onsdag 19 juni 2019
L-cysteiiniä proteiinisynteesiin eikä D-cysteiiniä
https://www.ncbi.nlm.nih.gov/pubmed/9609386
Chem Biol Interact. 1998 Apr 3;110(3):189-202.
The glutathione dependence of inorganic sulfate formation from L- or D-cysteine in isolated rat hepatocytes.Abstract
The GSH dependence of the metabolic pathways involved in the conversion of cysteine to sulfate in intact cells has been investigated. It was found that hepatocyte-catalysed sulfate formation from added L-cysteine
did not occur if hepatocyte GSH was depleted beforehand, but was
restored when GSH levels recovered.
Furthermore, sulfate formation did not recover in GSH-depleted hepatocytes if GSH synthesis was prevented with buthionine sulfoximine.
Thiosulfate formation was, however, markedly enhanced in GSH-depleted hepatocytes.
These results suggest that thiosulfate is an intermediate in the formation of inorganic sulfate from L-cysteine and that GSH was required for the conversion of thiosulfate to inorganic sulfate.
Much less sulfate was formed if the cysteine (Cys) was replaced with cysteinesulfinate (CSA)
Furthermore, sulfate formation from L-cysteine was markedly inhibited by the addition of the transaminase inhibitor DL-cycloserine or the gamma-cystathionase inhibitor DL-propargylglycine.
The major routes of sulfate formation from L-cysteine therefore seems to involve pathways that do not involve L-cysteinesulfinate.
Similar amounts of sulfate were formed from D-cysteine as L-cysteine.
Thiosulfate instead of sulfate was also formed in GSH-depleted hepatocytes.
However, sulfate formation from D-cysteine differed from L-cysteine in that it was inhibited by the D-aminoacid oxidase inhibitor sodium benzoate and was not affected by transaminase or gamma-cystathionase inhibitors.
These results suggest that thiosulfate is an intermediate in sulfate formation from D-cysteine and involves the oxidation of D-cysteine by D-amino acid oxidase to form beta-mercaptopyruvate.
Furthermore, sulfate formation did not recover in GSH-depleted hepatocytes if GSH synthesis was prevented with buthionine sulfoximine.
Thiosulfate formation was, however, markedly enhanced in GSH-depleted hepatocytes.
These results suggest that thiosulfate is an intermediate in the formation of inorganic sulfate from L-cysteine and that GSH was required for the conversion of thiosulfate to inorganic sulfate.
Much less sulfate was formed if the cysteine (Cys) was replaced with cysteinesulfinate (CSA)
Furthermore, sulfate formation from L-cysteine was markedly inhibited by the addition of the transaminase inhibitor DL-cycloserine or the gamma-cystathionase inhibitor DL-propargylglycine.
The major routes of sulfate formation from L-cysteine therefore seems to involve pathways that do not involve L-cysteinesulfinate.
Similar amounts of sulfate were formed from D-cysteine as L-cysteine.
Thiosulfate instead of sulfate was also formed in GSH-depleted hepatocytes.
However, sulfate formation from D-cysteine differed from L-cysteine in that it was inhibited by the D-aminoacid oxidase inhibitor sodium benzoate and was not affected by transaminase or gamma-cystathionase inhibitors.
These results suggest that thiosulfate is an intermediate in sulfate formation from D-cysteine and involves the oxidation of D-cysteine by D-amino acid oxidase to form beta-mercaptopyruvate.
- PMID:
- 9609386
- [Indexed for MEDLINE]
H2S merkityksestä mm. sirtuiinien signalointitiessä
https://www.ncbi.nlm.nih.gov/pubmed/30274149
Antioxidants (Basel). 2018 Sep 28;7(10). pii: E129. doi: 10.3390/antiox7100129.
Role of Hydrogen Sulfide in NRF2- and Sirtuin-Dependent Maintenance of Cellular Redox Balance. Corsello T1, Komaravelli N2, Casola A3,4.
Vetysulfidista (H2S) on tullut kriittinen gasatransmitteri signaloiva molekyyli, joka moduloi solun biologisia tapahtumia, joilla niillä on merkityst sydämen, aivojen, maksan, verisuoniston taudeissa ja immuunivasteissa.
Abstract Hydrogen sulfide (H₂S) has arisen as a critical gasotransmitter signaling molecule modulating cellular biological events related to health and diseases in heart, brain, liver, vascular systems and immune response.
