Role of Glutamate Decarboxylase-like Protein 1 (GADL1) in Taurine Biosynthesis

Liu, Pingyang; Ge, Xiaomei; Ding, Huanjun; Jiang, Honglin; Christensen, Bruce M.; Li, Jianyong

doi:10.1074/jbc.m112.393728

Cited by 44 publications

(53 citation statements)

References 46 publications

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“…The motif we identified is also germane to recent reports on the specific CSA decarboxylase activity of an enzyme from Aedes aegypti, aspartate 1-decarboxylase ( Ae ADC) and the of the human glutamic acid decarboxylase-like protein 1 (hGADL1) which was shown to display significant CSA decarboxylase activity (32, 33). Interestingly, the Ae ADC sequence contains the consensus CSAD recognition motif (F 1 aa 19 S 2 aaY 3 ), while hGADL1 has a very similar recognition motif (Y 1 aa 19 S 2 aaY 3 ), differing from CSAD only at the R 1 position.…”

Section: Discussionsupporting

confidence: 75%

Discovery of a Substrate Selectivity Motif in Amino Acid Decarboxylases Unveils a Taurine Biosynthesis Pathway in Prokaryotes

et al. 2013

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Taurine, the most abundant free amino acid in mammals, with many critical roles such as neuronal development, had so far only been reported to be synthetized in eukaryotes. Taurine is the major product of cysteine metabolism in mammals, and its biosynthetic pathway consists of cysteine dioxygenase and cysteine sulfinic acid decarboxylase (hCSAD). Sequence, structural, and mutational analyses of the structurally and sequentially related hCSAD and human glutamic acid decarboxylase (hGAD) enzymes revealed a three residue substrate recognition motif (X1aa19X2aaX3), within the active site that is responsible for coordinating their respective preferred amino acid substrates. Introduction of the cysteine sulfinic acid (CSA) motif into hGAD (hGAD-S192F/N212S/F214Y) resulted in an enzyme with a >700 fold switch in selectivity towards the decarboxylation of CSA over its preferred substrate, L-glutamic acid. Surprisingly, we found this CSA recognition motif in the genome sequences of several marine bacteria, prompting us to evaluate the catalytic properties of bacterial amino acid decarboxylases that were predicted by sequence motif to decarboxylate CSA but had been annotated as GAD enzymes. We show that CSAD from Synechococcus sp. PCC 7335 specifically decarboxylated CSA and that the bacteria accumulated intracellular taurine. The fact that CSAD homologues exist in certain bacteria and are frequently found in operons containing the recently discovered bacterial cysteine dioxygenases that oxidize L-cysteine to CSA, supports the idea that a bona fide bacterial taurine biosynthetic pathway exists in prokaryotes.

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Section: Discussionsupporting

confidence: 75%

Discovery of a Substrate Selectivity Motif in Amino Acid Decarboxylases Unveils a Taurine Biosynthesis Pathway in Prokaryotes

et al. 2013

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“…In the Wnt pathway, the main target of GSK-3 is a protein called β-catenin (Gould et al, 2004a). GSK-3 is a part of a destruction complex that phosphorylates β-catenin and this leads to β-catenin’s degradation (Clevers and Nusse, 2012; Liu et al, 2012). Activation of the Wnt pathway inhibits GSK-3, blocking degradation of β-catenin and resulting in increased β-catenin-driven gene expression (see (Huang and Klein, 2004; Logan and Nusse, 2004) for review).…”

Section: Lithium and Gsk-3mentioning

confidence: 99%

“…Sequencing identified a 1-base deletion in high linkage disequilibrium with these SNPs, which may have alternative splicing effects on GADL1 (Chen et al, 2014). It is difficult to predict the possible underlying mechanisms leading to this association since the function of GADL1 in the nervous system is not currently known (Liu et al, 2012). However, it has sequence similarities with glutamate decarboxylase (GAD) isoforms, the enzyme that catalyzes the glutamate to GABA conversion and is essential for proper functioning of GABAergic synaptic neurotransmission (Liu et al, 2012).…”

Section: Neurotransmitter Systems and Lithiummentioning

confidence: 99%

“…It is difficult to predict the possible underlying mechanisms leading to this association since the function of GADL1 in the nervous system is not currently known (Liu et al, 2012). However, it has sequence similarities with glutamate decarboxylase (GAD) isoforms, the enzyme that catalyzes the glutamate to GABA conversion and is essential for proper functioning of GABAergic synaptic neurotransmission (Liu et al, 2012). While an association between these SNPs and lithium therapy response was identified in three cohorts, it should be kept in mind that this study was conducted in an ethnically homogenous population sample (Han Chinese).…”

Section: Neurotransmitter Systems and Lithiummentioning

confidence: 99%

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Molecular actions and clinical pharmacogenetics of lithium therapy

Can

Schulze

Gould

2014

Pharmacology Biochemistry and Behavior

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Mood disorders, including bipolar disorder and depression, are relatively common human diseases for which pharmacological treatment options are often not optimal. Among existing pharmacological agents and mood stabilizers used for the treatment of mood disorders, lithium has a unique clinical profile. Lithium has efficacy in the treatment of bipolar disorder generally, and in particular mania, while also being useful in the adjunct treatment of refractory depression. In addition to antimanic and adjunct antidepressant efficacy, lithium is also proven effective in the reduction of suicide and suicidal behaviors. However, only a subset of patients manifests beneficial responses to lithium therapy and the underlying genetic factors of response are not exactly known. Here we discuss preclinical research suggesting mechanisms likely to underlie lithium’s therapeutic actions including direct targets inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) among others, as well as indirect actions including modulation of neurotrophic and neurotransmitter systems and circadian function. We follow with a discussion of current knowledge related to the pharmacogenetic underpinnings of effective lithium therapy in patients within this context. Progress in elucidation of genetic factors that may be involved in human response to lithium pharmacology has been slow, and there is still limited conclusive evidence for the role of a particular genetic factor. However, the development of new approaches such as genome-wide association studies (GWAS), and increased use of genetic testing and improved identification of mood disorder patients sub-groups will lead to improved elucidation of relevant genetic factors in the future.

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“…Recently, glutamate decarboxylase-like proteins (GAD) from insects (42) and humans (43), which also belong to the class II decarboxylase family, were reported to function as aspartate decarboxylases to produce ␤-alanine. Specifically, GAD2 from mosquitoes was found to exclusively function in the production of ␤-alanine (42).…”

Section: Discussionmentioning

confidence: 99%

β-Alanine Biosynthesis in Methanocaldococcus jannaschii

Wang

White

2014

J Bacteriol

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One efficient approach to assigning function to unannotated genes is to establish the enzymes that are missing in known biosynthetic pathways. One group of such pathways is those involved in coenzyme biosynthesis. In the case of the methanogenic archaeon Methanocaldococcus jannaschii as well as most methanogens, none of the expected enzymes for the biosynthesis of the ␤-alanine and pantoic acid moieties required for coenzyme A are annotated. To identify the gene(s) for ␤-alanine biosynthesis, we have established the pathway for the formation of ␤-alanine in this organism after experimentally eliminating other known and proposed pathways to ␤-alanine from malonate semialdehyde, L-alanine, spermine, dihydrouracil, and acryloyl-coenzyme A (CoA). Our data showed that the decarboxylation of aspartate was the only source of ␤-alanine in cell extracts of M. jannaschii. Unlike other prokaryotes where the enzyme producing ␤-alanine from L-aspartate is a pyruvoyl-containing L-aspartate decarboxylase (PanD), the enzyme in M. jannaschii is a pyridoxal phosphate (PLP)-dependent L-aspartate decarboxylase encoded by MJ0050, the same enzyme that was found to decarboxylate tyrosine for methanofuran biosynthesis. A K m of ϳ0.80 mM for L-aspartate with a specific activity of 0.09 mol min ؊1 mg ؊1 at 70°C for the decarboxylation of L-aspartate was measured for the recombinant enzyme. The MJ0050 gene was also demonstrated to complement the Escherichia coli panD deletion mutant cells, in which panD encoding aspartate decarboxylase in E. coli had been knocked out, thus confirming the function of this gene in vivo.

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Role of Glutamate Decarboxylase-like Protein 1 (GADL1) in Taurine Biosynthesis

Cited by 44 publications

References 46 publications

Discovery of a Substrate Selectivity Motif in Amino Acid Decarboxylases Unveils a Taurine Biosynthesis Pathway in Prokaryotes

Discovery of a Substrate Selectivity Motif in Amino Acid Decarboxylases Unveils a Taurine Biosynthesis Pathway in Prokaryotes

Molecular actions and clinical pharmacogenetics of lithium therapy

β-Alanine Biosynthesis in Methanocaldococcus jannaschii

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