ihmisen sytosolisesta AcetylCoa syntetaasista ACSS2 (20q11.22)

 (Mainitsen että aiemmin sain eräästä lähteestä tietää, että vain sirtuiini SIRT1 pystyy deasetyloimaan tätä sytosolista asetyyliCoA-syntaasia, kun taas mitokondriaalista deasetyloi SIRT3. )


 ACSS2 ( 20q11.22), sytosolinen asetyyliCoA syntetaasi, etikkahapon aktivoija.
https://www.ncbi.nlm.nih.gov/gene/55902
Tämä geeni koodaa sytosolista etnsyymiä, joka  katalysoi etikkahapon aktivoitumista   ja  tämä aktivoitunut etikkahappo  voi käyttyä lipidisynteesiin tai energian generoimiseen. Proteiini toimii monomeerina ja  tuottaa asetyyli-CoA:n etikkahaposta reaktiossa, joka vaatii ATP:tä.
 Tämän geenin ilmentymää säätelee SREB- proteiinit, transkriptiotekijät, jotka aktivoivat geenejä, mitä vaaditaan  kolesterolin ja tyydyttymättömien rasvahappojen synteesin. Vaihtoehtoispleissauksista tulee useita  transkriptivariantteja. Geeniä ilmentyy laajasti rasvakudoksessa, pohjukaissuolesas ja 24 muussa kudoksessa. 

Official Symbol ACSS2

Official Full Name acyl-CoA synthetase short chain family member 2

Also known as ACS; ACSA; ACAS2; ACECS; dJ1161H23.1

Summary: This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP.

 Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

Expression: Broad expression in fat (RPKM 49.2), duodenum (RPKM 47.1) and 24 other tissues See more. Orthologs. mouse all.

Preferred Names

acetyl-coenzyme A synthetase, cytoplasmic

Names

acetate thiokinase

acetate-CoA ligase

acetyl-Coenzyme A synthetase 2 (ADP forming)

acyl-activating enzyme

cytoplasmic acetyl-coenzyme A synthetase

 

( Millä tavalla sytosolinen ja mitokondriaalinen ACSS eroavat  toisistaan rakenteellisesti? Mm. vaikuttaa olevan kuusi seriinifosforylaatiota ja vain yksi N-lysiiniasetylaatio tässä sytosolisessa. Tämä geeni sijaitsee saman kromosomin q päädyssä, kun mitokondrinen  ACSS taas sijaitsee p-päädyssä).

  

Features. 

NM_001076552.2 → NP_001070020.2  acetyl-coenzyme A synthetase, cytoplasmic isoform 2

 

