Tauriini ja sulfaattihomeostasis : juni 2019

torsdag 20 juni 2019

Sitaatti: "Kystatiini C on emäksinen pienimolekyylinen (mp 13 000) proteiini, jonka fysiologisena tehtävänä on inhiboida kysteiiniproteaaseja. Kaikki elimistön tumalliset solut tuottavat kystatiini C:tä tasaisella nopeudella, se ei ole akuutin faasin proteiini, eivätkä lihasmassa, sukupuoli ja ravinto vaikuta sen seerumi/plasmapitoisuuteen. Kystatiini C eliminoituu lähes täysin glomerulussuodokseen, josta proksimaalisen tubuluksen solut sen reabsorboivat ja hajottavat. Kystatiini C:n ominaisuudet tekevät siitä kreatiniinia paremman glomerulusfunktion merkkiaineen".

Kystatiini C- geeni (PubMed haku 20.6. 2019)

https://www.ncbi.nlm.nih.gov/gene/1471

Official Symbol: CST3
Official Full Name: cystatin C
Also known as: ARMD11; HEL-S-2
Summary: The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including

the type 1 cystatins (stefins),
type 2 cystatins
the kininogens.

The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes the most abundant extracellular inhibitor of cysteine proteases, which is found in high concentrations in biological fluids and is expressed in virtually all organs of the body. A mutation in this gene has been associated with amyloid angiopathy.; Expression of this protein in vascular wall smooth muscle cells is severely reduced in both atherosclerotic and aneurysmal aortic lesions, establishing its role in vascular disease. In addition, this protein has been shown to have an antimicrobial function, inhibiting the replication of herpes simplex virus. Alternative splicing results in multiple transcript variants encoding a single protein. [provided by RefSeq, Nov 2014]
Expression: Ubiquitous expression in brain (RPKM 148.6), salivary gland (RPKM 118.0) and 25 other tissues See more
Orthologs mouse all

Preferred Names: cystatin-C

Names: bA218C14.4 (cystatin C); cystatin 3; epididymis secretory protein Li 2 (HEL-S-2); gamma-trace; neuroendocrine basic polypeptide; post-gamma-globulin

Conserved Domains (1) summary

smart00043 Location:34 → 144: CY; Cystatin-like domain. Cystatins are a family of cysteine protease inhibitors that occur mainly as single domain proteins. However some extracellular proteins such as kininogen, His-rich glycoprotein and fetuin also contain these domains.

FEATURES             Location/Qualifiers
     source          1..146
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="20"
                     /map="20p11.21"
     Protein         1..146
                     /product="cystatin-C precursor"
                     /note="cystatin 3; gamma-trace; post-gamma-globulin;
                     neuroendocrine basic polypeptide; bA218C14.4 (cystatin C);
                     epididymis secretory protein Li 2"
                     /calculated_mol_wt=13347
     sig_peptide     1..26
                     /calculated_mol_wt=2470
     mat_peptide     27..146
                     /product="cystatin-C"
                     /experiment="DESCRIPTION:antimicrobial
                     peptide[PMID:2153254]"
                     /calculated_mol_wt=13347
     Region          34..144
                     /region_name="CY"
                     /note="Cystatin-like domain; smart00043"
                     /db_xref="CDD:214484"
     Site            order(37,81..83,85)
                     /site_type="other"
                     /note="putative proteinase inhibition site"
                     /db_xref="CDD:238002"
     CDS             1..146
                     /gene="CST3"
                     /gene_synonym="ARMD11; HEL-S-2"
                     /coded_by="NM_000099.4:94..534"
                     /db_xref="CCDS:CCDS13158.1"
                     /db_xref="GeneID:1471"
                     /db_xref="HGNC:HGNC:2475"
                     /db_xref="MIM:604312"
ORIGIN      
        1 magplrapll llailavala vspaagsspg kpprlvggpm dasveeegvr raldfavgey
       61 nkasndmyhs ralqvvrark qivagvnyfl dvelgrttct ktqpnldncp fhdqphlkrk
      121 afcsfqiyav pwqgtmtlsk stcqda
//

Related articles in PubMed

Correlations of serum cystatin C level and gene polymorphism with vascular cognitive impairment after acute cerebral infarction. Zeng Q, et al. Neurol Sci, 2019 May. PMID 30805744
Baseline Serum Cystatin C Is a Potential Predictor for Acute Kidney Injury in Patients with Acute Pancreatitis. Chai X, et al. Dis Markers, 2018. PMID 30581500, Free PMC Article
Serum Cystatin C Levels in Twin Pregnancy versus Singleton Pregnancy. Peng J, et al. Lab Med, 2019 Apr 8. PMID 30517681
Cystatin C as an index of acute cerebral infraction recurrence: one-year follow-up study. Dong X, et al. Int J Neurosci, 2019 Jan. PMID 30033802
Association of maternal uric acid and cystatin C serum concentrations with maternal and neonatal cardiovascular risk markers and neonatal body composition: The Ulm SPATZ Health Study. Rothenbacher D, et al. PLoS One, 2018. PMID 30024915, Free PMC Article

See all (507) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Submit: New GeneRIF Correction See all GeneRIFs (436)

Metalloproteinaasien ADAM10/ADAM17 degradomi hajoittaa C-cystiinin:

2019 Jun 17. doi: 10.1007/s00018-019-03184-4. [Epub ahead of print]

Degradome of soluble ADAM10 and ADAM17 metalloproteases.

