GADL1

Glutamate decarboxylase like 1 (GADL1) is the enzyme responsible for decarboxylating aspartate (Asp) to β-alanine and cysteine sulfinic acid (CSA) to hypotaurine.^[5] GADL1 is a Pyridoxal 5’-phosphate (PLP)-dependent enzyme. By decarboxylating Asp to β-alanine, GADL1 consequently plays a role in the production of carnosine.^[6] Carnosine and taurine have multiple biological functions such as calcium regulation, pH buffering, metal chelation, and antioxidant effects. β-Alanine also plays a role as neurotransmitter or neuromodulator in the central nervous system (CNS) and olfactory bulbs.^[7]

GADL1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2JIS
Identifiers
Aliases	GADL1, ADC, CSADC, HuADC, HuCSADC, glutamate decarboxylase like 1
External IDs	OMIM: 615601; MGI: 1920998; HomoloGene: 45812; GeneCards: GADL1; OMA:GADL1 - orthologs
EC number	4.1.1.29
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p24.1-p23 Start 30,726,197 bp[1] End 30,894,661 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 F3 Start 115,909,455 bp[2] End 116,076,176 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell germinal epithelium muscle of thigh deltoid muscle Skeletal muscle tissue of rectus abdominis gastrocnemius muscle gastric mucosa vastus lateralis muscle biceps brachii Descending thoracic aorta Top expressed in olfactory epithelium lumbar spinal ganglion knee joint vastus lateralis muscle soleus muscle triceps brachii muscle medial head of gastrocnemius muscle skeletal muscle tissue skin of external ear spermatid More reference expression data BioGPS n/a
Gene ontology Molecular function sulfinoalanine decarboxylase activity pyridoxal phosphate binding catalytic activity carboxy-lyase activity aspartate 1-decarboxylase activity lyase activity Cellular component cytosol Biological process cellular amino acid biosynthetic process carboxylic acid metabolic process sulfur amino acid catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 339896 73748 Ensembl ENSG00000144644 ENSMUSG00000056880 UniProt Q6ZQY3 Q80WP8 RefSeq (mRNA) NM_207359 NM_028638 RefSeq (protein) NP_997242 NP_082914 NP_001382689 Location (UCSC) Chr 3: 30.73 – 30.89 Mb Chr 9: 115.91 – 116.08 Mb PubMed search [3] [4]
Wikidata
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Homology with CSAD

GADL1 has 61% homology with another PLP-dependent enzyme cysteine sulfinic acid decarboxylase (CSAD).^[8] CSAD plays a role in taurine production by decarboxylating CSA to hypotaurine. Taurine is the most abundant amino acid in mammals and plays roles as an antioxidant, membrane stabilizer and neurotransmitter or neuromodulator in the CNS^[9] and recently has received growing attention as a biomarker for different diseases.^[10]

Tissue distribution

In humans, both GADL1 and CSAD are expressed in the brain and neurons whereas only CSAD was found in the liver. In mice, both enzymes are expressed in the brain, olfactory bulbs, and skeletal muscle but only CSAD was found in the kidney and liver.

GADL1 is named ADC, CSADC, HuADC, HuCSADC in some papers.

Structure

Both CSAD and GADL1 are homodimers. The structure of mouse GADL1 was published in 2018 with the PDB number 6ENZ ^[11] and the structure of mouse CSAD was published in 2021 with the PDB number 6ZEK.^[12]

Therapeutic potential

In 2014 a paper showed an association between GADL1 variants and bipolar patients' responses to lithium therapy.^[13] Although these findings were not replicable, this article triggers more studies on GADL1. So far there has not been any paper published reporting reproducible data on the therapeutic role of GADL1. However, this novel PLP-dependent enzyme has a high potential for further investigation.