The in vitro binding of acetaldehyde to collagen studied by neutron diffraction.

The location of acetaldehyde binding sites in the axial unit cell of tendon collagen was investigated by neutron diffraction. Acetaldehyde forms spontaneous cross-links with specific residues in collagen. The use of deuterated acetaldehyde increased the neutron scattering length of these groups. The introduction of deuterated acetaldehyde at specific locations allowed the acetaldehyde-reacted collagen to be treated as multiple isomorphous derivatives for neutron fibre diffraction. The low resolution axially projected structure was determined using amplitudes of the first eight meridional reflections (d = 67 nm). Results indicate that the process of acetaldehyde labelling takes place at different rates at different sites within the collagen fibril. The position of acetaldehyde attachment correlates well with the position of lysine and hydroxylysine residues especially in the regions of the molecular termini. This information is relevant to the process of cirrhosis and fibrosis of the liver since adduction of collagen by acetaldehyde may interfere with normal Schiff base cross-link formation at the C- and N-termini. This may result in subsequent alterations in the intra- and inter-molecular cross-linking pattern of collagen molecules.