Scharfenberg F¹, Helbig A²et al. Abstract

Disintegrin and metalloproteinases (ADAMs) 10 and 17 can release the extracellular part of a variety of membrane-bound proteins via ectodomain shedding important for many biological functions. So far, substrate identification focused exclusively on membrane-anchored ADAM10 and ADAM17. However, besides known shedding of ADAM10, we identified ADAM8 as a protease capable of releasing the ADAM17 ectodomain. Therefore, we investigated whether the soluble ectodomains of ADAM10/17 (sADAM10/17) exhibit an altered substrate spectrum compared to their membrane-bound counterparts. A mass spectrometry-based N-terminomics approach identified 134 protein cleavage events in total and 45 common substrates for sADAM10/17 within the secretome of murine cardiomyocytes. Analysis of these cleavage sites confirmed previously identified amino acid preferences. Further in vitro studies verified fibronectin, cystatin C, sN-cadherin, PCPE-1 as well as sAPP as direct substrates of sADAM10 and/or sADAM17. Overall, we present the first degradome study for sADAM10/17, thereby introducing a new mode of proteolytic activity within the protease web. KEYWORDS:

ADAM10; ADAM17; ADAM8; Ectodomain shedding; Proteolysis; TAILS

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

Hcy tiolaktoni ja kardiovaskulaarinen tauti

https://www.ncbi.nlm.nih.gov/pubmed/19261978

2008 Dec;59 Suppl 9:155-67.

The pathophysiological hypothesis of homocysteine thiolactone-mediated vascular disease.

Jakubowski H¹.

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

[Indexed for MEDLINE]

https://www.researchgate.net/publication/309344580/figure/fig2/AS:560734946185217@1510701037501/The-structure-of-methionine-homocysteine-homocysteine-thiolactone-homocysteine-TL.png

https://www.researchgate.net/publication/309344580/figure/fig2/AS:560734946185217@1510701037501/The-structure-of-methionine-homocysteine-homocysteine-thiolactone-homocysteine-TL.png

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.

Zhao F ¹, Gao L , Qin X , Du G , Zhou Y .

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]

CSAD (12q13.3), PCAP
https://www.ncbi.nlm.nih.gov/gene/51380#gene-expression

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:89 → 489: 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

Kissaeläimiltä puuttuu tauriinin synteesikoneista ja siksi ne syövät tauriininsa animaalilähteistä

Kissat syövät hiiriä ehkä tauriinin puutteen takia.

Leijonat, tiikerit ja muut kissaeläimet Felines, ovat ihmiselle nälkäisinä aina vaarallisa, koska ihminen on niille essentiellin tauriinin lähde. Niitten entsyymi cysteiinisulfiinihappodekarboksylaasi on vajeinen ja se on tauriinin synteesiä (rikkipitoisista aminohapoista metioniinista ja cysteiinistä käsin ) rajoittava entsyymi. Metioniinin + cysteiinin saanti taas on ihmisellekin essentielliä - niitä tulee ravinnossa saada tietty määränsä, koska keho ei pysty valmistamaan niitä, korkeintaan muokkaamaan valmiina saatuja kehon interkonversioissa.

Metabolic bone disease in lion cubs at the London Zoo in 1889 - NCBI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994403/

Översätt den här sidan

av RW Chesney - ‎2010 - ‎Citerat av 14 - ‎Relaterade artiklar

24 aug. 2010 - Felines have limited amounts of cysteinesulfinic acid decarboxylase, a rate-limiting enzyme in the synthesis of taurine from methionine and cysteine, hence taurine is an essential amino acid in cats. ... Also, taurine is the most abundant free amino acid in goat milk [36].

Eri tautitiloissa ihmisellä tauriinin synteesi on kompromittoitunutta ja liittyy moniin tauteihin.
Tässä onkin ajateltu jo kehittää tauriinianalogeja, jolloin ylitetään metaboliset esteet ja annetaan suoraan tauriinia tai sen analogia lääkkeenomaisesti- kts. edellinen artikkeli ja sitaattilähde.