Vetysulfidin endogeenista tuotantoa välittää kolme entsyymiä:
Cystationin beetasyntaasi (CBS),
cystationin gamma-lyaasi (GSE) ja
3-merkapto-palorypälehapon sulfustransferaasi (3-MST).
Näistä entsyymit CBS ja CSE sijoittuvat orgaanispesifissti. Entsyymi 3-MST on mitokondriaalinen ja sytosolinen entsyymi.
Cystationin beetasyntaasi (CBS),
cystationin gamma-lyaasi (GSE) ja
3-merkapto-palorypälehapon sulfustransferaasi (3-MST).
Näistä entsyymit CBS ja CSE sijoittuvat orgaanispesifissti. Entsyymi 3-MST on mitokondriaalinen ja sytosolinen entsyymi.
- Three enzymes mediate the endogenous production of H₂S:
- cystathione β-synthase (CBS),
- cystathione γ-lyase (CSE) and
- 3-mercaptopyruvate sulfurtransferase (3-MST).
- CBS and CSE localizations are organ-specific.
- 3-MST is a mitochondrial and cytosolic enzyme.
- The generation of H₂S is firmly regulated by these enzymes under normal physiological conditions. Recent studies have highlighted the role of H₂S in cellular redox homeostasis, as it displays significant antioxidant properties. H₂S exerts antioxidant effects through several mechanisms, such as quenching reactive oxygen species (ROS) and reactive nitrogen species (RNS), by modulating cellular levels of glutathione (GSH) and thioredoxin (Trx-1) or increasing expression of antioxidant enzymes (AOE), by activating the transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2).
- H₂S also influences the activity of the histone deacetylase protein family of sirtuins, which plays an important role in inhibiting oxidative stress in cardiomyocytes and during the aging process by modulating AOE gene expression. This review focuses on the role of H₂S in NRF2 and sirtuin signaling pathways as they are related to cellular redox homeostasis.
KEYWORDS: NRF2; hydrogen sulfide; oxidative stress; redox; sirtuin
(1) Cysteiiniaminohaposta kohti tauriinin tai sulfaatin muodostusta cys-dioxygenaasilla CDO1, joka tekee cysteiinisulfiinihappoa.
Entsyymi cysteiinidioxygenaasi CDO1 (5q22.3) on primäärinen cysteiiniä metaboloiva entsyymi ja tuote on kysteiinisulfiinihappoa CSAD.
(Tämä CDO1 entsyymi on säätelyllinen alkukohta sulfaatin muodostuksessa. Sulfaattia tarvitaan detoksikaatiojärjestelmään ja erilaisten rikkiä sisältävien kehomolekyylien luomiseen. Sulfotransferaaseja ja arylsulfataasientsyymejä taas avustaa kofaktorina k-vitamiini ja B6 vitamiini)
CDO1 Cystein dioxygenase 1https://www.ncbi.nlm.nih.gov/gene/1036
- Official Symbol CDO1
- Official Full Name cysteine dioxygenase type 1provided by HGNC
- Also known as CDO-I
- Expression Biased expression in liver (RPKM 94.6), fat (RPKM 66.8) and 8 other tissues See more
- Orthologs mouse all
- Methylated promoter DNA of CDO1 gene and preoperative serum CA19-9 are prognostic biomarkers in primary extrahepatic cholangiocarcinoma. Nakamoto S, et al. PLoS One, 2018. PMID 30325974, Free PMC Article
- Epigenetic Status of CDO1 Gene May Reflect Chemosensitivity in Colon Cancer with Postoperative Adjuvant Chemotherapy. Yokoi K, et al. Ann Surg Oncol, 2019 Feb. PMID 30311169
- Cysteine dioxygenase type 1 (CDO1) gene promoter methylation during the adenoma-carcinoma sequence in colorectal cancer. Kojima K, et al. PLoS One, 2018. PMID 29746493, Free PMC Article
- Prognostic significance of promoter DNA hypermethylation of the cysteine dioxygenase 1 (CDO1) gene in primary gallbladder cancer and gallbladder disease. Igarashi K, et al. PLoS One, 2017. PMID 29161283, Free PMC Article
- The clinical significance of cysteine dioxygenase type 1 methylation in Barrett esophagus adenocarcinoma. Kojima K, et al. Dis Esophagus, 2017 Mar 1. PMID 28184414
GeneRIFs: Gene References Into Functions
- High expression of CDO1 gene increased chemoresistance in Colon Cancer.