FEATURES             Location/Qualifiers
     source          1..714
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="20"
                     /map="20q11.22"
     Protein         1..714
                     /product="acetyl-coenzyme A synthetase, cytoplasmic
                     isoform 2"
                     /EC_number="6.2.1.1"
                     /note="acetyl-Coenzyme A synthetase 2 (ADP forming);
                     cytoplasmic acetyl-coenzyme A synthetase; acetate-CoA
                     ligase; acyl-activating enzyme; acetate thiokinase;
                     acetyl-coenzyme A synthetase, cytoplasmic"
                     /calculated_mol_wt=79957
     Site            28
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:23186163,
                     ECO:0000244|PubMed:24275569}; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            30
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:18669648,
                     ECO:0000244|PubMed:23186163, ECO:0000244|PubMed:24275569};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Region          31..705
                     /region_name="PRK00174"
                     /note="acetyl-CoA synthetase; Provisional"
                     /db_xref="CDD:234677"
     Site            36
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:24275569};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Region          51..698
                     /region_name="ACS"
                     /note="Acetyl-CoA synthetase (also known as acetate-CoA
                     ligase and acetyl-activating enzyme); cd05966"
                     /db_xref="CDD:213313"
     Site            order(191..193,219,222,224,370,375..376,398..400,424..425,
                     428,451..454,476..481,565,577,580,588..591,649,654..655)
                     /site_type="active"
                     /db_xref="CDD:213313"
     Site            order(191..193,219,222,224,370,376,398..400,424..425,428,
                     588..590,649,654)
                     /site_type="other"
                     /note="CoA binding site [chemical binding]"
                     /db_xref="CDD:213313"
     Region          219..222
                     /region_name="Coenzyme A binding. {ECO:0000250}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            263
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000250|UniProtKB:Q9QXG4};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            265
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000250|UniProtKB:Q9QXG4};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            267
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:18669648,
                     ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:23186163,
                     ECO:0000244|PubMed:24275569}; propagated from
                     UniProtKB/Swiss-Prot (Q9NR19.1)"
     Site            order(326,329..334,336..337)
                     /site_type="other"
                     /note="acyl-activating enzyme (AAE) consensus motif"
                     /db_xref="CDD:213313"
     Site            order(375..376,451..454,476..481,565,577,580,591)
                     /site_type="other"
                     /note="AMP binding site [chemical binding]"
                     /db_xref="CDD:213313"
     Site            order(375..376,451..452,479)
                     /site_type="other"
                     /note="acetate binding site [chemical binding]"
                     /db_xref="CDD:213313"
     Site            431
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine. {ECO:0000244|PubMed:19608861};
                     propagated from UniProtKB/Swiss-Prot (Q9NR19.1)"
     CDS             1..714
                     /gene="ACSS2"
                     /gene_synonym="ACAS2; ACECS; ACS; ACSA; dJ1161H23.1"
                     /coded_by="NM_001076552.2:122..2266"
                     /note="isoform 2 is encoded by transcript variant 2"
                     /db_xref="CCDS:CCDS42868.2"
                     /db_xref="GeneID:55902"
                     /db_xref="HGNC:HGNC:15814"
                     /db_xref="MIM:605832"
ORIGIN      
        1 mglpeervrs gsgsrgqeea gaggrarsws pppevsrsah vpslqryrel hrrsveepre
       61 fwgdiakefy wktpcpgpfl rynfdvtkgk ifiewmkgat tnicynvldr nvhekklgdk
      121 vafywegnep gettqityhq llvqvcqfsn vlrkqgiqkg drvaiympmi pelvvamlac
      181 arigalhsiv fagfsseslc erildsscsl littdafyrg eklvnlkela dealqkcqek
      241 gfpvrccivv khlgraelgm gdstsqsppi krscpdvqgk lkekskrvqp qiswnqgidl
      301 wwhelmqeag decepewcda edplfilyts gstgkpkgvv htvggymlyv attfkyvfdf
      361 haedvfwcta digwitghsy vtygplanga tsvlfegipt ypdvnrlwsi vdkykvtkfy
      421 taptairllm Kfgdepvtkh sraslqvlgt vgepinpeaw lwyhrvvgaq rcpivdtfwq
      481 tetgghmltp lpgatpmkpg satfpffgva pailnesgee legeaegylv fkqpwpgimr
      541 tvygnherfe ttyfkkfpgy yvtgdgcqrd qdgyywitgr iddmlnvsgh llstaevesa
      601 lveheavaea avvghphpvk geclycfvtl cdghtfspkl teelkkqire kigpiatpdy
      661 iqnapglpkt rsgkimrrvl rkiaqndhdl gdmstvadps vishlfshrc ltiq
//

(Mitä tietoja on tästä proteiinista saatu tähän mennessä?)

 

Related articles in PubMed

1. Acetyl-CoA synthetase 2 enhances tumorigenesis and is indicative of a poor prognosis for patients with renal cell carcinoma. Zhang S, et al. Urol Oncol, 2018 May. PMID 29503142
2. Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression. Yao L, et al. Cell Physiol Biochem, 2018. PMID 29444517
3. Local histone acetylation by ACSS2 promotes gene transcription for lysosomal biogenesis and autophagy. Li X, et al. Autophagy, 2017 Oct 3. PMID 28820290, Free PMC Article
4. Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy. Li X, et al. Mol Cell, 2017 Jun 1. PMID 28552616, Free PMC Article
5. Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation. Bulusu V, et al. Cell Rep, 2017 Jan 17. PMID 28099844, Free PMC Article

