Procollagen-lysine 5-dioxygenase

Procollagen-lysine,2-oxoglutarate 5-dioxygenase is an enzyme that in humans is encoded by the PLOD1 gene. This enzyme is also commonly known as lysyl hydroxylase 1 (LH1) and plays a crucial role in the biosynthesis of collagen, a fundamental component of connective tissue. The activity of procollagen-lysine,2-oxoglutarate 5-dioxygenase is essential for the proper formation of hydroxylysine residues in collagen. These modified amino acids are critical for the stability and assembly of collagen fibers and, consequently, for the structural integrity of tissues.

Function

Procollagen-lysine,2-oxoglutarate 5-dioxygenase catalyzes the hydroxylation of lysine residues in collagen to form hydroxylysine. This post-translational modification is necessary for the subsequent glycosylation of collagen fibers, which is crucial for collagen maturation and stability. The enzyme requires iron, alpha-ketoglutarate, and oxygen to perform this reaction, making it a member of the dioxygenase family.

Genetics

The PLOD1 gene is located on the long (q) arm of chromosome 15 at position 21.1, more precisely at 15q21.1. Mutations in this gene are associated with a rare connective tissue disorder known as Kyphoscoliotic Ehlers-Danlos syndrome (kEDS), characterized by severe muscle hypotonia, kyphoscoliosis, and fragile skin.

Clinical Significance

Alterations in the activity of procollagen-lysine,2-oxoglutarate 5-dioxygenase can lead to various connective tissue disorders. The most notable condition related to mutations in the PLOD1 gene is Kyphoscoliotic Ehlers-Danlos syndrome. Patients with this condition exhibit a range of symptoms, including but not limited to, hyperelastic skin, joint hypermobility, and a high risk of cardiovascular complications due to the fragility of vascular tissue.

See Also

• Collagen
• Ehlers-Danlos Syndrome
• Connective Tissue
• Enzyme
• Hydroxylation