Role of glutamate decarboxylase-like protein 1 (GADL1) in taurine biosynthesis.

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Liu P, Ge X, Ding H, Jiang H, Christensen BM, Li J

Role of glutamate decarboxylase-like protein 1 (GADL1) in taurine biosynthesis.

J Biol Chem. 2012 Nov 30;287(49):40898-906. doi: 10.1074/jbc.M112.393728. Epub 2012 Oct 4.

PubMed ID

23038267 [ View in PubMed

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Abstract

This manuscript concerns the tissue-specific transcription of mouse and cattle glutamate decarboxylase-like protein 1 (GADL1) and the biochemical activities of human GADL1 recombinant protein. Bioinformatic analysis suggested that GADL1 appears late in evolution, only being found in reptiles, birds, and mammals. RT-PCR determined that GADL1 mRNA is transcribed at high levels in mouse and cattle skeletal muscles and also in mouse kidneys. Substrate screening determined that GADL1, unlike its name implies, has no detectable GAD activity, but it is able to efficiently catalyze decarboxylation of aspartate, cysteine sulfinic acid, and cysteic acid to beta-alanine, hypotaurine, and taurine, respectively. Western blot analysis verified the presence of GADL1 in mouse muscles, kidneys, C2C12 myoblasts, and C2C12 myotubes. Incubation of the supernatant of fresh muscle or kidney extracts with cysteine sulfinic acid resulted in the detection of hypotaurine or taurine in the reaction mixtures, suggesting the possible involvement of GADL1 in taurine biosynthesis. However, when the tissue samples were incubated with aspartate, no beta-alanine production was observed. We proposed several possibilities that might explain the inactivation of ADC activity of GADL1 in tissue protein extracts. Although beta-alanine-producing activity was not detected in the supernatant of tissue protein extracts, its potential role in beta-alanine synthesis cannot be excluded. There are several inhibitors of the ADC activity of GADL1 identified. The discovery of GADL1 biochemical activities, in conjunction with its expression and activities in muscles and kidneys, provides some tangible insight toward establishing its physiological function(s).

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pyridoxal phosphate	Glutamate decarboxylase-like protein 1	Protein	Humans	Unknown	Cofactor	Details

Polypeptides

Name	UniProt ID
Acidic amino acid decarboxylase GADL1	Q6ZQY3	Details