See all (32) citations in PubMed

GeneRIFs: Gene References Into Functions

1. High ACSS2 expression is associated with renal cell carcinoma.
2. A novel biologic role for ACSS2 in recycling of nuclear acetate for histone acetylation to promote lysosomal and autophagy-related gene expression and counteract nutritional stress, highlighting the importance of ACSS2 in maintaining autophagy and lysosome-mediated cellular energy homeostasis during tumor development.
3. ACLY and ACSS2 are both activated to produce cytosolic Ac-CoA from glucose carbon for lipogenesis during human cytomegalovirus infection.
4. ACSS2 is an important factor for promoting RCC development and is essential for cell migration and invasion, which it promotes by increasing the expression of LAMP1.
5. these findings suggest that downregulation of acetyl-CoA synthetase-2 expression is a metabolic hallmark of tumor progression and aggressive behavior in colorectal carcinoma.
6. Exogenous acetate augments Acss2/HIF-2 dependent cancer growth and metastasis in cell culture and mouse models
7. The nuclear-cytosolic acetyl-CoA synthetase 2 recaptures acetate released from histone deacetylation for recycling by histone acetyltransferases.
8. In a Honduran population, the odds of having nonsyndromic cleft lip/palate (NSCLP) among carriers of the ACSS2 variant was 4.0 with a carrier frequency of 7.1% in unrelated affected and 1.9% in unrelated unaffected individuals. In a Colombian population, the odds of having NSCLP among carriers of the ACSS2 variant was 2.6 with a carrier frequency of 10.0% in unrelated affected and 4.1% in unrelated unaffected individuals.
9. In the nucleus, ACSS2 binds to transcription factor EB and translocates to lysosomal and autophagy gene promoter regions, where ACSS2 incorporates acetate generated from histone acetylation turnover to locally produce acetyl-CoA for histone H3 acetylation in these regions and promote lysosomal biogenesis, autophagy, cell survival, and brain tumorigenesis.
10. ACSS2 is essential for glucose-independent acetate-mediated cell survival and tumor growth.

Submit: New GeneRIF Correction See all GeneRIFs (21)

https://www.ncbi.nlm.nih.gov/pubmed/?term=ACSS2%2C+Sirtuins 
https://www.ncbi.nlm.nih.gov/pubmed/?term=ACSS2%2C++hypercholesterolemia 
(Joku toinenkin on kiinnittänyt huomion ACSS- geenien  sijaintiin ja ominaisuuksiin ja  ei koodaavan pitkän RNA:n mahdolliseen  osuuteen. Otan aivan  tuoreen artikkelin pohdittavaksi. ACSS1 ja ACSS2  pitävät lyhyistä ja keskipitkistä rasvahapoista C2-C5  ensisijaisena kohteena C2 etikkahappoa.)  
https://www.ncbi.nlm.nih.gov/pubmed/31281828 

Int J Genomics. 2019 Jun 2;2019:5070975. doi: 10.1155/2019/5070975. eCollection 2019.

Identification of lncRNAs and Genes Responsible for Fatness and Fatty Acid Composition Traits between the Tibetan and Yorkshire Pigs.

Shang P¹, Li W², Liu G³, Zhang J¹, Li M¹, Wu L¹, Wang K², Chamba Y¹.

Abstract

Tibetan pigs from the Tibetan Plateau are characterized with a significant phenotypic difference relative to lowland pigs. In this study, a significant difference of the fatness and fatty acid composition traits was observed between the Tibetan and Yorkshire pigs. To uncover the involved mechanism, the expression profile of long noncoding RNAs (lncRNAs) and genes was compared between them. After serial filtered steps, 1,964 lncRNAs were obtained through our computational pipeline. In total, 63 and 715 lncRNAs and genes were identified to be differentially expressed. Evidence from cis- and trans-targeting analysis of lncRNAs demonstrated that some lncRNAs, such as MSTRG.14097 and MSTRG.8034, played important roles in the fatness and fatty acid composition traits. Bioinformatics analysis revealed that many candidate genes were responsible for the two traits. Of these, FASN, ACACA, SCD, ME3, PDHB, ACSS1, ACSS2, and ACLY were identified, which functioned in regulating the level of hexadecanoic acid, hexadecenoic acid, octadecenoic acid, and monounsaturated fatty acid. And LPGAT1, PDK4, ACAA1, and ADIPOQ were associated with the content of stearic acid, octadecadienoic acid, and polyunsaturated fatty acid. Candidate genes, which were responsible for fatness trait, consisted of FGF2, PLAG1, ADIPOQ, IRX3, MIF, IL-34, ADAM8, HMOX1, Vav1, and TLR8. In addition, association analysis also revealed that 34 and 57 genes significantly correlated to the fatness and fatty acid composition trait, respectively. Working out the mechanism caused by these lncRNAs and candidate genes is proven to be complicated but is invaluable to our understanding of fatness and fatty acid composition traits.