Tauriinin ja beta-alaniinin kuljettaja SLC6A (3p25.1) , TAUT

https://www.ncbi.nlm.nih.gov/gene/6533
SLC6A (3p25.1)

Official Symbol: SLC6A6provided by HGNC
Official Full Name: solute carrier family 6 member 6provided by HGNC
Also known as: TAUT
Summary: This gene encodes a multi-pass membrane protein that is a member of a family of sodium and chloride-ion dependent transporters. The encoded protein transports taurine and beta-alanine. There is a pseudogene for this gene on chromosome 21. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
Expression Ubiquitous expression in ovary (RPKM 26.5), spleen (RPKM 20.3) and 23 other tissues See more

Preferred Names: sodium- and chloride-dependent taurine transporter

Names: solute carrier family 6 (neurotransmitter transporter, taurine), member 6

Conserved Domains (1) summary

cd11510 Location:142 → 683: SLC6sbd_TauT; Na(+)- and Cl(-)-dependent taurine transporter; solute-binding domain TauT is a Na(+)- and Cl(-)-dependent, high-affinity, low-capacity transporter of taurine and beta-alanine. Human TauT is encoded by the SLC6A6 gene. TauT is expressed in brain, retina, liver, kidney, heart, spleen, and pancreas. It may play a part in the supply of taurine to the intestinal epithelium and in the between-meal-capture of taurine. It may also participate in re-absorbing taurine that has been deconjugated from bile acids in the distal lumen. Functional TauT protects kidney cells from nephrotoxicity caused by the chemotherapeutic agent cisplatin; cisplatin down-regulates TauT in a p53-dependent manner. In mice, TauT has been shown to be important for the maintenance of skeletal muscle function and total exercise capacity. TauT-/- mice develop additional clinically important diseases, some of which are characterized by apoptosis, including vision loss, olfactory dysfunction, and chronic liver disease. This subgroup belongs to the solute carrier 6 (SLC6) transporter family.

ORIGIN      
        1 mgdaescllr qqtrevrkkp linyrflraa anaeprgpqa qrtscakrec gaftqrvrer
       61 agrqppaggt rhsraergrr rshprsrtrt tallrssqtk ematkeklqc lkdfhkdilk
      121 pspgkspgtr pedeaegkpp qrekwsskid fvlsvaggfv glgnvwrfpy lcykngggaf
      181 lipyfiflfg sglpvfflei iigqytsegg itcwekicpl fsgigyasvv ivsllnvyyi
      241 vilawatyyl fqsfqkelpw ahcnhswntp hcmedtmrkn ksvwitisst nftspviefw
      301 ernvlslspg idhpgslkwd lalclllvwl vcffciwkgv rstgkvvyft atfpfamllv
      361 llvrgltlpg agagikfyly pditrledpq vwidagtqif fsyaiclgam tslgsynkyk
      421 ynsyrdcmll gclnsgtsfv sgfaifsilg fmaqeqgvdi advaesgpgl afiaypkavt
      481 mmplptfwsi lffimllllg ldsqfveveg qitslvdlyp sflrkgyrre ifiafvcsis
      541 yllgltmvte ggmyvfqlfd yyaasgvcll wvaffecfvi awiyggdnly dgiedmigyr
      601 pgpwmkyswa vitpvlcvgc fifslvkyvp ltynktyvyp nwaiglgwsl alssmlcvpl
      661 vivirlcqte gpflvrvkyl ltprepnrwa veregatpyn srtvmngalv kpthiivetm
      721 m
//

Tauriini ja sulfaattihomeostasis

torsdag 20 juni 2019

Cystatiini C hyödynnetään munuaistutkimuksissa , CST3( 20p11.21), ARMD11, HEL-S-2.

Yleistä http://oyslab.fi/ohjekirja/1887.html

Kystatiini C- geeni (PubMed haku 20.6. 2019)

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

onsdag 19 juni 2019

Haku " rhodanese" Thiosulphate sulfurtransferase. Paljon uutisia. 2019

Rodaneesi entsyymi on tiosulfaattisulfotransferaasi

L-cysteiiniä proteiinisynteesiin eikä D-cysteiiniä

Abstract

H2S merkityksestä mm. sirtuiinien signalointitiessä

Role of Hydrogen Sulfide in NRF2- and Sirtuin-Dependent Maintenance of Cellular Redox Balance. Corsello T¹, Komaravelli N², Casola A^3,⁴.

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.

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)

tisdag 18 juni 2019

Hyvin metioniinipitoinen dieetti

Hcy tiolaktoni ja kardiovaskulaarinen tauti

Abstract

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

Abstract

Kissaeläimiltä puuttuu tauriinin synteesikoneista ja siksi ne syövät tauriininsa animaalilähteistä

Metabolic bone disease in lion cubs at the London Zoo in 1889 - NCBI

Tauriinin ja beta-alaniinin kuljettaja SLC6A (3p25.1) , TAUT

Leta i den här bloggen

Mikä tauriini on

torsdag 20 juni 2019

Yleistä http://oyslab.fi/ohjekirja/1887.html

Kystatiini C- geeni (PubMed haku 20.6. 2019)

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

onsdag 19 juni 2019

Abstract

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.

KEYWORDS: NRF2; hydrogen sulfide; oxidative stress; redox; sirtuin

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)

tisdag 18 juni 2019

Abstract

Abstract

Role of Hydrogen Sulfide in NRF2- and Sirtuin-Dependent Maintenance of Cellular Redox Balance. Corsello T¹, Komaravelli N², Casola A^3,⁴.