- In the present study, we compared the 2 potential epigenetic prognostic markers of CDO1 hypermethylation and HOPX hypermethylation using the same breast cancer samples, and the final focus was given on CDO1 hypermethylation
- CDO1 hypermethylation, preoperative serum CA19-9 and perineural invasion were independent prognostic factors in primary extrahepatic cholangiocarcinoma
- High CDO1 methylation is associated with colorectal cancer progression.
- Promoter NA methylation of CDO1 was demonstrated for the first time to be a cancer-associated methylation in primary gallbladder cancer(GBC), and it has the potential to be a prognostic biomarker of GBC for high-risk patients with stage II GBC.
- CDO1 methylation could be a potent prognostic predictor in primary esophageal squamous cell carcinoma and have great potential as a prognostic factor to guide the treatment of patients who need adjuvant chemotherapy.
- High methylation of CDO1 gene is responsible of the development of the esophageal adenocarcinoma.
- CDO1 promoter methylation is involved in gene regulation and is a potential prognostic biomarker for BCR-free survival in prostate cancer (PC) patients following radical prostatectomy. Further studies are needed to validate CDO1 methylation assays and to evaluate the clinical utility of CDO1 methylation for the management of PCa
- methylation of the CDO1 gene promoter could be strong prognostic indicator in primary BC without preoperative treatment.
- CDO1 promoter methylation may not substitute common prognostic makers to predict ccRCC survival, but offers additional, relevant prognostic information, indicating that it might be a novel molecular marker to determine ccRCC prognosis
The protein CDO1 https://www.ncbi.nlm.nih.gov/protein/NP_001310494.1
LOCUS NP_001310494 219 aa linear PRI 01-JUN-2019 DEFINITION cysteine dioxygenase type 1 isoform 1 [Homo sapiens]. ACCESSION NP_001310494 VERSION NP_001310494.1 DBSOURCE REFSEQ: accession NM_001323565.2 KEYWORDS RefSeq. SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (residues 1 to 219) AUTHORS Tanaka Y, Kosaka Y, Waraya M, Yokota K, Harada H, Kaida T, Kikuchi M, Minatani N, Nishimiya H, Katoh H, Sengoku N, Watanabe M and Yamashita K. TITLE Differential Prognostic Relevance of Promoter DNA Methylation of CDO1 and HOPX in Primary Breast Cancer JOURNAL Anticancer Res. 39 (5), 2289-2298 (2019) PUBMED 31092420 REMARK GeneRIF: In the present study, we compared the 2 potential epigenetic prognostic markers of CDO1 hypermethylation and HOPX hypermethylation using the same breast cancer samples, and the final focus was given on CDO1 hypermethylation REFERENCE 2 (residues 1 to 219) AUTHORS Yokoi K, Harada H, Yokota K, Ishii S, Tanaka T, Nishizawa N, Shimazu M, Kojo K, Miura H, Yamanashi T, Sato T, Nakamura T, Watanabe M and Yamashita K. TITLE Epigenetic Status of CDO1 Gene May Reflect Chemosensitivity in Colon Cancer with Postoperative Adjuvant Chemotherapy JOURNAL Ann. Surg. Oncol. 26 (2), 406-414 (2019) PUBMED 30311169 REMARK GeneRIF: High expression of CDO1 gene increased chemoresistance in Colon Cancer. REFERENCE 3 (residues 1 to 219) AUTHORS Nakamoto S, Kumamoto Y, Igarashi K, Fujiyama Y, Nishizawa N, Ei S, Tajima H, Kaizu T, Watanabe M and Yamashita K. TITLE Methylated promoter DNA of CDO1 gene and preoperative serum CA19-9 are prognostic biomarkers in primary extrahepatic cholangiocarcinoma JOURNAL PLoS ONE 13 (10), e0205864 (2018) PUBMED 30325974 REMARK GeneRIF: CDO1 hypermethylation, preoperative serum CA19-9 and perineural invasion were independent prognostic factors in primary extrahepatic cholangiocarcinoma Publication Status: Online-Only REFERENCE 4 (residues 1 to 219) AUTHORS Kojima K, Nakamura T, Ohbu M, Katoh H, Ooizumi Y, Igarashi K, Ishii S, Tanaka T, Yokoi K, Nishizawa N, Yokota K, Kosaka Y, Sato T, Watanabe M and Yamashita K. TITLE Cysteine dioxygenase type 1 (CDO1) gene promoter methylation