Osteolathyrism

Osteolathyrism is a collagen cross-linking deficiency brought on by dietary over-reliance on the seeds of Lathyrus sativus. It is commonly seen in combination with neurolathyrism and angiolathyrism in impovershed areas where famine demands reliance on a crop with known detrimental effects. Osteolathyrism is caused by a variety of osteolathyrogenic compounds, specifically exitatory amino-compounds. The most widely-studied of these compound is beta-aminopropionitrile (BAPN) which exerts its deleterious effect by an unknown yet potently irreversible mechanism. Other instigators are the ureides, semicarbazide and thiosemicarbazide, which are believed to chelate the prosthetic Cu-(II)-bipyridine cofactor complex in the enzyme lysyl oxidase.

beta-aminopropionitrile (BAPN)

Lysyl oxidase is an important enzyme for the creation of crosslinks between collagen triple-helices in connective tissue. By oxidizing the terminal amino group of lysine, an aldehyde is created. These aldehydes can undergo a couple of reactions with neighboring aldehydes or amines to create strong covalent cross-links between collagen tertiary structures in bone and cartilage. The main product of these reactions is the aldimine compound, dehydrohyroxylysinonorleucine.

dehydrohyroxylysinonorleucine

This unique crosslink can be formed by the Schiff base mechanism in which the lone pair of electrons on a primary amine react with the carbonyl carbon of an aldehyde. Other crosslinks include the formation of an α,β-unsaturated ketone via the Aldol condensation and hydroxylysinonorleucine.

If these crosslinks are not formed, as in the case of osteolathyrism, the synthesis of strong mesenchymal and mesodermal tissue is inhibited. Symptoms of osteolathyrism include weakness and fragility of connective tissue (i.e., skin, bones, and blood vessels [angiolathyrism]) and the paralysis of the lower extremities associated with neurolathyrism. For these reasons, compounds containing lathyrogens should be avoided during pregnancy and growth of a child.