Activation of DOPA decarboxylase by pyridoxal phosphate

Awapara, Jörge; Sandman, Robert; Hanly, C.

doi:10.1016/0003-9861(62)90220-5

Cited by 107 publications

(20 citation statements)

References 16 publications

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“…For a number of reasons, they considered that the two activities represented distinct enzymes. However, as analytical procedures improved; reports from many laboratories made it appear more likely that a single enzyme acts on both substrates (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). In view of their evidence that a partially purified enzyme from guinea pig kidney decarboxylated a large number of aromatic -amino acids, including DOPA and 5-hydroxytryptophan, Lovenberg, Weissbach, and Udenfriend (i4) proposed that the enzyme be named "aromatic i-amino acid decarboxylase".…”

mentioning

confidence: 99%

On the Identity of DOPA Decarboxylase and 5-Hydroxytryptophan Decarboxylase

Christenson

Dairman

Udenfriend

1972

Proc. Natl. Acad. Sci. U.S.A.

199

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Simultaneous immunological titration of DOPA and 5-hydroxytryptophan decarboxylase activities, from a number of tissues of various species, showed that the two activities were not distinguishable with a monospecific antiserum to hog kidney decarboxylase. Together with previous findings, these data firmly establish thb concept that in mammalian tissues the two enzyme activities are associated with a single protein, namely aromatic L-amino acid decarboxylase.The enzymatic synthesis of the biogenic amines serotonin, dopamine, and norepinephrine involves decarboxylation of the corresponding amino acids, 5-hydroxytryptophan and 3.4-dihydroxyphenylalanine (DOPA). DOPA decarboxylase (EC 4.1.1.26) was the first enzyme of the catecholamine biosynthetic pathway to be discovered (1). After the isolation and identification of serotonin (2, 3), Clark, Weissbach, and Udenfriend (4) found significant DOPA decarboxylase activity in their most highly purified preparations of 5-hydroxytryptophan decarboxylase (EC 4.1.1.28) from guinea pig kidney. For a number of reasons, they considered that the two activities represented distinct enzymes. However, as analytical procedures improved; reports from many laboratories made it appear more likely that a single enzyme acts on both substrates (5-16). In view of their evidence that a partially purified enzyme from guinea pig kidney decarboxylated a large number of aromatic -amino acids, including DOPA and 5-hydroxytryptophan, Lovenberg, Weissbach, and Udenfriend (i4) proposed that the enzyme be named "aromatic i-amino acid decarboxylase".Because the amiies resulting from decarboxylation are localized differently and are thought to have distinct physiological functions, many investigators have found it difficult to accept the hypothesis that the same enzyme is involved in both pathways. The recent demonstration that a single, homogeneous enzyme from hog kidney decarboxylates all the naturally occurring aromatic amino acids (17) is a necessary, but not a sufficient, condition for the "single enzyme" hypothesis. The possibility remains that a second enzyme may also exist, at least in some tissues. Recently, Sims and Bloom (18) have reported that, after intracisternal administration of 6-hydroxydopamine to rats, DOPA decarboxylase activities were substantially decreased in certain areas of the brain, while the 5-hydroxytryptophan decarboxylase activities were no different from controls.In the present report, evidence is presented in support of the "single enzyme" hypothesis. It is shown that DOPA decarboxylase and 5-hydroxytryptophan decarboxylase activities are not immunologically distinguishable. DOPA decarboxylase activity was assayed as described (17). The availability of carboxyl-labeled 5-hydroxytryptophan made it possible to assay 5-hydroxytryptophan decarboxylase by a basically similar method. All conditions were the same as those for the DOPA decarboxylase assay, with the following exceptions: the buffer was Tris * HCl (pH 8.

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mentioning

confidence: 99%

On the Identity of DOPA Decarboxylase and 5-Hydroxytryptophan Decarboxylase

Christenson

Dairman

Udenfriend

1972

Proc. Natl. Acad. Sci. U.S.A.

199

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“…Immunochemical and biochemical data on homogeneous AADC purified from the hog kidney support the view that a single enzyme can decar boxylate both L-DOPA and L-5-HTP (4,5). Several reports have been published, however, that indirectly support the presence of two types of AADC with relatively high activity either for L-DOPA or for L-5-HTP (3,6).…”

Section: Discussionmentioning

confidence: 82%

“…Later evidence, however, confirmed that a single enzyme acts on both substrates (4,5). Still the presence of more than one decarboxylase for aromatic amino acids in animal tissues has been suggested (3,6).…”

mentioning

confidence: 99%

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Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-dopa and L-5-hydroxytryptophan as substrates in rats.

