tisdag 7 mars 2023

Pitkäketjuisten essentiellien rasvahappojen osuudet nykyajan dieeteissä

https://pubmed.ncbi.nlm.nih.gov/16876396/

Pohdittavaa! Onko nykyajan suositukset evoluutionäkökohdasta käsin aivan parhainta mahdollista tieteellistä tietoa ihmisen perustavista ravitsemuksellisista tarpeista? Yleensä perustetaan suositukset ihmisten käyttämään yleiseen ravintoon nykyaikana eikä ihmisen evolutionaaliseen ravitsemukseen esim satoja vuosia sitten. tosin tietämys on vain possulkevaa tietoa. Silloin EI OLLUT nykyaan prosessoituja ja modifioituja ja jalostettuja ym tuotteita ainakaan, vaikka sodan, kadon, ruton ja genosidisten piirteiden ravinnonsaantiin vaikuttamat asiat lienevät kaikkina aikoina samanlaisen alkeellisia.

doi: 10.1016/j.plefa.2006.05.010. Epub 2006 Jul 28.

Long-chain polyunsaturated fatty acids in maternal and infant nutrition

Frits A J Muskiet¹, Saskia A van Goor, Remko S Kuipers, Francien V Velzing-Aarts, Ella N Smit, Hylco Bouwstra, D A Janneke Dijck-Brouwer, E Rudy Boersma, Mijna Hadders-Algra

Affiliations

PMID: 16876396
DOI: 10.1016/j.plefa.2006.05.010

Abstract

Homo sapiens has evolved on a diet rich in alpha-linolenic acid C18:3 n3 (short omega3) and long chain polyunsaturated fatty acids (LCP). We have, however, gradually changed our diet from about 10,000 years ago and accelerated this change from about 100 to 200 years ago. The many dietary changes, including lower intake of omega3-fatty acids, are related to 'typically Western' diseases. After a brief introduction in essential fatty acids (EFA), LCP and their functions, this contribution discusses our present low status of notably LCP omega3 in the context of our rapidly changing diet within an evolutionary short time frame. It then focuses on the consequences in pregnancy, lactation and neonatal nutrition, as illustrated by some recent data from our group. We discuss the concept of a 'relative' EFA/LCP deficiency in the fetus as the outcome of high transplacental glucose flux. This flux may in the fetus augment de novo synthesis of fatty acids, which not only dilutes transplacentally transported EFA/LCP, but also causes competition of de novo synthesized oleic acid ( C18:1n9) with linoleic acid for delta-6 desaturation. Such conditions were encountered by us in mothers with high body mass indices, diabetes mellitus and preeclampsia. The unifying factor might be compromised glucose homeostasis. In search of the milk arachidonic acid (AA, C20:4n6) and docosahexaenoic acid (DHA, C22:6n3) contents of our African ancestors, we investigated women in Tanzania with high intakes of freshwater fish as only animal lipid source. These women had milk AA and DHA contents that were well above present recommendations for infant formulae. Both studies stimulate rethinking of 'optimal homeostasis'. Subtle signs of dysbalanced maternal glucose homeostasis may be important and observations from current Western societies may not provide us with an adequate basis for dietary recommendations.

Essentiellit rasvahapot AA, EPA ja DHA solukalvoissa.

AA, C20:4 omega6 (Eicosatetraeenihappo eli arakidonihappo C20:4 omega 6 linjasta on lähtöaine eikosanoideille. Linolihappo (LA) kasvikunnasta johtaa tähän arakidonihappoon kehoentsyymien avulla.

EPA, C20:5 (eicosapentaeenihappo) omega 3 linjasta. Alfa-linoleenihappo (ALA) kasvikunnasta johtaa tähän EPA:5 rasvahappoon.

DHA, C22:6 omega 3 linjasta. Docosahexaeenihappoa muodustuu jatkossa ihmiskehon entsyymeilä .

omega 6 linjasta. Myös kalarasvoista saa näitä pitkiä rasvahappoja valmiina EPA ja DHA muotoa.

Tiedetään, että ihmisen kaikki solut, joissa vain on membraaneja, keräävät membraanin lipidirakenteeseen arakidonihappoa (C20:4), koska se on lähtöaine solun monissa funktioissa ja varsinkin kudosten korjaantumisissa ja immuunivasteessa. Entä sitten paralleelin omega3-linjan rasvahappojen merkitys? Niitäkin solumembraanin fosfolipidit(PL) keräävät rakenteeseensa ja tämä rasvahappojen valinta fosfolipidirakenteeseen on solu- ja kudosspesifistä. Koska nämä kolme pitkää tärkeää essentielliä rakennetta ovat hieman erilaisia ja koska niiden kertymiseen vaikuttaa dieetin antamat essentiellit linjaa muodostavat alkumuodot kuten linolihapon (C18:2 omega 6) ja alfalinoleenihapon (C18:3 omega 3) saanti, niin mitä tiedeään membraaniaanirakennevaikutuksesta?

. 2021;62:100106.

doi: 10.1016/j.jlr.2021.100106. Epub 2021 Aug 13.

