BIOC 212 Lecture Notes - Lecture 35: Lysine, Oxidative Deamination, Kyphoscoliosis
29 May 2018
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Cell Junctions & Cell Adhesion XV
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Mechanism of Prolyl Hydroxylases
• Enzymatic mechanism (biochemical mechanism) for prolyl hydroxylases
• Dioxygenases use molecular oxygen
o Convert one oxygen to one molecule, and other oxygen to another
• Prolyl residues + oxygen + alpha-ketoglutarate co-factor
o Get hydroxylation at 4th position of proline by prolyl hydroxylase enzyme
o Decarboxylation of ketoglutarate, yielding CO2
o Succinate is produced
• One oxygen transferred to proline, and one to succinate
• Prolyl hydroxylase requires iron in its active center*
o Important for transfer & transport of electrons
o Specific binding sites for iron in center (zinc would not work)
• When substrate is present, work just as shown here
o However, sometimes no substrate present since cell does not produce the
collagen
• It oxidizes the iron 2+ to iron 3+ in absence of substrate
• Inactivates the enzyme
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• Antioxidant vitamin C is co-factor that reduces 3+ iron to functional 2+ state
o Vitamin C absolutely required (ascorbate)
o In the absence of vitamin C, get scurvy
• Diet should contain sufficient amount of vitamin C for proline
hydroxylation via prolyl hydroxylases
Defects in Collagen Hydroxylation --Scurvy
• Due to lack of vitamin C
o Not readily available for sailors on ships
o Leads to defective collagen production
o Got scurvy --skin wounds, brittle bones, teeth falling out
o Defective wound healing, rupture blood vessels, bleeding gums
o Not treated = death
o Not enough vitamin C for proline-4-hydroxylation
• Cannot enable formation of stable collagen
o A cofactor for prolyl & lysyl hydroxylases
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o Used sauerkraut since contains lots of vitamin C
o Conserved for long time --fermented; contains lots of salt
Cross-Links in Collagen –Lysyl Oxidase