Aktivoidusta etikkahaposta ihmisen solussa ja mitokondriassa. Mitokondriaalinen ACSS1( 20p11.21)

AceSC1 ja AceC2
https://www.ncbi.nlm.nih.gov/pubmed/11150295
Näillä on nykyisin toiset  nimetm joissa numero on päinvastoin siis  ACSS2 sytosolinen  (AceCS1 ennen) ja  ACSS1 mitokondriaalinen ( AceCS2 ennen). Mitokondriaalista on eniten sydämessä ja maksasta se puuttuu.

AseCS1 on mitokondriaalinen asetyyli-CoA-syntetaasi. (Asetaatti-CoA ligaasi;  etikkahapon CoA-ligaasi) ,  Sillä on ainakin hiirissä - (joilla ei liikuntafaktoristaole puutetta)    tärkeä osuus sitruunahapposyklissä (CSC, TCA) , jossa se katalysoi asetaatit eli etikkahapon konversiota aktiiviksi etikkahapoksi , asetyyli CoA:ksi.( AsetyyliCoA taas on se perustava molekyyli, jolla on heti käyttöä monenmoisiin  metabolisiin teihin! Pelkkä etikkahappo taas tuottaa  harmia, jos se ei  kykene aktivoitumaan).  Geenistä pleissautuu  vaihtoehtoisia transkriptejä, jotka koodaavat  monia isoformeja. Tätä geeniä ilmentyy istukassa, pohjukaisisuolessa ja 24 muussa kudoksessa.
Geenin virallinen symboli nykyään on ACSS1, muita nimiä ovat ACAS2L, ACECS1, AceCS2L

ACSS1 (20p11.21) . acyl-CoA synthetase short chain family member 1 [ Homo sapiens (human) ]
https://www.ncbi.nlm.nih.gov/gene/84532

Official Symbol ACSS1

Official Full Name acyl-CoA synthetase short chain family member 1

Also known as ACAS2L; ACECS1; AceCS2L

Summary:  This gene encodes a mitochondrial acetyl-CoA synthetase enzyme. A similar protein in mice plays an important role in the tricarboxylic acid cycle by catalyzing the conversion of acetate to acetyl CoA. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

Expression Broad expression in placenta (RPKM 70.4), duodenum (RPKM 23.0) and 24 other tissues See more Orthologs mouse all

Preferred Names: acetyl-coenzyme A synthetase 2-like, mitochondrial

Names: acetate--CoA ligase 2

Features: NM_001252675.1 → NP_001239604.1  acetyl-coenzyme A synthetase 2-like, mitochondrial isoform 2 precursor   ( Plenty of  isoforms!)

 

 

FEATURES             Location/Qualifiers
     source          1..687
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="20"
                     /map="20p11.21"
     Protein         1..687
                     /product="acetyl-coenzyme A synthetase 2-like,
                     mitochondrial isoform 2 precursor"
                     /EC_number="6.2.1.1"
                     /note="acetyl-coenzyme A synthetase 2-like, mitochondrial;
                     acetate--CoA ligase 2"
                     /calculated_mol_wt=70901
     transit_peptide 1..37
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Mitochondrion. {ECO:0000269|PubMed:16788062};
                     propagated from UniProtKB/Swiss-Prot (Q9NUB1.2)"
                     /calculated_mol_wt=3743
     Region          54..674
                     /region_name="Ac_CoA_lig_AcsA"
                     /note="acetate--CoA ligase; TIGR02188"
                     /db_xref="CDD:274022"
     Region          64..665
                     /region_name="ACS"
                     /note="Acetyl-CoA synthetase (also known as acetate-CoA
                     ligase and acetyl-activating enzyme); cd05966"
                     /db_xref="CDD:213313"

