Biology:GADL1
 Generic protein structure example |
Glutamate decarboxylase like 1 (GADL1) is the enzyme responsible for decarboxylating aspartate (Asp) to β-alanine and cysteine sulfinic acid (CSA) to hypotaurine.[1] 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.[2] 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.[3]
Homology with CSAD
GADL1 has 61% homology with another PLP-dependent enzyme cysteine sulfinic acid decarboxylase (CSAD).[4] 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[5] and recently has received growing attention as a biomarker for different diseases.[6]
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 [7] and the structure of mouse CSAD was published in 2021 with the PDB number 6ZEK.[8]
Therapeutic potential
In 2014 a paper showed an association between GADL1 variants and bipolar patients' responses to lithium therapy.[9] 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.
References
- ↑ "Role of glutamate decarboxylase-like protein 1 (GADL1) in taurine biosynthesis". The Journal of Biological Chemistry 287 (49): 40898–906. November 2012. doi:10.1074/jbc.M112.393728. PMID 23038267.
- ↑ "GADL1 is a multifunctional decarboxylase with tissue-specific roles in β-alanine and carnosine production". Science Advances 6 (29): eabb3713. July 2020. doi:10.1126/sciadv.abb3713. PMID 32733999. Bibcode: 2020SciA....6.3713M.
- ↑ "Physiology and pathophysiology of carnosine". Physiological Reviews 93 (4): 1803–45. October 2013. doi:10.1152/physrev.00039.2012. PMID 24137022.
- ↑ "Mammalian CSAD and GADL1 have distinct biochemical properties and patterns of brain expression". Neurochemistry International 90: 173–84. November 2015. doi:10.1016/j.neuint.2015.08.013. PMID 26327310.
- ↑ "Review: taurine: a "very essential" amino acid". Molecular Vision 18: 2673–86. 2012. PMID 23170060.
- ↑ "Taurine and glutathione levels in plasma before and after ECT treatment". Psychiatry Research 198 (1): 53–7. June 2012. doi:10.1016/j.psychres.2012.02.016. PMID 22453189.
- ↑ "Structure of the mouse acidic amino acid decarboxylase GADL1". Acta Crystallographica. Section F, Structural Biology Communications 74 (Pt 1): 65–73. January 2018. doi:10.1107/S2053230X17017848. PMID 29372909. PMC 5947694. http://scripts.iucr.org/cgi-bin/paper?S2053230X17017848.
- ↑ "Structure and substrate specificity determinants of the taurine biosynthetic enzyme cysteine sulphinic acid decarboxylase". Journal of Structural Biology 213 (1): 107674. March 2021. doi:10.1016/j.jsb.2020.107674. PMID 33253877.
- ↑ "Variant GADL1 and response to lithium therapy in bipolar I disorder". The New England Journal of Medicine 370 (2): 119–28. January 2014. doi:10.1056/NEJMoa1212444. PMID 24369049.
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