Substrate specificity and other properties of DOPA decarboxylase from guinea pig kidneys

Srinivasan, Karthik K.; Awapara, Jörge

doi:10.1016/0005-2744(78)90150-x

Cited by 54 publications

(29 citation statements)

References 19 publications

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“…Mammalian DDC has been the most extensively studied AAAD in terms of substrate specificity and catalytic reactions. Based on literature, mammalian DDC can use both DOPA and 5-HTP as substrates (24,25), but the plant AAADs or AASs use aromatic amino acids with either the indole ring or benzene ring, but never both (1,8,9). Other than its typical decarboxylation activity to DOPA and 5-HTP, mammalian DDC can also catalyze oxidative deamination of dopamine and 5-HT (26,27).…”

Section: Discussionmentioning

confidence: 99%

Biochemical Evaluation of the Decarboxylation and Decarboxylation-Deamination Activities of Plant Aromatic Amino Acid Decarboxylases

Torrens-Spence

Liu

Ding

et al. 2013

Journal of Biological Chemistry

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Background: Plant arylalkylamine and aldehyde synthesizing aromatic amino acid decarboxylases (AAAD) are effectively indistinguishable. Results: Mutagenesis of a single AAAD residue enables the interconversion of activities. Conclusion: A single residue is primarily responsible for differentiating plant AAAD decarboxylase and aldehyde synthase activities. Significance: AAAD activity differentiation enables primary sequence activity identification, generation of unusual AAAD enzyme products, and AAAD mechanistic insights.

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Section: Discussionmentioning

confidence: 99%

Biochemical Evaluation of the Decarboxylation and Decarboxylation-Deamination Activities of Plant Aromatic Amino Acid Decarboxylases

Torrens-Spence

Liu

Ding

et al. 2013

Journal of Biological Chemistry

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“…The enzymes necessary to synthesize dopamine are found in the kidney (9); aromatic L-amino acid decarboxylase, which converts L-DOPA to dopamine, seems to be mainly located around the apical cell membrane (5) ofthe S 1 and S2 segments of the renal proximal tubule (10). Dopamine produced in the proximal convoluted tubule (PCT)1 (1,5,10,11) Receivedfor publication 12 April 1989 and in revisedform 10 July 1989.…”

Section: Introductionmentioning

confidence: 99%

Defective dopamine-1 receptor adenylate cyclase coupling in the proximal convoluted tubule from the spontaneously hypertensive rat.

Kinoshita¹,

Sidhu²,

Felder³

1989

J. Clin. Invest.

145

114

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The natriuretic effect of DA-1 agonists is less in the spontaneously hypertensive rat (SHR) than its normotensive control, the Wistar-Kyoto rat (WKY). To determine a mechanism of the decreased effect of DA-1 agonists on sodium transport, DA-1 receptors in renal proximal convoluted tubule (PCI) were studied by radioligand binding and by adenylate cyclase (AC) determinations. Specific binding of '25I-SCH 23982 (defined by 10 MM SCH 23390, a DA-1 antagonist) was concentration dependent, saturable, and stereoselective. The dissociation constant, maximum receptor density, and DA-1 antagonist inhibition constant were similar in SHR and WKY. The apparent molecular weight of the DA-1 receptor determined by the photoaffinity D1 probe '25I-MAB was also similar in WKY and SHR. However, DA-1 agonists competed more effectively for specific '25I-SCH 23982 binding sites in WKY than in SHR.Basal as well as forskolin, parathyroid hormone, GTP and Gpp(NH)p-stimulated-AC activities were similar. In contrast DA-1 agonists (fenoldopam, SKF 38393, SND 911C12) stimulated AC activity to a lesser extent in SHR. GTP and Gpp(NH)p enhanced the ability of DA-1 agonists to stimulate AC activity in WKY but not in SHR. These data suggest a defect in the DA-1 receptor-second messenger coupling mechanism in the PCI of the SHR.

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“…Tyrosine positional isomers, ortho-and meta-tyrosine, are good candidates since both are excellent AAAD substrates [e.g., Srinivasan and Awapara, 1978] and their noncatecholic structure makes them poor COMT substrates [DeJesus et al, 1989]. Although their physiologic significance has yet to be determined, both ortho-and meta-tyrosine are found in trace amounts in human plasma [Ishimitsu et al, 1986].…”

mentioning

confidence: 99%

“…Another noncatecholic L-DOPA analog, orthotyrosine, like L-DOPA and m-tyrosine, is a good AAAD substrate [e.g., Srinivasan and Awapara, 1978]. Fluorinated and brominated o-tyrosine analogs have been prepared as possible PET tracers for AAAD .…”

mentioning

confidence: 99%

Positron‐labeled DOPA analogs to image dopamine terminals

DeJesus

2003

Drug Development Research

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Altered dopamine function has been implicated in disorders such as Parkinson's disease (PD) and other motor disorders, schizophrenia, substance abuse, attention deficit disorder, and other neuropsychiatric diseases. A useful approach to the development of PET imaging agents for dopamine terminals is to target the enzymes involved in dopamine biosynthesis. Tyrosine hydroxylase (TH) converts dietary L-p-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA), which is the first and rate-limiting step in dopamine synthesis. Thus, a TH-targeted imaging agent would be the ideal PET tracer of dopamine neuronal activity. However, efforts to develop TH-based tracers have so far been unsuccessful. The next enzyme in dopamine synthesis is aromatic L-amino acid decarboxylase (AAAD), which converts L-DOPA to dopamine. AAAD was the first target in the development of imaging agents for dopamine neurons. The first useful AAAD PET tracer was 6-[ F]Fluoro-L-DOPA (FDOPA). Later, a practicable synthesis of L-[b-11 C]DOPA was developed. However, the adherence of these tracers to all the catabolic pathways of L-DOPA has been a disadvantage because of the contributions of labeled metabolites to PET images. Thus, alternative tracers with simpler metabolism such as fluoro-L-m-tyrosine (FMT) have been developed. PET studies in nonhuman primates have suggested that FMT is the PET imaging agent of choice for AAADcontaining neurons. Initial human studies show that this marker is useful in the assessment of AAADrelated neuropsychiatric disorders. This article discusses the origins and validation of dopamine PET tracers and delineates the similarities and differences between therapeutic drug development and radiopharmaceutical development as exemplified by studies on the dopamine system. Drug Dev. Res.

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Substrate specificity and other properties of DOPA decarboxylase from guinea pig kidneys

Cited by 54 publications

References 19 publications

Biochemical Evaluation of the Decarboxylation and Decarboxylation-Deamination Activities of Plant Aromatic Amino Acid Decarboxylases

Biochemical Evaluation of the Decarboxylation and Decarboxylation-Deamination Activities of Plant Aromatic Amino Acid Decarboxylases

Defective dopamine-1 receptor adenylate cyclase coupling in the proximal convoluted tubule from the spontaneously hypertensive rat.

Positron‐labeled DOPA analogs to image dopamine terminals

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