Acetyl-CoA synthetase (also known as acetate-CoA ligase and acetyl-activating enzyme)
Acetyl-CoA
 synthetase (ACS) catalyzes the formation of acetyl-CoA from acetate, 
CoA, and ATP. Synthesis of acetyl-CoA is carried out in a two-step 
reaction. In the first step, the enzyme catalyzes the synthesis of 
acetyl-AMP intermediate from acetate and ATP. In the second step, 
acetyl-AMP reacts with CoA to produce acetyl-CoA. This enzyme is widely 
present in all living organisms. The activity of this enzyme is crucial 
for maintaining the required levels of acetyl-CoA, a key intermediate in
 many important biosynthetic and catabolic processes. Acetyl-CoA is used
 in the biosynthesis of glucose, fatty acids, and cholesterol. It can 
also be used in the production of energy in the citric acid cycle. 
Eukaryotes typically have two isoforms of acetyl-CoA synthetase, a 
cytosolic form involved in biosynthetic processes and a mitochondrial 
form primarily involved in energy generation.
     Site            order(196..198,224,227,229,335,340..341,363..365,389..390,
                     393,416..419,441..446,531,543,546,554..557,615,620..621)
                     /site_type="active"
                     /db_xref="CDD:213313"
     Site            order(196..198,224,227,229,335,341,363..365,389..390,393,
                     554..556,615,620)
                     /site_type="other"
                     /note="CoA binding site [chemical binding]"
                     /db_xref="CDD:213313"
     Region          224..227  (RGGR)
                     /region_name="Coenzyme A binding. {ECO:0000250}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9NUB1.2)"
     Site            order(291,294..299,301..302)
                     /site_type="other"
                     /note="acyl-activating enzyme (AAE) consensus motif"
                     /db_xref="CDD:213313"
     Site            order(340..341,416..419,441..446,531,543,546,557)
                     /site_type="other"
                     /note="AMP binding site [chemical binding]"
                     /db_xref="CDD:213313"
     Site            order(340..341,416..417,444)
                     /site_type="other"
                     /note="acetate binding site [chemical binding]"
                     /db_xref="CDD:213313"
     Site            396 K
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine. {ECO:0000244|PubMed:19608861};
                     propagated from UniProtKB/Swiss-Prot (Q9NUB1.2)"
     Site            640 K
                     /site_type="acetylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="N6-acetyllysine. {ECO:0000269|PubMed:16788062};
                     propagated from UniProtKB/Swiss-Prot (Q9NUB1.2)"
     CDS             1..687
                     /gene="ACSS1"
                     /gene_synonym="ACAS2L; ACECS1; AceCS2L"
                     /coded_by="NM_001252675.1:81..2144"
                     /note="isoform 2 precursor is encoded by transcript
                     variant 2"
                     /db_xref="GeneID:84532"
                     /db_xref="HGNC:HGNC:16091"
                     /db_xref="MIM:614355"
ORIGIN      
        1 maartlgrgv grllgslrgl sgqparppcg vsaprraasg psgsapavaa aaaqpgsypa
       61 lsaqaarepa afwgplardt lvwdtpyhtv wdcdfstgki gwflggqlnv svncldqhvr
      121 kspesvaliw erdepgtevr ityrellett crlantlkrh gvhrgdrvai ympvsplava
      181 amlacariga vhtvifagfs aeslagrind akckvvitfn qglrggrvve lkkivdeavk
      241 hcptvqhvlv ahrtdnkvhm gdldvpleqe makedpvcap esmgsedmlf mlytsgstgm
      301 pkgivhtqag yllyaalthk lvfdhqpgdi fgcvadigwi tghsyvvygp lcngatsvlf
      361 estpvypnag rywetverlk inqfygapta vrlllKygda wvkkydrssl rtlgsvgepi
      421 nceawewlhr vvgdsrctlv dtwwqtggic iaprpseega eilpamamrp ffgivpvlmd
      481 ekgsvvegsn vsgalcisqa wpgmartiyg dhqrfvdayf kaypgyyftg dgayrteggy
      541 yqitgrmddv inisghrlgt aeiedaiadh pavpesavig yphdikgeaa fafivvkdsa
      601 gdsdvvvqel ksmvatkiak yavpdeilvv krlpktrsgK vmrrllrkii tseaqelgdt
      661 ttledpsiia eilsvyqkck dkqaaak
//

 

 

 

 

Mitä  tutkimuksia tästä geenituotteesta on saatavilla?  Huomaa SIRT3:n osuus mitokondriassa!

Related articles in PubMed

1. Gene network analysis reveals a novel 22-gene signature of carbon metabolism in hepatocellular carcinoma. Zhang J, et al. Oncotarget, 2016 Aug 2. PMID 27363021, Free PMC Article
2. A novel Acetyl-CoA synthetase short-chain subfamily member 1 (Acss1) gene indicates a dynamic history of paralogue retention and loss in vertebrates. Castro LF, et al. Gene, 2012 Apr 15. PMID 22313524
3. The importance of acetyl coenzyme A synthetase for 11C-acetate uptake and cell survival in hepatocellular carcinoma. Yun M, et al. J Nucl Med, 2009 Aug. PMID 19617323
4. Crystal structures of human SIRT3 displaying substrate-induced conformational changes. Jin L, et al. J Biol Chem, 2009 Sep 4. PMID 19535340, Free PMC ArticleAbstract
   SIRT3 is a major mitochondrial NAD(+)-dependent protein deacetylase playing important roles in regulating mitochondrial metabolism and energy production and has been linked to the beneficial effects of exercise and caloric restriction. SIRT3 is emerging as a potential therapeutic target to treat metabolic and neurological diseases. We report the first sets of crystal structures of human SIRT3, an apo-structure with no substrate, a structure with a peptide containing acetyl lysine of its natural substrate acetyl-CoA synthetase 2 (ACSS1) , a reaction intermediate structure trapped by a thioacetyl peptide, and a structure with the dethioacetylated peptide bound. These structures provide insights into the conformational changes induced by the two substrates required for the reaction, the acetylated substrate peptide and NAD(+). In addition, the binding study by isothermal titration calorimetry suggests that the acetylated peptide is the first substrate to bind to SIRT3, before NAD(+). These structures and biophysical studies provide key insight into the structural and functional relationship of the SIRT3 deacetylation activity. DOI:10.1074/jbc.M109.014928[Indexed for MEDLINE]
   Free PMC Article  
   http://www.jbc.org/content/284/36/24394/F5.expansion.html
5. Glucose-independent Acetate Metabolism Promotes Melanoma Cell Survival and Tumor Growth. Lakhter AJ, et al. J Biol Chem, 2016 Oct 14. PMID 27539851, Free PMC ArticleTumors rely on multiple nutrients to meet cellular bioenergetics and macromolecular synthesis demands of rapidly dividing cells. Although the role of glucose and glutamine in cancer metabolism is well understood, the relative contribution of acetate metabolism remains to be clarified. We show that glutamine supplementation is not sufficient to prevent loss of cell viability in a subset of glucose-deprived melanoma cells, but synergizes with acetate to support cell survival. Glucose-deprived melanoma cells depend on both oxidative phosphorylation and acetate metabolism for cell survival. Acetate supplementation significantly contributed to maintenance of ATP levels in glucose-starved cells. Unlike acetate, short chain fatty acids such as butyrate and propionate failed to prevent loss of cell viability from glucose deprivation. In vivo studies revealed that in addition to nucleo-cytoplasmic acetate assimilating enzyme ACSS2, mitochondrial ACSS1 was critical for melanoma tumor growth in mice. Our data indicate that acetate metabolism may be a potential therapeutic target for BRAF mutant melanoma.

