Hydroxylases are enzymes which add a hydroxyl group to a different type of organic compounds. The addition of this group is the first stage of aerobic oxidative degradation. Essentially, every time an organic compound begins the process of oxidative degradation in air, hydroxylases are at work on the process known as hydroxylation. This process is at work in the human body all the time and is a vital part of kidney function and the overall detoxification process of the human body. Hydroxylation facilitates the conversion of lipophilic compounds into hydrophilic, water-soluble products. These products can then be more readily removed by the kidneys, liver or skin and excreted.
Hydroxylases are also key components in the activation (or deactivation) of certain drugs such as steroids.
Hydroxylases have a range of biological functions. All of which revolve around the insertion of oxygen into C-H bonds usually derived from atmospheric oxygen. Because oxygen itself is a slow and unselective hydroxylating agent, catalysts are required to speed up the process and introduce selectivity.
Hydroxylases Interactions and functions
Hydroxylases are perhaps best known for their interactions with proteins.
The residue most frequently hydroxylated in human proteins is proline owing to the abundance of collagen in the human body. Indeed, collagen makes up about 25–35% of the protein in the human body and contains a hydroxyproline at almost every 3rd residue in its amino acid sequence.
The process of hydroxylation occurs at the γ-C atom, and hydroxyproline is formed. Due to the highly electronegative effects of oxygen, this stabilizes the secondary structure of collagen. Proline hydroxylation is also a key component of hypoxia response by way of numerous hypoxia inducible factors. In some cases, proline may instead be hydroxylated instead on its β-C atom instead of the γ-C atom. Lysine may also be hydroxylated on its δ-C atom, to form hydroxylysine (Hyl).
These three reactions are catalyzed by significant multi-subunit enzymes. These are prolyl 4-hydroxylase, prolyl 3-hydroxylase and lysyl 5-hydroxylas respectively. Iron is required for these reactions as is α-ketoglutarate and, of course, molecular oxygen to carry out the oxidation. Ascorbic acid (vitamin C) is also used to return the iron to its reduced state. Deprivation of ascorbate leads to deficiencies in proline hydroxylation, undermining the stability of collagen.
Historically, this has led to the disease scurvy which has famously been mitigated by the use of fruits that are high vitamin C. Of course, the hydroxylation of proline is by far the only example of hydroxylase interaction in the human body.
Other key examples include Phenylalanine hydroxylase (PAH) which is found in the liver and catalyzes the hydroxylation of phenylalanine to tyrosine. Likewise, Tyrosine hydroxylase (TH) is found in the brain and in the adrenal gland where it catalyzes the conversion of tyrosine to 3,4-dihydroxyphenylalanine (DOPA) which is the initial step in the biosynthesis of dopamine, norepinephrine and epinephrine.