Rahman¹,

Nagatsu²,

Sakurai³

et al. 1982

Jpn.J.Pharmacol

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Abstract-This paper describes the distribution of aromatic L-amino acid decarboxylase (AADC) activities in fourteen tissues (eight peripheral tissues and six brain regions) of semicarbazide (SC)-treated rats, using both L DOPA and L-5-hydroxytryptophan (L-5-HTP) as substrates. The distri bution of pyridoxal phosphate (PLP) was also measured in control and SC-treated rats. SC-treatment decreased the PLP concentration in all tissues (about 50-60% of control). AADC activities towards L-DOPA and L-5-HTP as substrates were also decreased significantly in almost all tissues of SC-treated rats. After the addition of exogenous PLP in vitro, AADC activities were recovered only partially in most tissues, but the recovery patterns were not parallel between L-DOPA and L-5-HTP as substrates. L-DOPA decarboxylase activity was more sensitive to PLP-deficiency than L-5-HTP decarboxylase activity in the same tissues. Serum AADC activities were decreased drastically using both L-DOPA and L-5-HTP as substrates . No serum AADC activity was detected in SC-treated rats using L-DOPA as substrate, but low activity was detected in the same sample using L-5-HTP as the substrate; both activities recovered completely after in vitro addition of 10 W PLP in the incubation mixtures.

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“…The use of fluorinated m-tyrosine analogs is supported by a strong biochemical and pharmacological rationale. For example, we find that (a) m-tyrosine is an ex cellent substrate for AAAD (Awapara et al, 1962;Srinivasan and Awapara, 1978;Borri-Voltattorni et al, 1983); the Km and Vmax values derived from Lineweaver-Burk plots indicate that L-m-tyrosine behaves as a better substrate than does L-DOPA (Borri-Voltattorni et al, 1983); (b) BBB transport of 4-FMT is significant (Melega et al, 1989); (c) newly obtained in vitro data (Barrio et al, 1995) on the neuronal vesicular transport of radiofluorinated m-tyramines indicate that, similar to dopamine, ra diofluorinated m-tyramines are substrates for the energy-dependent vesicular transporter and, there fore, stored in vesicles after its AAAD-mediated formation; (d) in in vitro evaluation of affinity at dopamine D-1 and D-2 receptor subtypes, 4-FMA had a similar affinity ( �twofold less affinity) for D-1 and D-2 binding sites than dopamine (Claudi et al, 1992). Other fluorinated phenylethylamines also show significant affinities for postsynaptic recep tors, implicating that the catechol moiety is not re quired (Cardellini et al, 1988); (e) structural re quirement analysis of substrates for the striatal do pamine reuptake carrier has shown that the 3-hydroxy group of dopamine is critical for trans port (Meiergerd and Schenk, 1994); indeed, m-tyra mine inhibited the transport of dopamine as effec tively as a catechol-containing derivative (Km = 2.6 ± 0.…”

Section: Discussionmentioning

confidence: 90%

Radiofluorinated L-m-Tyrosines: New In-Vivo Probes for Central Dopamine Biochemistry

Barrio¹,

Huang²,

Yu³

et al. 1996

J Cereb Blood Flow Metab

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Summary:In this work, we introduce 6-['sFlfluoro-L-m tyrosine (6-FMT) and compare its in-vivo kinetic and bio chemical behaviors in monkeys and rodents with those of 4-FMT and 6-['sFlfluoro-L-3,4-dihydroxyphenylalanine (DOPA) (FDOPA). These radiofluorinated m-tyrosine presynaptic dopaminergic probes, resistant to peripheral 3-0-methylation, offer a nonpharmacologicai alternative to the use of catechol-O-methyltransferase inhibitors. Like FDOPA, 4-FMT and 6-FMT are analogs that essen tially follow the L-DOPA pathway of central metabolism. After i.v. administration in nonhuman primates and ro dents, these new radiofluorinated m-tyrosine analogs ac cumulate selectively in striatal structures and allow for

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Activation of DOPA decarboxylase by pyridoxal phosphate

Cited by 107 publications

References 16 publications

On the Identity of DOPA Decarboxylase and 5-Hydroxytryptophan Decarboxylase

On the Identity of DOPA Decarboxylase and 5-Hydroxytryptophan Decarboxylase

Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-dopa and L-5-hydroxytryptophan as substrates in rats.

Radiofluorinated L-m-Tyrosines: New In-Vivo Probes for Central Dopamine Biochemistry

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