tisdag 18 juni 2019

Tauriinin synteesin tärkeä entsyymi CSAD,cysteinisulfiinihappodekarboksylaasi on B6-vitamiinsita riippuvainen

cysteinesulfinic acid decarboxylase

 https://www.ncbi.nlm.nih.gov/pubmed/30131986


2018 Sep 19;9(9):4814-4821. doi: 10.1039/c8fo00740c.
The intervention effect of licorice in d-galactose induced aging rats by regulating the taurine metabolic pathway.

Abstract

Licorice, an edible and officinal plant material, has attracted considerable attention for its wide range of pharmacological activities. Our previous study showed that licorice can ameliorate cognitive damage and improve oxidative stress and apoptosis in aging rats induced by d-galactose (d-gal). In this study, in order to further explore the changes of the metabolic profile during the aging process and the antiaging mechanism of licorice, the 1H NMR-based metabolomics approach was used to analyze serum and urine samples and identify a potential biomarker in d-gal induced aging rats.

 The results revealed that the taurine metabolic pathway was significantly correlated with the ageing process in d-gal induced rats. Furthermore, the taurine contents were significantly decreased in both the serum and urine samples of aging rats compared with the controls. At the same time, the levels of
  •  cysteine dioxygenase type I (CDO1), 
  • cysteine sulfinic acid decarboxylase (CSAD) and
  •  glutamate decarboxylase type I (GAD1), 
which are the key enzymes affecting the synthesis reactions, were decreased in aging rats compared with the controls.
After licorice administration, the levels of taurine, CDO1 and CSAD were all significantly increased. These findings firstly demonstrated that the regulation of the taurine metabolic pathway is involved in the anti-aging effect of licorice in d-gal induced aging rats.
PMID: 30131986 DOI: 10.1039/c8fo00740c
[Indexed for MEDLINE]
Official Symbol CSAD
Official Full Name cysteine sulfinic acid decarboxylase 
 Gene type protein coding 
Also known as CSD; PCAP
 Summary: This gene encodes a member of the group 2 decarboxylase family. A similar protein in rodents plays a role in multiple biological processes as the rate-limiting enzyme in taurine biosynthesis, catalyzing the decarboxylation of cysteinesulfinate to hypotaurine. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011] Expression Ubiquitous expression in fat (RPKM 9.9), skin (RPKM 8.5) and 25 other tissues See more Orthologs mouse all
Preferred Names
cysteine sulfinic acid decarboxylase (CSAD)
Names
P-selectin cytoplasmic tail-associated protein (PCAP)
aspartate 1-decarboxylase  (ADC)
cysteine sulfinic acid decarboxylase-related protein
cysteine-sulfinate decarboxylase
sulfinoalanine decarboxylase
Conserved Domains (1) summary
cd06450
Location:89489
DOPA_deC_like; DOPA decarboxylase family. This family belongs to pyridoxal phosphate (PLP)-dependent aspartate aminotransferase superfamily (fold I). The major groups in this CD correspond to DOPA/tyrosine decarboxylase (DDC), histidine decarboxylase (HDC), and


Related articles in PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26327310
Abstract
Variants in the gene encoding the enzyme glutamic acid decarboxylase like 1 (GADL1) have been associated with response to lithium therapy. Both GADL1 and the related enzyme cysteine sulfinic acid decarboxylase (CSAD) have been proposed to be involved in the pyridoxal-5'-phosphate (PLP)-dependent biosynthesis of taurine.
 In the present study, we compared the catalytic properties, inhibitor sensitivity and expression profiles of GADL1 and CSAD in brain tissue.
 In mouse and human brain we observed distinct patterns of expression of the PLP-dependent decarboxylases CSAD, GADL1 and glutamic acid decarboxylase 67 (GAD67).
CSAD levels were highest during prenatal and early postnatal development;
 GADL1 peaked early in prenatal development,
 while GAD67 increased rapidly after birth.
Both CSAD and GADL1 are being expressed in neurons,
 whereas only CSAD mRNA was detected in astrocytes.
 Cysteine sulfinic acid was the preferred substrate for both mouse CSAD and GADL1, although both enzymes also decarboxylated cysteic acid and aspartate. In silico screening and molecular docking using the crystal structure of CSAD and in vitro assays led to the discovery of eight new enzyme inhibitors with partial selectivity for either CSAD or GADL1. Lithium had minimal effect on their enzyme activities.
 In conclusion, taurine biosynthesis in vertebrates involves two structurally related PLP-dependent decarboxylases (CSAD and GADL1) that have partially overlapping catalytic properties but different tissue distribution, indicating divergent physiological roles.
 Development of selective enzyme inhibitors targeting these enzymes is important to further dissect their (patho)physiological roles.
 

 

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