 1979 Aug 15;96(1-2):53–58. doi: 10.1016/0009-8981(79)90051-2. [DOI] [PubMed] [Google Scholar]
  12. Kuutti-Savolainen E. R., Risteli J., Miettinen T. A., Kivirikko K. I. Collagen biosynthesis enzymes in serum and hepatic tissue in liver disease. I. Prolyl hydroxylase. Eur J Clin Invest. 1979 Feb;9(1):89–95. doi: 10.1111/j.1365-2362.1979.tb01672.x. [DOI] [PubMed] [Google Scholar]
  13. Kuutti E. R., Tuderman L., Kivirikko K. I. Human prolyl hydroxylase. Purification, partial characterization and preparation of antiserum to the enzyme. Eur J Biochem. 1975 Sep 1;57(1):181–188. doi: 10.1111/j.1432-1033.1975.tb02289.x. [DOI] [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Myllylä R., Risteli L., Kivirikko K. I. Assay of collagen-galactosyltransferase and collagen-glucosyltransferase activities and preliminary characterization of enzymic reactions with transferases from chick-embryo cartilage. Eur J Biochem. 1975 Apr 1;52(3):401–410. doi: 10.1111/j.1432-1033.1975.tb04008.x. [DOI] [PubMed] [Google Scholar]
  16. Myllylä R., Risteli L., Kivirikko K. I. Collagen glucosyltransferase. Partial purification and characterization of the enzyme from whole chick embryos and chick-embryo cartilage. Eur J Biochem. 1976 Jan 2;61(1):59–67. doi: 10.1111/j.1432-1033.1976.tb09997.x. [DOI] [PubMed] [Google Scholar]
  17. Nimni M. E. Mechanism of inhibition of collagen crosslinking by penicillamine. Proc R Soc Med. 1977;70 (Suppl 3):65–72. doi: 10.1177/00359157770700S322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Prockop D. J., Kivirikko K. I., Tuderman L., Guzman N. A. The biosynthesis of collagen and its disorders (first of two parts). N Engl J Med. 1979 Jul 5;301(1):13–23. doi: 10.1056/NEJM197907053010104. [DOI] [PubMed] [Google Scholar]
  19. Rohde H., Vargas L., Hahn E., Kalbfleisch H., Bruguera M., Timpl R. Radioimmunoassay for type III procollagen peptide and its application to human liver disease. Eur J Clin Invest. 1979 Dec;9(6):451–459. doi: 10.1111/j.1365-2362.1979.tb00912.x. [DOI] [PubMed] [Google Scholar]
  20. Salaspuro M. P., Sipponen P., Ikkala E., Kolho L., Makkonen H. M., Miettinen T. A., Räsänen J. A., Siurala M. Clinical correlations and significance of orceinpositivity in chronic active hepatitis and primary biliary cirrhosis. Ann Clin Res. 1976 Jun;8(3):206–215. [PubMed] [Google Scholar]
  21. Savolainen E. R., Kero M., Pihlajaniemi T., Kivirikko K. I. Deficiency of galactosylhydroxylysyl glucosyltransferase, an enzyme of collagen synthesis, in a family with dominant epidermolysis bullosa simplex. N Engl J Med. 1981 Jan 22;304(4):197–204. doi: 10.1056/NEJM198101223040403. [DOI] [PubMed] [Google Scholar]
  22. Sherlock S., Scheuer P. J. The presentation and diagnosis of 100 patients with primary biliary cirrhosis. N Engl J Med. 1973 Sep 27;289(13):674–678. doi: 10.1056/NEJM197309272891306. [DOI] [PubMed] [Google Scholar]
  23. Sotaniemi E. A., Hynnynen T., Ahlqvist J., Ahokas J. T., Puoskari U., Pelkonen I. Effects of medroxyprogesterone on the liver function and drug metabolism of patients with primary biliary cirrhosis and chronic active hepatitis. J Med. 1978;9(2):117–128. [PubMed] [Google Scholar]
  24. Tuderman L., Kuutti E. R., Kivirikko K. I. Radiommunoassay for human and chick prolyl hydroxylases. Eur J Biochem. 1975 Dec 15;60(2):399–405. doi: 10.1111/j.1432-1033.1975.tb21016.x. [DOI] [PubMed] [Google Scholar]
  25. Tuderman L., Risteli J., Miettinen T. A., Kivirikko K. I. Serum immunoreactive prolyl hydroxylase in liver disease. Eur J Clin Invest. 1977 Dec;7(6):537–541. doi: 10.1111/j.1365-2362.1977.tb01648.x. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES