On the Identity of DOPA Decarboxylase and 5-Hydroxytryptophan Decarboxylase

Christenson, James G.; Dairman, Wallace; Udenfriend, Sidney

doi:10.1073/pnas.69.2.343

Cited by 199 publications

(63 citation statements)

References 25 publications

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“…The enzyme aromatic amino acid decarboxylase has been reported (22) to be capable of decarboxylating a variety of amino acids including dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5HTP). Immunological evidence has been presented to suggest the identity of DOPA decarboxylase with 5HTP decarboxylase (23). Their data indicate that ten times more antibody, prepared against the hog kidney decarboxylase, per unit of enzyme activity was required for the complete inhibition of the decarboxylase activity of rat brain as compared to the enzyme activity of hog kidney.…”

Section: Monoaminesmentioning

confidence: 96%

Neurobiology of Pyridoxine

Dakshinamurti

1982

Advances in Nutritional Research

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Pyridoxal 5'-phosphate (PLP) is the major coenzymatic form of pyridoxine. There are over one hundred known pyridoxal 5'-phosphate-dependent reactions, most of which are involved in the metabolism of various amino acids . Pyridoxamine 5'-phosphate can function in aminotransf erase reactions by the cyclic regeneration of the two active phosphate forms. Pyridoxal 5'-phosphate-dependent reactions studied in the nervous system are involved in the catabolism of various amino acids.The putative neurotransmitters , dopamine, norepinephrine , serotonin , histamine , aminobutyric acid and taurine , as well as the sphingoiipids and poly amines are synthesized by PLP-dependent enzymes. Of these enzymes, three ( glutamic acid decarboxylase , 5-hydroxytryptophan decarboxylase and crnithine decarboxylase) seem to have crucial roles (Fig. '). The clinical effects of pyridoxine deficiency can be explained on the basis of the known decreases in the activities of these enzymes (1). EXPERIMENTAL PYRIDOXINE DEFICIENCY IN THE NEONATE RATDakshinamurti and Stephens ( 2) first reported the production of congenital pyridoxine deficiency .Our observations extended the "chronic fetal distress" hypothesis of Gruenwald ( 3) to include effects on the development of the central nervous system. We later showed that a deficiency of pyridoxine in rat pups could be produced by depriving the dam of dietary pyridoxine during lactation (4). Such a deficiency has been characterized using biochemical and electrophysiological parameters. The electroencephalogram (EEG)

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Section: Monoaminesmentioning

confidence: 96%

Neurobiology of Pyridoxine

Dakshinamurti

1982

Advances in Nutritional Research

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“…More specifically, the key step in the formation of the aromatic amines dopamine, epinephrine, and norepinephrine is catalyzed by a single enzyme named 3,4-dihydroxyphenylalanine (DOPA) decarboxylase (DDC, EC 4.1.1.28) since it can convert L-DOPA into dopamine (Christenson et al 1972, Zhu & Juorio 1995, Berry et al 1996. Because this enzyme may also decarboxylate other aromatic amino acids, such as 5-hydroxytryptophan, tryptophan, phenylalanine, and tyrosine, producing their corresponding amines 5-hydroxytryptamine, tryptamine, phenylethylamine, and tyramine, it is also named aromatic L-amino acid decarboxylase (AADC).…”

Section: Introductionmentioning

confidence: 99%

Opposite sexual dimorphism of 3,4-dihydroxyphenylalanine decarboxylase in the kidney and small intestine of mice

López-Contreras

Galindo²,

López‐García³

et al. 2007

Journal of Endocrinology

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3,4-Dihydroxyphenylalanine decarboxylase (DDC; also known as L-amino acid decarboxylase) is involved in the synthesis of dopamine, norepinephrine, and serotonin, and also acts as an androgen receptor co-regulator protein. In contrast to other amino acid decarboxylases that are modulated by sex hormones, little is known about the influence of these hormones on DDC regulation. In the present work, we studied the influence of gender in the expression of DDC in different mouse tissues. Among the different organs studied, including brain, liver, kidney, intestine, heart, adrenal gland, and skeletal muscle, only kidney and small intestine showed a sex-dependent dimorphism in DDC expression. In the kidney, levels of DDC activity, DDC mRNA, and protein were remarkably higher in females than in males. On the contrary, in the small intestine, male mice displayed higher levels of DDC activity than females but they did not correlate precisely with mRNA levels. This dimorphism was dependent on androgens, since male castration and treatment of female mice with testosterone propionate, oppositely affected DDC levels in kidney and small intestine. However, estrogen ablation or treatment with estradiol did not significantly affect DDC activity in these tissues. Immunocytochemical analysis revealed that DDC was mainly located in the proximal straight tubular cells of the kidney and in the cytoplasm of enterocytes. These data and the fact that renal DDC inversely correlated with renal sodium reabsorption suggest that renal and intestinal gender dimorphism in DDC could be related to sexrelated differences in sodium balance observed between males and females.

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“…striatum and nucleus accumbens) (20,23,24). In the second enzymatic step of DA synthesis, aromatic amino acid decarboxylase (AADC) converts DOPA into DA (28). Less information is available regarding the subcellular distribution of AADC in monoaminergic neurons and chromaffin cells.…”

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confidence: 99%

A Biochemical and Functional Protein Complex Involving Dopamine Synthesis and Transport into Synaptic Vesicles

Cartier

Parra

Baust

et al. 2010

Journal of Biological Chemistry

115

103

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Synaptic transmission depends on neurotransmitter pools stored within vesicles that undergo regulated exocytosis. In the brain, the vesicular monoamine transporter-2 (VMAT 2 ) is responsible for the loading of dopamine (DA) and other monoamines into synaptic vesicles. Prior to storage within vesicles, DA synthesis occurs at the synaptic terminal in a two-step enzymatic process. First, the rate-limiting enzyme tyrosine hydroxylase (TH) converts tyrosine to di-OH-phenylalanine. Aromatic amino acid decarboxylase (AADC) then converts di-OH-phenylalanine into DA. Here, we provide evidence that VMAT 2 physically and functionally interacts with the enzymes responsible for DA synthesis. In rat striata, TH and AADC co-immunoprecipitate with VMAT 2 , whereas in PC 12 cells, TH co-immunoprecipitates with the closely related VMAT 1 and with overexpressed VMAT 2 . GST pull-down assays further identified three cytosolic domains of VMAT 2 involved in the interaction with TH and AADC. Furthermore, in vitro binding assays demonstrated that TH directly interacts with VMAT 2 . Additionally, using fractionation and immunoisolation approaches, we demonstrate that TH and AADC associate with VMAT 2 -containing synaptic vesicles from rat brain. These vesicles exhibited specific TH activity. Finally, the coupling between synthesis and transport of DA into vesicles was impaired in the presence of fragments involved in the VMAT 2 /TH/AADC interaction. Taken together, our results indicate that DA synthesis can occur at the synaptic vesicle membrane, where it is physically and functionally coupled to VMAT 2 -mediated transport into vesicles.Monoamines, including dopamine (DA), 3 norepinephrine (NE), and serotonin (5-HT), are neurotransmitters that play major roles in a variety of brain functions, including emotion, reward, cognition, memory, attention, locomotion, and stress control (1-6). In neurons and neuroendocrine cells, monoamines are stored in large dense core vesicles (LDCVs) and small synaptic vesicles (SVs) (7-11) that undergo regulated exocytosis through a complex network of protein-protein interactions (12). Loading of monoamines into LDCVs and SVs of neurons and neuroendocrine cells is mediated by two vesicular monoamine transporter isoforms: VMAT 1 (13) and VMAT 2 (14). These transporters contain 12 putative transmembrane domains with both the N and C termini facing the cytosolic side of the vesicle membrane. VMAT 1 is mostly present in LDCVs of neuroendocrine cells, including chromaffin and PC12 cells, whereas VMAT 2 is primarily expressed by monoaminergic neurons of the central nervous system (15). In midbrain DA neurons, VMAT 2 is sorted to LDCVs and SVs in axon terminals and to LDCVs and tubulo-vesicular structures in the somatodendritic compartment (7)(8)(9)(10)(11)15).It is generally accepted that VMAT 2 transports DA that has been previously synthesized in the cytosolic compartment of the presynaptic terminal (16). DA synthesis requires two enzymatic reactions. First, tyrosine hydroxylase (TH) converts tyrosine into DOP...

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On the Identity of DOPA Decarboxylase and 5-Hydroxytryptophan Decarboxylase

Cited by 199 publications

References 25 publications

Neurobiology of Pyridoxine

Neurobiology of Pyridoxine

Opposite sexual dimorphism of 3,4-dihydroxyphenylalanine decarboxylase in the kidney and small intestine of mice

A Biochemical and Functional Protein Complex Involving Dopamine Synthesis and Transport into Synaptic Vesicles

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