See all (24) citations in PubMed

GeneRIFs: Gene References Into Functions

1. citrate synthase and ACSS1 have tumorigenic functions in hepatocellular carcinoma
2. ACSS1 is essential for glucose-independent acetate-mediated cell survival and tumor growth.
3. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
4. Observational study of gene-disease association. (HuGE Navigator)

Kommentti: Kommentti seuraavan otsikon alla siteeraan lähdetietoa systolisesta asetyyliCoA syntetaasista.

 

 

Teknisesti syntetisoidusta aktivoidusta etikkahaposta, AcetylCoA

Ensinnäkin näyttää yritetyn syntetisoida aktivoitunutta etikkahappoa ja tästä on iso juttu netissä. Linkki tähän:
https://www.nature.com/articles/s41467-019-09095-z
Mahtava onnistunut synteesi on tehty aivan äskettäin ja artikkeli on uunituore maaliskuusta 2019:
Muta nyt otin tämän aiheen sen takia, että katson sirtuiinien osuutta  etikkahapon ja aktiivin etikkahapon sykliin. 

• PDF

Article | Open | Published: 26 March 2019

Constructing a synthetic pathway for acetyl-coenzyme A from one-carbon through enzyme design

• Xiaoyun Lu,
• Yuwan Liu,
• […]
• Huifeng Jiang 

Nature Communicationsvolume 10, Article number: 1378 (2019) | Download Citation

isopropyylisitraatti E384

Synonym(s) Isopropyl Citrate mixture Functional Classes Antioxidant Preservative Sequestrant  Click here to search the FAO JECFA database for the specifications of additive(s) with INS No. 384  Click here to search the WHO JECFA database for evaluation of additive(s) with INS No. 384

GSFA Provisions for Isopropyl citrates Number Food Category Max Level Notes 08.3.1.2 Cured (including salted) and dried non-heat treated processed comminuted meat, poultry, and game products 200 mg/kg 08.2.1.2 Cured (including salted) and dried non-heat treated processed meat, poultry, and game products in whole pieces or cuts 200 mg/kg 02.2.2 Fat spreads, dairy fat spreads and blended spreads 100 mg/kg 08.1.2 Fresh meat, poultry, and game, comminuted 200 mg/kg 02.1.3 Lard, tallow, fish oil, and other animal fats 200 mg/kg 02.1.2 Vegetable oils and fats 200 mg/kg 14.1.4 Water-based flavoured drinks, including "sport," "energy," or "electrolyte" drinks and particulated drinks 200 mg/kg Note: Unless otherwise specified, food additive provisions apply to the food category indicated (e.g. Dairy), as well as to all subcategories of that category (e.g. Cheese, Ripened Cheese, etc.).

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Isopropyl citrates (384)

Propionihappo E280

GSFA Online Updated up to the 41th Session of the Codex Alimentarius Commission (2018)