during the adenoma-carcinoma sequence in colorectal cancer JOURNAL PLoS ONE 13 (5), e0194785 (2018) PUBMED 29746493 REMARK GeneRIF: High CDO1 methylation is associated with colorectal cancer progression. Publication Status: Online-Only REFERENCE 5 (residues 1 to 219) AUTHORS Igarashi K, Yamashita K, Katoh H, Kojima K, Ooizumi Y, Nishizawa N, Nishiyama R, Kawamata H, Tajima H, Kaizu T, Kumamoto Y and Watanabe M. TITLE Prognostic significance of promoter DNA hypermethylation of the cysteine dioxygenase 1 (CDO1) gene in primary gallbladder cancer and gallbladder disease JOURNAL PLoS ONE 12 (11), e0188178 (2017) PUBMED 29161283 REMARK GeneRIF: Promoter NA methylation of CDO1 was demonstrated for the first time to be a cancer-associated methylation in primary gallbladder cancer(GBC), and it has the potential to be a prognostic biomarker of GBC for high-risk patients with stage II GBC. Publication Status: Online-Only REFERENCE 6 (residues 1 to 219) AUTHORS Harrington JJ, Sherf B, Rundlett S, Jackson PD, Perry R, Cain S, Leventhal C, Thornton M, Ramachandran R, Whittington J, Lerner L, Costanzo D, McElligott K, Boozer S, Mays R, Smith E, Veloso N, Klika A, Hess J, Cothren K, Lo K, Offenbacher J, Danzig J and Ducar M. TITLE Creation of genome-wide protein expression libraries using random activation of gene expression JOURNAL Nat. Biotechnol. 19 (5), 440-445 (2001) PUBMED 11329013 REFERENCE 7 (residues 1 to 219) AUTHORS Qusti S, Parsons RB, Abouglila KD, Waring RH, Williams AC and Ramsden DB. TITLE Development of an in vitro model for cysteine dioxygenase expression in the brain JOURNAL Cell Biol. Toxicol. 16 (4), 243-255 (2000) PUBMED 11101006 The development of an in vitro model for cysteine dioxygenase (CDO) expression in the brain would provide a useful model for determining the mechanisms for the regulation of CDO expression that does not involve the use of animals. Here we demonstrate the screening and characterization of a cell line that expresses CDO, the primary metabolizing enzyme of cysteine and the regulatory point of sulfate production. A panel of four commercially available tumor-derived human brain cell lines, each representing one major class of brain cell, were screened using western blotting and activity assay for cysteine dioxygenase expression. One cell line, TE 671 (human medulloblastoma) was found to express both a protein of approximately 70 kDa and CDO activity. Nuclease protection assay (NPA) of mRNA isolated from TE 671 showed the expression of a CDO mRNA. Reverse transcription-polymerase chain reaction of this mRNA and sequencing of the cDNA obtained showed that this was indeed CDO. Treatment of TE 671 cells with cysteine resulted in the upregulation of CDO mRNA, whereas treatment with tumor necrosis factor alpha resulted in the downregulation of CDO mRNA, as evidenced using NPA. The characterization of an in vitro model for CDO expression provides a useful tool for the investigation of this important enzyme, which may have an etiological role in the pathogenesis of Parkinson's disease. REFERENCE 8 (residues 1 to 219) AUTHORS Ramsden DB, Kapadi A, Fitch NJ, Farmer MJ, Bennett P and Williams AC. TITLE Human cysteine dioxygenase type I (CDO-I; EC 1.13.11.20): 5' flanking region and intron-exon structure of the gene JOURNAL MP, Mol. Pathol. 50 (5), 269-271 (1997) PUBMED 9497919 REFERENCE 9 (residues 1 to 219) AUTHORS Jeremiah S, McCann KP, Williams AC, Ramsden DB, Pilz AJ, Fox MF and Povey S. TITLE Chromosomal localisation of genes coding for human and mouse liver cytosolic cysteine dioxygenase JOURNAL Ann. Hum. Genet. 60 (1), 29-33 (1996) PUBMED 8835096 REFERENCE 10 (residues 1 to 219) AUTHORS McCann KP, Akbari MT, Williams AC and Ramsden DB. TITLE Human cysteine dioxygenase type I: primary structure derived from base sequencing of cDNA JOURNAL Biochim. Biophys. Acta 1209 (1), 107-110 (1994) PUBMED 7524679 COMMENT VALIDATED REFSEQ: This record has undergone validation or preliminary review. The reference sequence was derived from AC026449.6, DA849625.1, AK130357.1 and BC024241.2. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR5189664.60540.1, SRR1803613.237389.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA2467146, SAMEA2467147 [ECO:0000348] ##Evidence-Data-END## FEATURES Location/Qualifiers source 1..219 /organism="Homo sapiens" /db_xref="taxon:9606" /chromosome="5" /map="5q22.3" Protein 1..219 /product="cysteine dioxygenase type 1 isoform 1" /EC_number="1.13.11.20" /note="cysteine dioxygenase, type I" /calculated_mol_wt=24700 CDS 1..219 /gene="CDO1" /gene_synonym="CDO-I" /coded_by="NM_001323565.2:263..922" /note="isoform 1 is encoded by transcript variant 1" /db_xref="GeneID:1036" /db_xref="HGNC:HGNC:1795" /db_xref="MIM:603943" ORIGIN 1 meqtevlkpr tladlirilh qlfagdevnv eevqaimeay esdptewamy akfdqysrgr 61 glqfvvgggs gggwlwytrn lvdqgngkfn lmilcwgegh gssihdhtns hcflkmlqgn 121 lketlfawpd kksnemvkks ervlrenqca yindsiglhr venishtepa vslhlysppf 181 dtchafdqrt ghknkvtmtf hskfgirtpn atsgslenn //
- Seuraaksi CSAD- molekyylistä cysteinsulphinic acid , kysteiinisulfiinihappo.
tisdag 18 juni 2019
Hyvin metioniinipitoinen dieetti
Näissä listoissa metioniinipitoisista ruoista eistetään asia lähinnä proteiinipitoisuuden kohttomaistarkoituksessa, muta samasta tiedosta voi myös käsittää, minkälaisisen proteiinien nauttimisessa tulee tavoitella kohtuullisuutta, että metioniinirasite ei tule liian suureksipainokiloa kohden, sillä aineenvaihdunnassa muodostuu sitten kertymåä Hcy:stä, joka voi päästä hakoteille kertymisvaiheestaan.
https://www.myfooddata.com/articles/high-methionine-foods.php
High methionine foods include
nuts,
beef,
lamb,
cheese,
turkey,
pork,
fish,
shellfish,
soy,
eggs,
dairy, and
beans.
https://www.myfooddata.com/articles/high-methionine-foods.php#methionine-rich-foods
https://www.myfooddata.com/articles/high-methionine-foods.php
High methionine foods include
nuts,
beef,
lamb,
cheese,
turkey,
pork,
fish,
shellfish,
soy,
eggs,
dairy, and
beans.
https://www.myfooddata.com/articles/high-methionine-foods.php#methionine-rich-foods
Hcy tiolaktoni ja kardiovaskulaarinen tauti
https://www.ncbi.nlm.nih.gov/pubmed/19261978
Accumulating evidence suggests that homocysteine (Hcy) metabolite, the thioester Hcy-thiolactone, plays an important role in atherothrombosis. Hcy-thiolactone is a product of an error-editing reaction in protein biosynthesis which forms when Hcy is mistakenly selected by methionyl-tRNA synthetase.
The thioester chemistry of Hcy-thiolactone underlies its ability to from isopeptide bonds with protein lysine residues, which impairs or alters protein's function. Protein targets for the modification by Hcy-thiolactone include fibrinogen, low-density lipoprotein, high-density lipoprotein, albumin, hemoglobin, and ferritin.
Pathophysiological consequences of protein N-homocysteinylation include protein and cell damage, activation of an adaptive immune response and synthesis of auto-antibodies against N-Hcy-proteins, and enhanced thrombosis caused by N-Hcy-fibrinogen. Recent development of highly sensitive chemical and immunohistochemical assays has allowed verification of the hypothesis that the Hcy-thiolactone pathway contributes to pathophysiology of the vascular system, in particular of the prediction that conditions predisposing to atherosclerosis, such as genetic or dietary hyperhomocysteinemia, lead to elevation of Hcy-thiolactone and N-Hcy-protein. This prediction has been confirmed in vivo both in humans and in mice. For example, plasma Hcy-thiolactone was found to be elevated 59-72-fold in human patients with hyperhomocysteinemia ( HHcy) secondary to mutations in methylenetetrahydrofolate reductase (MTHFR) or cystathionine beta-synthase (CBS) genes.
Plasma N-Hcy-protein levels are elevated 24-30-fold in MTHFR- or CBS-deficiency, both in human patients and in mice.
Plasma and urinary Hcy-thiolactone and plasma N-Hcy-protein levels are also elevated up to 30-fold in mice fed a hyperhomocysteinemic (1.5% methionine) diet.
Furthermore, plasma levels of prothromobogenic N-Hcy-fibrinogen were elevated in human CBS deficiency, which explains increased atherothrombosis observed in CBS-deficient patients. We also observed increased immunohistochemical staining for N-Hcy-protein in aortic lesions from ApoE-deficient mice with hyperhomocysteinemia induced by a high methionine diet, relative to the mice fed a normal chow diet. We conclude that genetic or dietary hyperhomocysteinemia significantly elevates proatherothrombotic metabolites Hcy-thiolactone and N-Hcy-proteins in humans and mice.
J Physiol Pharmacol. 2008 Dec;59 Suppl 9:155-67.
The pathophysiological hypothesis of homocysteine thiolactone-mediated vascular disease.Abstract
Accumulating evidence suggests that homocysteine (Hcy) metabolite, the thioester Hcy-thiolactone, plays an important role in atherothrombosis. Hcy-thiolactone is a product of an error-editing reaction in protein biosynthesis which forms when Hcy is mistakenly selected by methionyl-tRNA synthetase.
The thioester chemistry of Hcy-thiolactone underlies its ability to from isopeptide bonds with protein lysine residues, which impairs or alters protein's function. Protein targets for the modification by Hcy-thiolactone include fibrinogen, low-density lipoprotein, high-density lipoprotein, albumin, hemoglobin, and ferritin.
Pathophysiological consequences of protein N-homocysteinylation include protein and cell damage, activation of an adaptive immune response and synthesis of auto-antibodies against N-Hcy-proteins, and enhanced thrombosis caused by N-Hcy-fibrinogen. Recent development of highly sensitive chemical and immunohistochemical assays has allowed verification of the hypothesis that the Hcy-thiolactone pathway contributes to pathophysiology of the vascular system, in particular of the prediction that conditions predisposing to atherosclerosis, such as genetic or dietary hyperhomocysteinemia, lead to elevation of Hcy-thiolactone and N-Hcy-protein. This prediction has been confirmed in vivo both in humans and in mice. For example, plasma Hcy-thiolactone was found to be elevated 59-72-fold in human patients with hyperhomocysteinemia ( HHcy) secondary to mutations in methylenetetrahydrofolate reductase (MTHFR) or cystathionine beta-synthase (CBS) genes.
Plasma N-Hcy-protein levels are elevated 24-30-fold in MTHFR- or CBS-deficiency, both in human patients and in mice.
Plasma and urinary Hcy-thiolactone and plasma N-Hcy-protein levels are also elevated up to 30-fold in mice fed a hyperhomocysteinemic (1.5% methionine) diet.
Furthermore, plasma levels of prothromobogenic N-Hcy-fibrinogen were elevated in human CBS deficiency, which explains increased atherothrombosis observed in CBS-deficient patients. We also observed increased immunohistochemical staining for N-Hcy-protein in aortic lesions from ApoE-deficient mice with hyperhomocysteinemia induced by a high methionine diet, relative to the mice fed a normal chow diet. We conclude that genetic or dietary hyperhomocysteinemia significantly elevates proatherothrombotic metabolites Hcy-thiolactone and N-Hcy-proteins in humans and mice.
- PMID:
- 19261978
Tauriinin synteesin tärkeä entsyymi CSAD,cysteinisulfiinihappodekarboksylaasi on B6-vitamiinsita riippuvainen
cysteinesulfinic acid decarboxylase
https://www.ncbi.nlm.nih.gov/pubmed/30131986
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]
https://www.ncbi.nlm.nih.gov/pubmed/30131986
Food Funct. 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
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),
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
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.
- 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
- Cloning of murine cysteine sulfinic acid decarboxylase and its mRNA expression in murine tissues. Park E, et al. Biochim Biophys Acta, 2002 Apr 12. PMID 11997111
- Mechanism of cysteine-dependent inactivation of aspartate/glutamate/cysteine sulfinic acid α-decarboxylases. Liu P, et al. Amino Acids, 2013 Feb. PMID 22718265
- Mammalian CSAD and GADL1 have distinct biochemical properties and patterns of brain expression. Winge I, et al. Neurochem Int, 2015 Nov. PMID 26327310
- Whole genome RNAi screens reveal a critical role of REV3 in coping with replication stress. Kotov IN, et al. Mol Oncol, 2014 Dec. PMID 25113059, Free PMC Article
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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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