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Hydroxylation is a chemical process that introduces a hydroxyl group (-OH) into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air. It is extremely important in detoxification since hydroxylation converts lipophilic compounds into water-soluble (hydrophilic) products that are more readily excreted. Some drugs (e.g. steroids) are activated or deactivated by hydroxylation.

Chemical concepts[edit source | edit]

The hydroxylation process involves conversion of a CH group into a COH group. Hydroxylation is an oxidative process. The oxygen that is inserted into the C-H bond is usually derived from atmospheric oxygen (O2). Since O2 itself is a slow hydroxylating agent, catalysts are required to accelerate the pace of the process.

Biological hydroxylation[edit source | edit]

The principal hydroxylation agent in nature is cytochrome P-450, hundreds of variations of which are known. Other hydroxylating agents include flavins.^[1]

Hydroxylation of proteins[edit source | edit]

The principal residue to be hydroxylated in proteins is proline. The hydroxylation occurs at the γ-C atom, forming hydroxyproline (Hyp), an essential element of collagen, in turn a necessary element of connective tissue. Proline hydroxylation is also a vital component of hypoxia response via hypoxia inducible factors. In some cases, proline may be hydroxylated instead on its β-C atom. Lysine may also be hydroxylated on its δ-C atom, forming hydroxylysine (Hyl).

These three reactions are catalyzed by very large, multi-subunit enzymes prolyl 4-hydroxylase, prolyl 3-hydroxylase and lysyl 5-hydroxylase, respectively. These reactions require iron (as well as molecular oxygen and α-ketoglutarate) to carry out the oxidation, and use ascorbic acid (vitamin C) to return the iron to its oxidized state. Deprivation of ascorbate leads to deficiencies in proline hydroxylation, which leads to less stable collagen, which can manifest itself as the disease scurvy. Since citrus fruits are rich in vitamin C, British sailors were given limes to combat scurvy on long ocean voyages; hence, they were called "limeys".

Examples of hydroxylases[edit source | edit]

17α-Hydroxylase
Cholesterol 7 alpha-hydroxylase
Dopamine β-hydroxylase
Phenylalanine hydroxylase
Tyrosine hydroxylase

References[edit source | edit]

^ Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISBN 1-57259-153-6.

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English Journal

Cytochrome P4504f, a potential therapeutic target limiting neuroinflammation.

Sehgal N, Agarwal V, Valli RK, Joshi SD, Antonovic L, Strobel HW, Ravindranath V.SourceDivision of Molecular and Cellular Neuroscience, National Brain Research Centre, Nainwal Mode, Manesar 122050, Haryana, India.
Biochemical pharmacology.Biochem Pharmacol.2011 Jul 1;82(1):53-64. Epub 2011 Apr 2.
Inflammatory processes are involved in the pathogenesis and/or progression of acute central nervous system (CNS) infection, traumatic brain injury and neurodegenerative disorders among others indicating the need for novel strategies to limit neuroinflammation. Eicosanoids including leukotrienes, par
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A Hypoxia-Induced Positive Feedback Loop Promotes Hypoxia-Inducible Factor 1{alpha} Stability through miR-210 Suppression of Glycerol-3-Phosphate Dehydrogenase 1-Like.

Kelly TJ, Souza AL, Clish CB, Puigserver P.SourceDana-Farber Cancer Institute, 44 Binney Street, CLSB11144, Boston, MA 02115. pere_puigserver@dfci.harvard.edu.
Molecular and cellular biology.Mol Cell Biol.2011 Jul;31(13):2696-706. Epub 2011 May 9.
Oxygen-dependent regulation of the transcription factor HIF-1α relies on a family of prolyl hydroxylases (PHDs) that hydroxylate hypoxia-inducible factor 1α (HIF-1α) protein at two prolines during normal oxygen conditions, resulting in degradation by the proteasome. During low-oxygen conditions,
PMID 21555452

Japanese Journal

Effect of cell-surface hydrophobicity on bacterial conversion of water-immiscible chemicals in two-liquid-phase culture systems(MICROBIAL PHYSIOLOGY AND BIOTECHNOLOGY)

Hamada Takahiro,Maeda Yusuke,Matsuda Hiroyuki,Sameshima Yuka,Honda Kohsuke,Omasa Takeshi,Kato Junichi,Ohtake Hisao
Journal of bioscience and bioengineering 108(2), 116-120, 2009-08
… opacus transformants were examined for their ability to hydroxylate monoaromatics in an aqueous single-liquid-phase culture, the reaction velocity was markedly lower than that observed in the A/O two-liquid-phase culture. …
NAID 110007359737

The Structure-Activity Correlation on the Inhibitory Effects of Flavonoids on Cytochrome P450 3A Activity(Biopharmacy)

TSUJIMOTO Masayuki,HORIE Maya,HONDA Hiroko,TAKARA Kohji,NISHIGUCHI Kohshi
Biological & pharmaceutical bulletin 32(4), 671-676, 2009-04-01
… The activity of testosterone 6β-hydroxylate was evaluated to quantify CYP3A activity. …
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