Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1974 May;139(2):461–468. doi: 10.1042/bj1390461

Age-related variations in hydroxylation of lysine and proline in collagen

M J Barnes 1, B J Constable 1, L F Morton 1, P M Royce 1
PMCID: PMC1166303  PMID: 4447620

Abstract

The effect of age on the extent of hydroxylation of lysine and proline both generally and at certain specific sites in collagens from bone, skin and tendon was examined in the chick from the 14-day embryo to the 18-month-old adult. For all collagens there was a marked fall in the overall extent of hydroxylation of lysine with increasing age in both α1 and α2 chains, this fall occurring mostly in a relatively short period immediately after hatching. Hydroxylation of lysine declined to a constant value which, as expected, differed appreciably for each collagen and was considered to be characteristic of the collagen according to its tissue of origin. Hydroxylation of lysine in the N-terminal, non-helical telopeptide region of both α1 and α2 chains, which is important with regard to cross-linking, was relatively high in embryonic collagens. There was, however, a rapid loss of hydroxylation at these sites in skin collagen, occurring both during development of the embryo and in the period immediately after hatching. In contrast some hydroxylation at these sites persisted in bone and tendon collagens and, as judged by examination of peptide α1–CB1, appeared to reach a constant value in time of about 33% in bone and about 15% in tendon collagen. The actual extent of hydroxylation of lysine in the N-terminal telopeptides and the size of the changes in these values with age appeared to be unrelated to the corresponding whole-chain values, and it is suggested therefore that hydroxylation of telopeptidyl lysine may be under separate enzymic control. The increased hydroxylation of lysine in the embryo was accompanied by only minimal changes in proline hydroxylation, which was very slightly increased in embryonic bone and tendon collagens. Increased hydroxylation of proline in the embryo was, however, readily observed in peptide α1–CB2 from the helical region of tendon collagen. This hydroxylation was close to the theoretical maximum, in contrast with that observed in post-embryonic tendon, where hydroxylation was incomplete, as in rat tendon (Bornstein, 1967), only four on average, of the six susceptible proline residues being hydroxylated.

