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Inflammation
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Hydroxyproline is an important constituent of collagen. The formation of this compound by hydroxylation is also catalyzed by NADH:monodehydroascorbic acid transdehydrogenase. First, proline is incorporated into the collagen and becomes hydroxylated after the peptide chain is produced.217 Similarly to proline, lysine is also incorporated into the collagen and subsequently hydroxylated to hydroxylysine. The hydroxylation of these two compounds represents a key step in collagen synthesis. Hydroxyproline and hydroxylysine take part in cross-linking of peptide chains which are necessary for the collagen molecule to become finally assembled into a typical triple helix. Besides ascorbic acid and molecular oxygen, the hydroxylation process requires ferrous iron and α-ketoglutarate.
Ascorbate as an Enzyme Cofactor
Published in Qi Chen, Margreet C.M. Vissers, Vitamin C, 2020
Margreet C.M. Vissers, Andrew B. Das
Dopamine β-hydroxylase is found in the chromaffin granules of the adrenal medulla and sympathetic neurons, where it catalyzes the hydroxylation of the catecholamine neurotransmitter dopamine to generate norepinephrine (Table 5.1 and Figure 5.5) [250]. The reaction proceeds in two distinct steps; ascorbate-mediated reduction of Cu2+ in the enzyme active site followed by Cu+-mediated activation of oxygen to hydroxylate dopamine to the norepinephrine product (Figure 5.5). Ascorbate is consumed stoichiometrically in this reaction cycle with equimolar production of semidehydroascorbate and dopamine [251–254]. The Km for ascorbate is ∼0.6 mM [243,251], and the adrenals and neurons supporting this activity contain 10–20 mM ascorbate, the highest concentrations in the body [5,36,37,49,51]. These tissues accumulate ascorbate very efficiently and retain their content when plasma supply is limited [114], suggesting adaptation to ensure ongoing optimal dopamine β-hydroxylase activity.
The vitamins
Published in Geoffrey P. Webb, Nutrition, 2019
Vitamin D must undergo two hydroxylation reactions to convert it to its active form. Firstly, an hydroxyl group is added to carbon 25 in the liver and a second hydroxyl added at carbon 1 in the kidney to give 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D respectively (see Figure 15.3).
Vitamin D attenuates biofilm-associated infections via immunomodulation and cathelicidin expression: a narrative review
Published in Expert Review of Anti-infective Therapy, 2023
Ruby Benson, Mazhuvancherry Kesavan Unnikrishnan, Shilia Jacob Kurian, Saleena Ummer Velladath, Gabriel Sunil Rodrigues, Raghu Chandrashekar Hariharapura, Anju Muraleedharan, Dinesh Bangalore Venkateshiah, Barnini Banerjee, Chiranjay Mukhopadhyay, Aieshel Serafin Johnson, Murali Munisamy, Mahadev Rao, Benson Mathai Kochikuzhyil, Sonal Sekhar Miraj
Vitamin D in food/skin is activated by two successive stages of hydroxylation. Ingested vitamin D gets bound to vitamin D binding protein (VDBP), a serum glycoprotein with a single binding site for all vitamin D metabolites [23–25]. First, vitamin D is hydroxylated at the C-25th position in the liver by cytochrome P450 (CYP) 2R1 to form 25-hydroxy vitamin D, or calcidiol. Secondly, in the kidney, CYP27B1 adds a hydroxyl group at C-1 to generate 1,25-dihydroxy vitamin D, the functional form that mediate genomic actions [26–28]. Hypocalcemia, fibroblast growth factor 23, and parathyroid hormone, regulate renal hydroxylases [29]. VDBP’s high affinity for 25-hydroxy vitamin D increases the levels of circulating 25-hydroxy vitamin D, thereby assuaging vitamin D deficiency [24,25].
In silico prediction of post-translational modifications in therapeutic antibodies
Published in mAbs, 2022
Hydroxylation is an enzymatic modification that is catalyzed by hydroxylases. Hydroxylation can occur at arginine, tyrosine, Trp, and phenylalanine, but it is more common for Pro and Lys.121 During hydroxylation, a hydroxyl (OH) group is added to Pro or Lys residues. As a result, Pro is converted to 3-hydroxyPro or 4-hydroxyPro, whereas Lys is converted to 5-hydroxyLys.122 Hydroxylation of Lys and Pro residues at consensus motifs (Xaa-Lys-Gly or Xaa-Pro-Gly) is common in collagen, where hydroxylation helps stabilize the collagen triple-helix.123 Common parameters for designing hydroxylation predictors include solvent exposure, intrinsic disorder, hydrophilicity, and sequence.122,123 Hydroxylation sites tend to be disordered, exposed, and enriched with Pro and Gly residues.124
Role of amino acids at positions 34, 296, and 486 of cytochrome P450 2D6 in the stimulatory and inhibitory effects of psychotropic agents on dopamine formation from p-tyramine
Published in Xenobiotica, 2021
Toshiro Niwa, Juri Arima, Yurina Michihiro
Tyramine is present in exogenously fermented foods such as cheese and wine, as well as endogenously in the brain (Philips et al. 1978). Dopamine is a neurotransmitter and precursor of noradrenaline and adrenaline; it is biotransformed from p-tyramine through CYP2D6-catalysed ring-hydroxylation as well as from L-3,4-dihydroxyphenylalanine (L-DOPA, levodopa) in the brain (Hiroi et al. 1998; Funae et al. 2003; Haduch et al. 2013; Niwa et al. 2017). Interestingly, we previously found that Vmax values for dopamine formation catalysed by CYP2D6.1, CYP2D6.2, and CYP2D6.10 gradually increased with increasing concentrations of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) (Niwa et al. 2018; Niwa and Sugimoto 2019). Km values for dopamine formation by CYP2D6.2 and CYP2D6.10, but not CYP2D6.1, gradually decreased with increasing concentrations of fluoxetine, an SSRI, whereas another SSRI, paroxetine, competitively inhibited the activities catalysed by all CYP2D6 variants investigated (Niwa et al. 2018; Niwa and Sugimoto 2019). These results indicate that fluvoxamine and fluoxetine, which have a trifluoromethyl group, but not paroxetine (Figure 2), stimulated dopamine formation.