GSFA Provisions for Propionic acid Number Food Category Max Level Notes 01.6.6 Whey protein cheese 3,000 mg/kg Note 70 Note: Unless otherwise specified, food additive provisions apply to the food category indicated (e.g. Dairy), as well as to all subcategories of that category (e.g. Cheese, Ripened Cheese, etc.). GSFA Table 3 Provisions Propionic acid is a food additive that is included in Table 3, and as such may be used in the following foods under the conditions of good manufacturing practices (GMP) as outlined in the Preamble of the Codex GSFA. Although not listed below, Propionic acid could also be used in heat-treated butter milk of food category 01.1.1 and spices of food category 12.2.1. Note that food categories listed in the Annex to Table 3 were excluded accordingly. Propionic acid is acceptable in foods conforming to the following commodity standards: CS 117-1981 CS 291-2010 Number Food Category 01.1.4 Flavoured fluid milk drinks 01.3 Condensed milk and analogues (plain) 01.4.3 Clotted cream (plain) 01.4.4 Cream analogues 01.5 Milk powder and cream powder and powder analogues (plain) 01.6.1 Unripened cheese 01.6.2 Ripened cheese 01.6.4 Processed cheese 01.6.5 Cheese analogues 01.7 Dairy-based desserts (e.g. pudding, fruit or flavoured yoghurt) 01.8.1 Liquid whey and whey products, excluding whey cheeses 02.2.2 Fat spreads, dairy fat spreads and blended spreads 02.3 Fat emulsions mainly of type oil-in-water, including mixed and/or flavoured products based on fat emulsions 02.4 Fat-based desserts excluding dairy-based dessert products of food category 01.7 03.0 Edible ices, including sherbet and sorbet 04.1.2 Processed fruit 04.2.2.2 Dried vegetables (including mushrooms and fungi, roots and tubers, pulses and legumes, and aloe vera), seaweeds, and nuts and seeds 04.2.2.3 Vegetables (including mushrooms and fungi, roots and tubers, pulses and legumes, and aloe vera), and seaweeds in vinegar, oil, brine, or soybean sauce 04.2.2.4 Canned or bottled (pasteurized) or retort pouch vegetables (including mushrooms and fungi, roots and tubers, pulses and legumes, and aloe vera), and seaweeds 04.2.2.5 Vegetable (including mushrooms and fungi, roots and tubers, pulses and legumes, and aloe vera), seaweed, and nut and seed purees and spreads (e.g., peanut butter) 04.2.2.6 Vegetable (including mushrooms and fungi, roots and tubers, pulses and legumes, and aloe vera), seaweed, and nut and seed pulps and preparations (e.g. vegetable desserts and sauces, candied vegetables) other than food category 04.2.2.5 04.2.2.8 Cooked or fried vegetables (including mushrooms and fungi, roots and tubers, pulses and legumes, and aloe vera), and seaweeds 05.0 Confectionery 06.3 Breakfast cereals, including rolled oats 06.4.3 Pre-cooked pastas and noodles and like products 06.5 Cereal and starch based desserts (e.g. rice pudding, tapioca pudding) 06.6 Batters (e.g. for breading or batters for fish or poultry) 06.7 Pre-cooked or processed rice products, including rice cakes (Oriental type only) 06.8 Soybean products (excluding soybean-based seasonings and condiments of food category 12.9) 07.0 Bakery wares 08.2 Processed meat, poultry, and game products in whole pieces or cuts 08.3 Processed comminuted meat, poultry, and game products 08.4 Edible casings (e.g. sausage casings) 09.3 Semi-preserved fish and fish products, including mollusks, crustaceans, and echinoderms 09.4 Fully preserved, including canned or fermented fish and fish products, including mollusks, crustaceans, and echinoderms 10.2.3 Dried and/or heat coagulated egg products 10.3 Preserved eggs, including alkaline, salted, and canned eggs 10.4 Egg-based desserts (e.g. custard) 11.6 Table-top sweeteners, including those containing high-intensity sweeteners 12.2.2 Seasonings and condiments 12.3 Vinegars 12.4 Mustards 12.5 Soups and broths 12.6 Sauces and like products 12.7 Salads (e.g. macaroni salad, potato salad) and sandwich spreads excluding cocoa- and nut-based spreads of food categories 04.2.2.5 and 05.1.3 12.8 Yeast and like products 12.9 Soybean-based seasonings and condiments 12.10 Protein products other than from soybeans 13.3 Dietetic foods intended for special medical purposes (excluding products of food category 13.1) 13.4 Dietetic formulae for slimming purposes and weight reduction 13.5 Dietetic foods (e.g. supplementary foods for dietary use) excluding products of food categories 13.1 - 13.4 and 13.6 13.6 Food supplements 14.1.4 Water-based flavoured drinks, including "sport," "energy," or "electrolyte" drinks and particulated drinks 14.2.1 Beer and malt beverages 14.2.2 Cider and perry 14.2.4 Wines (other than grape) 14.2.5 Mead 14.2.6 Distilled spirituous beverages containing more than 15% alcohol 14.2.7 Aromatized alcoholic beverages (e.g. beer, wine and spirituous cooler-type beverages, low alcoholic refreshers) 15.0 Ready-to-eat savouries 16.0 Prepared foods Note: Unless otherwise specified, food additive provisions apply to the food category indicated (e.g. Dairy), as well as to all subcategories of that category (e.g. Cheese, Ripened Cheese, etc.).

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