Full text

PDF
461

Selected References

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

  1. Anttinen H., Orava S., Ryhänen L., Kivirikko K. I. Assay of protocollagen lysyl hydroxylase activity in the skin of human subjects and changes in the activity with age. Clin Chim Acta. 1973 Aug 30;47(2):289–294. doi: 10.1016/0009-8981(73)90326-4. [DOI] [PubMed] [Google Scholar]
  2. Bailey A. J., Robins S. P. Embryonic skin collagen. Replacement of the type of aldimine crosslinks during the early growth period. FEBS Lett. 1972 Apr 1;21(3):330–334. doi: 10.1016/0014-5793(72)80195-9. [DOI] [PubMed] [Google Scholar]
  3. Barnes M. J., Constable B. J., Morton L. F., Kodicek E. Bone collagen metabolism in vitamin D deficiency. Biochem J. 1973 Jan;132(1):113–115. doi: 10.1042/bj1320113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barnes M. J., Constable B. J., Morton L. F., Kodicek E. Hydroxylysine in the N-terminal regions of the 1 - and 2 -chains of various collagens. Biochem J. 1971 Nov;125(2):433–437. doi: 10.1042/bj1250433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barnes M. J., Constable B. J., Morton L. F., Kodicek E. Hydroxylysine in the N-terminal telopeptides of skin collagen from chick embryo and newborn rat. Biochem J. 1971 Dec;125(3):925–928. doi: 10.1042/bj1250925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barnes M. J., Constable B. J., Morton L. F., Kodicek E. Studies in vivo on the biosynthesis of collagen and elastin in ascorbic acid-deficient guinea pigs. Evidence for the formation and degradation of a partially hydroxylated collagen. Biochem J. 1970 Sep;119(3):575–585. doi: 10.1042/bj1190575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Barnes M. J., Constable B. J., Morton L. F., Kodicek E. The influence of dietary calcium deficiency and parathyroidectomy on bone collagen structure. Biochim Biophys Acta. 1973 Dec 6;328(2):373–382. doi: 10.1016/0005-2795(73)90271-7. [DOI] [PubMed] [Google Scholar]
  8. Becker U., Timpl R. Cyanogen bromide peptides of the rabbit collagen a1-chain. FEBS Lett. 1972 Oct 15;27(1):85–88. doi: 10.1016/0014-5793(72)80415-0. [DOI] [PubMed] [Google Scholar]
  9. Bornstein P. Comparative sequence studies of rat skin and tendon collagen. I. Evidence for incomplete hydroxylation of individual prolyl residues in the normal proteins. Biochemistry. 1967 Oct;6(10):3082–3093. doi: 10.1021/bi00862a015. [DOI] [PubMed] [Google Scholar]
  10. Bornstein P., Piez K. A. The nature of the intramolecular cross-links in collagen. The separation and characterization of peptides from the cross-link region of rat skin collagen. Biochemistry. 1966 Nov;5(11):3460–3473. doi: 10.1021/bi00875a012. [DOI] [PubMed] [Google Scholar]
  11. Butler W. T. The structure of l-CB3, a cyanogen bromide fragment from the central portion of the l chain of rat collagen. The tryptic peptides from skin and dentin collagens. Biochem Biophys Res Commun. 1972 Sep 26;48(6):1540–1548. doi: 10.1016/0006-291x(72)90889-3. [DOI] [PubMed] [Google Scholar]
  12. Dixit S. N., Bensusan H. B. The isolation of crosslinked peptides of collagen involving alpha 1-CB6. Biochem Biophys Res Commun. 1973 May 1;52(1):1–8. doi: 10.1016/0006-291x(73)90945-5. [DOI] [PubMed] [Google Scholar]
  13. Eastoe J. E., Martens P., Thomas N. R. The amino-acid composition of human hard tissue collagens in osteogenesis imperfecta and dentinogenesis imperfecta. Calcif Tissue Res. 1973 May 9;12(2):91–100. doi: 10.1007/BF02013724. [DOI] [PubMed] [Google Scholar]
  14. Eyre D. R., Glimcher M. J. Analysis of a crosslinked peptide from calf bone collagen: evidence that hydroxylysyl glycoside participates in the crosslink. Biochem Biophys Res Commun. 1973 May 15;52(2):663–671. doi: 10.1016/0006-291x(73)90764-x. [DOI] [PubMed] [Google Scholar]
  15. Hulmes D. J., Miller A., Parry D. A., Piez K. A., Woodhead-Galloway J. Analysis of the primary structure of collagen for the origins of molecular packing. J Mol Biol. 1973 Sep 5;79(1):137–148. doi: 10.1016/0022-2836(73)90275-1. [DOI] [PubMed] [Google Scholar]
  16. Kang A. H., Bornstein P., Piez K. A. The amino acid sequence of peptides from the cross-linking region of rat skin collagen. Biochemistry. 1967 Mar;6(3):788–795. doi: 10.1021/bi00855a019. [DOI] [PubMed] [Google Scholar]
  17. Kang A. H., Igarashi S., Gross J. Characterization of the cyanogen bromide peptides from the alpha-2 chain of chick skin collagen. Biochemistry. 1969 Aug;8(8):3200–3204. doi: 10.1021/bi00836a011. [DOI] [PubMed] [Google Scholar]
  18. Kang A. H., Piez K. A., Gross J. Characterization of the alpha-chains of chick skin collagen and the nature of the NH2-terminal cross-link region. Biochemistry. 1969 Sep;8(9):3648–3655. doi: 10.1021/bi00837a023. [DOI] [PubMed] [Google Scholar]
  19. Kang A. H., Piez K. A., Gross J. Characterization of the cyanogen bromide peptides from the alpha 1 chain of chick skin collagen. Biochemistry. 1969 Apr;8(4):1506–1514. doi: 10.1021/bi00832a029. [DOI] [PubMed] [Google Scholar]
  20. Kang A. H. Studies on the location of intermolecular cross-links in collagen. Isolation of a CNBr peptide containing -hydroxylysinonorleucine. Biochemistry. 1972 May 9;11(10):1828–1835. doi: 10.1021/bi00760a015. [DOI] [PubMed] [Google Scholar]
