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Schematic representation of the catecholamine biosynthesis pathway with sites of aluminum interference according to the literature. Cofactors involved in each specific enzymatic reaction are highlighted in blue, while functional groups that are added/removed in red. THB = Tetrahydrobiopterin; P5P = pyridoxal phosphate; SAM = S-Adenosyl methionine; vitamin C = ascorbic acid; DβH = dopamine β-hydroxylase.

Schematic representation of the catecholamine biosynthesis pathway with sites of aluminum interference according to the literature. Cofactors involved in each specific enzymatic reaction are highlighted in blue, while functional groups that are added/removed in red. THB = Tetrahydrobiopterin; P5P = pyridoxal phosphate; SAM = S-Adenosyl methionine; vitamin C = ascorbic acid; DβH = dopamine β-hydroxylase.

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Context 1
... they find their way in the correct be- havior of both the sympathetic and parasympathetic systems, where they play an important role in the fight-or-flight response and, in general, in the body's response to stress. 95 L-DOPA, dopamine, noradrenaline (norepinephrine) and adre- naline (epinephrine) are synthesized from the aminoacid L-tyrosine (Fig. 6); the resulting catecholamine biosynthesis pathway involves several enzymes, substrates, cofactors, metal ions and regulatory mechanisms that are highly interjoined with other metabolic pathways, leading to a complex and finely controlled network. 93 Hence, the perturbation, inter- ference or impairment of such an intricate network is ...
Context 2
... best of our knowledge) the literature regarding Al(III) and catecholamines, and evaluate some other possible mechanisms of Al(III) interference that could be assessed in future. For that purpose, an up-to-date representa- tion of the catecholamine biosynthesis pathway with sites of aluminum influence (according to the literature) is proposed in Fig. ...
Context 3
... an enzyme that contains Cu(II) metal ions in its active site, converts dop- amine to noradrenaline using vitamin C as a cofactor. Finally, catechol-O-methyltransferase is involved in the regulation (inactivation) of catecholamine levels by methylation of their hydroxyl groups, using Mg(II) and S-adenosyl methionine (SAM) as cofactors (Fig. ...
Context 4
... interestingly, Al(III) inhibits O-methylation (COMT) but not N-methylation ( phenylalanine N-methyltransferase, PNMT) 101,102 of catecholamines. PNMT is the enzyme in charge of the synthesis of adrenaline through N-methylation of noradrenaline (Fig. 6). These findings were interpreted in terms of the formation of strong and stable Al-catecholamine complexes, in which the methylation at the oxygen atoms of the catecholate would be affected by the binding of the metal, whereas the methylation at the terminal amino group of nor- adrenaline would be unaffected since this group is not ...
Context 5
... explain its non-sensitivity to the presence of Al(III) reported in the literature. 101,102 The catecholamine pathway contains two main enzymatic regulators that ensure the correct homeostasis of the levels of these neurotransmitters: one is the previously discussed cate- chol-O-methyltransferase, and the second one is monoamine oxidase (MAO, Fig. 6). MAO enzymes catalyze the oxidative de- amination of biological monoamines using flavin adenine dinucleotide (FAD) as cofactors, thus leading to their inacti- vation. Different mechanisms of action (at least four) have been proposed for MAO catalytic activity, although the exact one is still not well understood. 110 Interestingly, ...
Context 6
... far we have discussed the role that aluminum might have with respect to the enzymatic machineries acting on the catecholamine pathway. However, there are many low-mole- cular-mass organic cofactors that are pivotal for the correct be- havior of these enzymes and therefore could be important targets of this metal (Fig. ...
Context 7
... C, also known as ascorbic acid, is an essential vitamin required as a cofactor by DBH for the conversion of dopamine into noradrenaline (Fig. 6). Perturbation of vitamin C metabolism in the brain has been related to the occurrence of severe neurodegenerative diseases. 119 Moreover, several studies highlight the chelation properties of vitamin C and its interaction with aluminum has been investigated. [120][121][122][123] In this sense, the structure and binding mode of the ...
Context 8
... investigated. [120][121][122][123] In this sense, the structure and binding mode of the Al-ascorbate complexes in solution have been unveiled and clarified by means of both experimental and DFT computations. 123 Therefore, vitamin C might be a potential Al(III) target, and the resulting complex might be involved in the impairment of DHB activity (Fig. ...

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