Hydroxylase is a kind of oxygenase. It is an enzyme that catalyzes the reaction of forming hydroxides (phenols and alcohols) using oxygen molecules. In the synthesis of tyrosine from phenylalanine, (phenylalanine hydroxylase) and aminophenol (aniline-4-hydroxylase) from aniline. Hydroxylases are present in reactions such as the synthesis of steroids (squalene hydroxylase) from squalene (squalene) and hydroxylation of steroids (various steroid hydroxylases). Among the hydroxylases, P-450, F-AD and the like are mostly used as constituents. In most cases, it is present in various organ microsomes. It is also present in the mitochondria of the pararenal cortex.
Examples of Hydroxylases Proteins
CYP17A1 is a member of the cytochrome P450 superfamily of enzymes located in the endoplasmic reticulum. The proteins in this family are monooxygenases, which catalyze the synthesis of cholesterol, steroids and other lipids, and are involved in drug metabolism. CYP17A1 has both 17α-hydroxylase activity and 17,20-lyase activity. The 17α-hydroxylase activity of CYP17A1 is necessary for the production of glucocorticoids (such as cortisol), but the hydroxylase and 17,20-lyase activity of CYP17A1 is achieved by converting 17α-hydroxypregnenolone to Hydroepiandrosterone is required to produce androgens and estrogen steroids (DHEA). Mutations in this gene have been linked to isolated steroid-17α-hydroxylase deficiency, 17α-hydroxylase/17,20-lyase deficiency, pseudohermaphrodite and adrenal hyperplasia. In addition, 17,20-lyase activity depends on cytochrome P450 oxidoreductase (POR), cytochrome b5 (CYB5), and phosphorylation. Cytochrome b5 can promote 17,20 lyase activity of CYP17A1 and can provide a second electron to certain P450s. In humans, testosterone production by CYP17A1 through pregnenolone to 17-OHPreg and DHEA requires POR. Human P450c17 is phosphorylated on serine and threonine residues by cAMP-dependent protein kinases. Phosphorylation of P450c17 increased 17,20-lyase activity, while dephosphorylation virtually eliminated this activity.
Figure 1. Human Cytochrome P450 CYP17A1 in complex with Abiraterone.
Cholesterol 7 alpha-hydroxylase
The disruption of classical bile acid synthesis in mice by CYP7A1 results in a lighter phenotype of increased postnatal death or elevated serum cholesterol. The latter is similar to that in humans, in which CYP7A1 mutations are associated with high plasma low-density lipoprotein and liver cholesterol levels and insufficient bile acid excretion. There is also a synergy between plasma low-density lipoprotein cholesterol (LDL-C) and the risk of coronary heart disease (CAD). Glucose signal transduction also induces CYP7A1 gene transcription through epigenetic regulation of histone acetylation status. Under normal and diabetic conditions, glucose-induced bile acid synthesis is important for metabolic control of glucose, lipid, and energy homeostasis. CYP7A1-rs3808607 and APOE subtypes are related to the extent of circulating LDL cholesterol reduction caused by intake of PS, and can be used as potential predictive genetic markers to identify those individuals who will cause the highest LDL cholesterol reduction in PS. Genetic variation of CYP7A1 affects its expression and therefore may affect the risk of gallstone disease and gallbladder cancer.
Figure 2. Cartoon representation of the molecular structure of protein registered with 3dax code.
Dopamine β-hydroxylase (DBH)
Dopamine β-hydroxylase (DBH), also known as dopamine β-monooxygenase, is an enzyme encoded by the DBH gene in humans. Dopamine beta-hydroxylase catalyzes the conversion of dopamine to norepinephrine. Dopamine is converted to norepinephrine by dopamine beta-hydroxylase. Ascorbic acid is used as a cofactor. The three substrates of the enzyme are dopamine, vitamin C (ascorbate) and O2. The products are norepinephrine, dehydroascorbic acid and H2O. DBH is a 290 kDa copper-containing oxygenase consisting of four identical subunits. Its activity requires ascorbic acid as a cofactor. It is the only enzyme involved in the synthesis of small molecule neurotransmitters involved in membrane binding, making norepinephrine the only known transmitter synthesized within the vesicle. It is expressed in noradrenergic neurons in the central nervous system (ie, the blue-spot locus) and in the peripheral nervous system (ie, the sympathetic ganglia), as well as in the chromaffin cells of the adrenal medulla.
Figure 3. Dopamine is converted to norepinephrine by the enzyme dopamine β-hydroxylase. Ascorbic acid serves as a cofactor.
PAH has been proposed using an allosteric morphine model. Mammalian PAHs exist in an equilibrium consisting of two differently-structured tetramers, one or more dimeric forms of which are part of this equilibrium. This behavior is consistent with the mechanism of deconstruction and deformation. Many studies have shown that mammalian PAHs exhibit behaviors comparable to bilirubinogen synthase (PBGS), and various factors such as pH and ligand binding have been reported to affect enzyme activity and protein stability.
Figure 4. Protein structure of PAH.
Tyrosine hydroxylase or tyrosine 3-monooxygenase is an enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA). Tyrosine hydroxylase catalyzes the hydroxylation of L-tyrosine during glycosylation. The meta position of L-3,4-dihydroxyphenylalanine (L-DOPA) was obtained. The enzyme is an oxygenase, which means it uses molecular oxygen to hydroxylate its substrate. One oxygen atom in O2 is used to hydroxylate the tyrosine molecule to obtain L-DOPA, and the other oxygen atom is used to hydroxylate the cofactor. Like other aromatic amino acid hydroxylases (AAAHs), tyrosine hydroxylase uses the cofactor tetrahydrobiopterin (BH4) under normal conditions, although other similar molecules can also act as cofactors for tyrosine hydroxylase factor.
Figure 5. Tyrosine hydroxylase from rat showing two of its domains.