Hydroxylations are chemical reactions that involve the introduction of hydroxyl groups into a molecule. In the context of metabolism, enzymes provide the catalysis of hydroxylations. The corresponding enzymes are called hydroxylases.
What is hydroxylation?
In the context of metabolism, enzymes provide catalysis of hydroxylations. The corresponding enzymes are called hydroxylases. Hydroxylations are very common in chemistry and biochemistry. In general, a hydroxylation means an introduction of one or more hydroxyl groups into a molecule. The hydroxyl group consists of a hydrogen and an oxygen atom. This is how, among other things, the alcohol methanol is formed during the catalytic oxidation of methane. Catalytic addition of a water molecule to ethene produces ethanol. In biochemical processes, the addition of a hydroxyl group is catalytically supported by the so-called hydroxylases. With the aid of hydroxylases, for example, certain amino acids can be converted into important active substances in the organism. Hydroxylations, for example, convert phenylalanine into tyrosine and tyrosine in turn into DOPA. The corresponding enzymes are phenylalanine hydroxylase and tyrosine hydroxylase. With the help of tryptophan hydroxylase, tryptophan is converted into 5-hydroxytryptophan. In connective tissue, the amino acids proline and lysine are converted into hydroxyproline and hydroxylysine, respectively, by hydroxylation. There, the hydroxylated amino acids ensure the strong cross-linking of collagen and thus also the strength of the connective tissue. Another important hydroxylation reaction represents the conversion of progesterone to the corticosteroids.
Function and role
Hydroxylations are very important biochemical reactions. For example, the strength of connective tissue depends on hydroxylation reactions. In the collagen of connective tissue, the amino acids proline and lysine are present in high concentrations. Both compounds can be readily provided with an additional hydroxyl group using hydroxylases. In this process, hydroxylation takes place within the protein. Hydroxyproline is formed from proline and hydroxylysine from lysine. The enzymes proline hydroxylase and lysine hydroxylase are responsible for this with the assistance of ascorbic acid (vitamin C). The hydroxyl groups form attachment sites for sugar residues or they immediately ensure cross-linking of the individual protein molecules. 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 of dopamine. Thus, hydroxylations eventually convert important amino acids into neurotransmitters. The same applies to the hydroxylation of the amino acid tryptophan to 5-hydroxytryptophan. This compound in turn represents a precursor of serotonin, another neurotransmitter and tissue hormone. Finally, the sex hormone progesterone is converted by hydroxylation into the corticosteroids, which are hormones that perform 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 assembly of various biological agents in the organism. Disruptions in these reactions can lead to severe health problems.
Diseases and ailments
Many hydroxylations represent important intermediate steps in metabolism. When disturbances occur in hydroxylation, subsequent reaction steps are also inhibited. Thus, significant adverse health effects can occur as a result of such disruptions. 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. Drooping skin may result, with the internal organs no longer optimally protected by the connective tissue. There are a variety of mutations, each of which is very rare, 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 manifold. An acquired weakness of the connective tissue is scurvy. Scurvy occurs when there is a deficiency 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 hydroxylations of lysine and proline. Connective tissue, like other tissues in the body, is subject to constant buildup and breakdown. Prolonged absence of vitamin C results in weak connective tissue because the hydroxylations no longer function. A variety of serious symptoms occur with frequent infections, exhaustion, poorly healing wounds, skin problems, muscle breakdown, bleeding gums, high fever and much more. However, these symptoms disappear after administration of vitamin C.
Another disease related to disorders of hydroxylations is phenylketonuria. In phenylketonuria, the amino acid phenylalanine can no longer be broken down to a sufficient extent because the enzyme phenylalanine hydroxylase (PAH) is either missing or malfunctioning. Phenylalanine has a harmful effect in higher concentrations. Brain development is impaired. The growth of the skull is also stopped. The result is mental retardation. A low phenylalanine diet in childhood can prevent the onset of the disease. If tyrosine cannot be hydroxylated because tyrosine hydroxylase (TYH) is missing, the very rare Segawa syndrome develops. The neurotransmitter dopamine is no longer produced in sufficient quantities. Symptoms include gait instability and Parkinson’s-like symptoms. When tryptophan can no longer be hydroxylated due to the absence of the enzyme tryptophan hydroxylase, too little serotonin is formed. Depression often results. Finally, disorders in the hydroxylation of progesterone can lead to hormonally related diseases.