  21. Lane J. M., Miller E. J. Isolation and characterization of the peptides derived from the alpha 2 chain of chick bone collagen after cyanogen bromide cleavage. Biochemistry. 1969 May;8(5):2134–2139. doi: 10.1021/bi00833a053. [DOI] [PubMed] [Google Scholar]
  22. Mechanic G., Gallop P. M., Tanzer M. L. The nature of crosslinking in collagens from mineralized tissues. Biochem Biophys Res Commun. 1971 Nov 5;45(3):644–653. doi: 10.1016/0006-291x(71)90465-7. [DOI] [PubMed] [Google Scholar]
  23. Miller E. J. Collagen cross-linking: identification of two cyanogen bromide peptides containing sites of intermolecular cross-link formation in cartilage collagen. Biochem Biophys Res Commun. 1971 Oct 15;45(2):444–451. doi: 10.1016/0006-291x(71)90839-4. [DOI] [PubMed] [Google Scholar]
  24. Miller E. J., Epstein E. H., Jr, Piez K. A. Identification of three genetically distinct collagens by cyanogen bromide cleavage of insoluble human skin and cartilage collagen. Biochem Biophys Res Commun. 1971 Mar 19;42(6):1024–1029. doi: 10.1016/0006-291x(71)90006-4. [DOI] [PubMed] [Google Scholar]
  25. Miller E. J. Isolation and characterization of a collagen from chick cartilage containing three identical alpha chains. Biochemistry. 1971 Apr 27;10(9):1652–1659. doi: 10.1021/bi00785a024. [DOI] [PubMed] [Google Scholar]
  26. Miller E. J., Lane J. M., Piez K. A. Isolation and characterization of the peptides derived from the alpha-1 chain of chick bone collagen after cyanogen bromide cleavage. Biochemistry. 1969 Jan;8(1):30–39. doi: 10.1021/bi00829a006. [DOI] [PubMed] [Google Scholar]
  27. Miller E. J., Lunde L. G. Isolation and characterization of the cyanogen bromide peptides from the alpha 1(II) chain of bovine and human cartilage collagen. Biochemistry. 1973 Aug 14;12(17):3153–3159. doi: 10.1021/bi00741a003. [DOI] [PubMed] [Google Scholar]
  28. Miller E. J., Martin G. R., Piez K. A., Powers M. J. Characterization of chick bone collagen and compositional changes associated with maturation. J Biol Chem. 1967 Dec 10;242(23):5481–5489. [PubMed] [Google Scholar]
  29. Miller E. J., Woodall D. L., Vail M. S. Biosynthesis of cartilage collagen. Use of pulse labeling to order the cyanogen bromide peptides in the alpha L(II) chain. J Biol Chem. 1973 Mar 10;248(5):1666–1671. [PubMed] [Google Scholar]
  30. POPENOE E. A., ARONSON R. B., VANSLYKE D. D. THE FORMATION OF COLLAGEN HYDROXYLYSINE STUDIED WITH TRITIATED LYSINE. J Biol Chem. 1965 Jul;240:3089–3092. [PubMed] [Google Scholar]
  31. Pinnell S. R., Krane S. M., Kenzora J. E., Glimcher M. J. A heritable disorder of connective tissue. Hydroxylysine-deficient collagen disease. N Engl J Med. 1972 May 11;286(19):1013–1020. doi: 10.1056/NEJM197205112861901. [DOI] [PubMed] [Google Scholar]
  32. Rauterberg J., Fietzek P., Rexrodt F., Becker U., Stark M., Kühn K. The amino acid sequence of the carboxyterminal nonhelical cross link region of the alpha 1 chain of calf skin collagen. FEBS Lett. 1972 Mar;21(1):75–79. doi: 10.1016/0014-5793(72)80167-4. [DOI] [PubMed] [Google Scholar]
  33. Siegel R. C., Martin G. R. Collagen cross-linking. Enzymatic synthesis of lysine-derived aldehydes and the production of cross-linked components. J Biol Chem. 1970 Apr 10;245(7):1653–1658. [PubMed] [Google Scholar]
  34. Stark M., Rauterberg J., Kühn K. Evidence for a non-helical region at the carboxyl terminus of the collagen molecule. FEBS Lett. 1971 Feb 19;13(2):101–104. doi: 10.1016/0014-5793(71)80209-0. [DOI] [PubMed] [Google Scholar]
  35. Stoltz M., Furthmayr H., Timpl R. Increased lysine hydroxylation in rat bone and tendon collagen and localization of the additional residues. Biochim Biophys Acta. 1973 Jun 15;310(2):461–468. doi: 10.1016/0005-2795(73)90130-x. [DOI] [PubMed] [Google Scholar]
  36. Stolz M., Timpl R., Kühn K. Non-helical regions in rat collagen 1-chain. FEBS Lett. 1972 Oct 1;26(1):61–65. doi: 10.1016/0014-5793(72)80542-8. [DOI] [PubMed] [Google Scholar]
  37. Strawich E., Nimni M. E. Properties of a collagen molecule containing three identical components extracted from bovine articular cartilage. Biochemistry. 1971 Oct 12;10(21):3905–3911. doi: 10.1021/bi00797a017. [DOI] [PubMed] [Google Scholar]
  38. Toole B. P., Kang A. H., Trelstad R. L., Gross J. Collagen heterogeneity within different growth regions of long bones of rachitic and non-rachitic chicks. Biochem J. 1972 May;127(4):715–720. doi: 10.1042/bj1270715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Trelstad R. L., Kang A. H., Igarashi S., Gross J. Isolation of two distinct collagens from chick cartilage. Biochemistry. 1970 Dec 8;9(25):4993–4998. doi: 10.1021/bi00827a025. [DOI] [PubMed] [Google Scholar]
  40. Volpin D., Veis A. Cyanogen bromide peptides from insoluble skin and dentin bovine collagens. Biochemistry. 1973 Mar 27;12(7):1452–1464. doi: 10.1021/bi00731a028. [DOI] [PubMed] [Google Scholar]
  41. Zimmermann B. K., Timpl R., Kühn K. Intermolecular cross-links of collagen. Participation of the carboxy-terminal nonhelical region of the 1-chain. Eur J Biochem. 1973 Jun;35(2):216–221. doi: 10.1111/j.1432-1033.1973.tb02828.x. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES