Body processes

Hydroxylation – function, role and diseases


Hydroxylations are chemical reactions in which hydroxyl groups are introduced into a molecule. As part of the metabolism, enzymes catalyze the hydroxylations . The corresponding enzymes are called hydroxylases.

What is Hydroxylation?

Hydroxylations are very common in chemistry and biochemistry. In general, hydroxylation means introducing one or more hydroxyl groups into a molecule. The hydroxyl group consists of one hydrogen and one oxygen atom. For example, the alcohol methanol is formed during the catalytic oxidation of methane . Ethanol is formed by the catalytic addition of a water molecule to ethene.

In biochemical processes, the addition of a hydroxyl group is supported catalytically by so-called hydroxylases. With the help of hydroxylases, for example, certain amino acids can be converted into important active substances in the organism. For example, phenylalanine is converted into tyrosine and tyrosine into DOPA by hydroxylation . The corresponding enzymes are phenylalanine hydroxylase and tyrosine hydroxylase. Tryptophan is converted into 5-hydroxytryptophan with the help of tryptophan hydroxylase.

In the connective tissue , the amino acids proline and lysine are converted by hydroxylation into hydroxyproline and hydroxylysine , respectively . The hydroxylated amino acids ensure the strong cross-linking of collagen and thus also the strength of the connective tissue.

Another important hydroxylation reaction is the conversion of progesterone to corticosteroids .

Function & task

Hydroxylations are very important biochemical reactions. The strength of the connective tissue depends on hydroxylation reactions. The amino acids proline and lysine are present in high concentrations in the collagen of the connective tissue. Both compounds can easily be provided with an additional hydroxyl group using hydroxylases. The hydroxylation takes place within the protein . Hydroxyproline is formed from proline and hydroxylysine from lysine. The enzymes proline hydroxylase and lysine hydroxylase with the participation of ascorbic acid ( vitamin C) responsible. The hydroxyl groups form attachment points for sugar residues or they ensure that the individual protein molecules are crosslinked. This cross-linking results in a strong and flexible connective tissue.

Another hydroxylation reaction is the conversion of the amino acid phenylalanine into tyrosine. This reaction is important for eukaryotic organisms because high concentrations of phenylalanine in the cell are harmful. Tyrosine is further hydroxylated to L-DOPA. L-DOPA is a catecholamine and the precursor to dopamine . Important amino acids are finally converted into neurotransmitters by hydroxylation .

The same applies to the hydroxylation of the amino acid tryptophan to 5-hydroxytryptophan. This compound in turn is a precursor to serotonin , another neurotransmitter and tissue hormone .

Finally, the sex hormone progesterone is converted by hydroxylation into corticosteroids, which as hormones take on a variety of tasks in the body. These include the glucocorticoid cortisol and the mineralocorticoid aldosterone . These hormones are synthesized by hydroxylations of progesterone and conversions of the hydroxyl groups to keto or aldehyde groups .

Overall, hydroxylations are responsible for the build-up of different biological active substances in the organism. Disturbances in these reactions can lead to serious health problems.

Diseases & Ailments

Many hydroxylations represent important intermediate steps in the metabolism. If there are problems with the hydroxylation, the subsequent reaction steps are also inhibited. Significant health impairments can occur as a result of such disorders. For example, inhibition of the hydroxylation of proline and lysine in connective tissue collagen leads to connective tissue weakness . In some cases, the connective tissue can be overstretched. It can lead to sagging skin , whereby the internal organs are no longer optimally protected by the connective tissue.

There are many, but very rare mutations that lead to defects in the structure of the enzymes lysine hydroxylase or proline hydroxylase. Each individual genetic defect shows different symptoms. What they all have in common, however, is the weakness of the connective tissue. The other symptoms are varied.

Scurvy is an acquired connective tissue weakness. Scurvy occurs when there is a lack of vitamin C. Vitamin C or ascorbic acid supports the two hydroxylases mentioned above. If the body is not supplied with vitamin C, lysine and proline hydroxylase can hardly support the hydroxylation of lysine and proline. The connective tissue, like the other tissues in the body, is subject to constant assembly and breakdown processes. If there is a long-term lack of vitamin C, weak connective tissue develops because the hydroxylation no longer functions. There are a variety of serious symptoms with frequent infections , exhaustion , poorly healing wounds , skin problems,Muscle wasting , bleeding gums , high fever and much more. However, these symptoms disappear after administration of vitamin C.

Phenylketonuria is another disease associated with hydroxylation disorders . In phenylketonuria, the amino acid phenylalanine can no longer be sufficiently broken down because the enzyme phenylalanine hydroxylase (PAH) is either missing or has a malfunction. Phenylalanine is harmful in higher concentrations. Brain development is impaired . The growth of the skull is also stopped. The result is a mental handicap . A diet low in phenylalanine during childhood can prevent the onset of the disease.

If tyrosine cannot be hydroxylated due to the lack of tyrosine hydroxylase (TYH), the very rare Segawa syndrome develops . The neurotransmitter dopamine is no longer produced in sufficient quantities. Unsteady gait and Parkinson’s- like symptoms appear as symptoms .

If tryptophan can no longer be hydroxylated due to the lack of the enzyme tryptophan hydroxylase, too little serotonin is formed. Depression is common . Finally, disturbances in the hydroxylation of progesterone can lead to hormone-related diseases.

Lisa Newlon
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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.