EPA and DHA containing phospholipids have contrasting effects on membrane structure

Samuel C R Sherratt¹, Rebecca A Juliano², Christina Copland², Deepak L Bhatt³, Peter Libby³, R Preston Mason⁴

Affiliations

PMID: 34400132
PMCID: PMC8430377
DOI: 10.1016/j.jlr.2021.100106

Free PMC article

Abstract

Omega-3 FAs EPA and DHA influence membrane fluidity, lipid rafts, and signal transduction. A clinical trial, Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial, demonstrated that high-dose EPA (4 g/d icosapent ethyl) reduced composite cardiovascular events in statin-treated high-risk patients. EPA benefits correlated with on-treatment levels, but similar trials using DHA-containing formulations did not show event reduction. We hypothesized that differences in clinical efficacy of various omega-3 FA preparations could result from differential effects on membrane structure. To test this, we used small-angle X-ray diffraction to compare 1-palmitoyl-2-eicosapentaenoyl-sn-glycero-3-phosphocholine (PL-EPA), 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PL-DHA), and 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PL-AA) in membranes with and without 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol. Electron density profiles (electrons/Å³ vs. Å) were used to determine membrane structure, including membrane width (d-space). PL-EPA and PL-DHA had similar membrane structures without POPC and/or cholesterol but had contrasting effects in the presence of POPC and cholesterol. PL-EPA increased membrane hydrocarbon core electron density over an area of ±0-10 Å from the center, indicating an extended orientation. PL-DHA increased electron density in the phospholipid head group region, concomitant with disordering in the hydrocarbon core and a similar d-space (58 Å). Adding equimolar amounts of PL-EPA and PL-DHA produced changes that were attenuated compared with their separate effects. PL-AA increased electron density centered ±12 Å from the membrane center. The contrasting effects of PL-EPA, PL-DHA, and PL-AA on membrane structure may contribute to differences observed in the biological activities and clinical actions of various omega-3 FAs.

Keywords: X-ray diffraction; arachidonic acid; docosahexaenoic acid; eicosapentaenoic acid; membrane structure; omega-3 FAs.

https://pubmed.ncbi.nlm.nih.gov/27718370/

lördag 2 maj 2020

C16.-ceramidi ja sfingosiini-1-fosfaatti (S1P) rintasyöpäsolun proliferaatiossa

Abstract Recently, sphingolipid derivatives, such as ceramide and sphingosine‑1‑phosphate (S1P), have emerged as key modulators in apoptotic cell death and cell proliferation.
This study aimed to clarify the underlying signaling pathways of ceramide and S1P involved in breast cancer cell proliferation.
Ceramide acyl chain length is determined by six mammalian ceramide synthases (CerS). We overexpressed CerS1 to 6 in MCF‑7 cells to examine whether ceramide signaling propagation varies as a function of acyl chain length.
Among the six CerS, only CerS6 overexpression reduced phosphorylation of Akt, S6 kinase (S6K), and extracellular signal‑regulated kinases (ERK) as shown by western blotting.
In addition, CerS6 overexpression reduced MCF‑7 cell proliferation. This effect was partially reversed by co‑treatment with MHY1485, an activator of mammalian target of rapamycin (mTOR), demonstrating an important role for the mTOR pathway in the CerS6‑mediated decrease in MCF‑7 cell proliferation. ERK inhibition, but not Akt inhibition, along with mTOR inhibition synergistically reduced MCF‑7 cell proliferation as measured by MTT assay.
Notably, the expression of CerS6 and S1P receptor 2 (S1PR2), or CerS6 and sphingosine kinase 1 (SphK1), were negatively correlated according to the invasive breast carcinoma patient cohort in The Cancer Genome Atlas database.
In addition, both SphK1 overexpression and S1P addition increased mTOR phosphorylation as shown by ELISA, while S1PR2 inhibition had the inverse effect. These data suggest that CerS6 and SphK1 regulate mTOR signaling in breast cancer cell proliferation. Moreover, mTOR activity can be regulated by the balance between S1P and C16‑ceramide, which is generated by CerS6.

PMID:: 30226616
DOI:: 10.3892/or.2018.6689

[Indexed for MEDLINE]

Sinkkisormiproteiini ZDHHC5 osallistuu S1P :n reseptorin S1PR syklin säätelyyn

https://www.ncbi.nlm.nih.gov/gene/25921

Official Symbol: ZDHHC5
Official Full Name: zinc finger DHHC-type palmitoyltransferase 5
Also known as: DHHC5; ZNF375
Expression: Ubiquitous expression in esophagus (RPKM 30.1), thyroid (RPKM 23.7) and 25 other tissues See more

Preferred Names: palmitoyltransferase ZDHHC5

Names: DHHC-5; membrane-associated DHHC5 zinc finger protein; probable palmitoyltransferase ZDHHC5; zinc finger DHHC domain-containing protein 5; zinc finger DHHC-type containing 5; zinc finger protein 375; zinc finger, DHHC domain containing 5

fredag 3 januari 2020

Rintasyöpä , C16- cer ja S1P keskiössä, mahdollisesti uusia terapiakohteita .

https://www.ncbi.nlm.nih.gov/pubmed/30226616

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2018 Nov;40(5):2977-2987. doi: 10.3892/or.2018.6689. Epub 2018 Sep 7.

C16‑ceramide and sphingosine 1‑phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation.

Kim MH¹, Park JW², Lee EJ³, Kim S⁴, Shin SH², Ahn JH², Jung Y⁵, Park I⁶, Park WJ³.

Author information

Abstract

Recently, sphingolipid derivatives, such as ceramide and sphingosine‑1‑phosphate (S1P), have emerged as key modulators in apoptotic cell death and cell proliferation. This study aimed to clarify the underlying signaling pathways of ceramide and S1P involved in breast cancer cell proliferation. Ceramide acyl chain length is determined by six mammalian ceramide synthases (CerS). We overexpressed CerS1 to 6 in MCF‑7 cells to examine whether ceramide signaling propagation varies as a function of acyl chain length. Among the six CerS, only CerS6 overexpression reduced phosphorylation of Akt, S6 kinase (S6K), and extracellular signal‑regulated kinases (ERK) as shown by western blotting. In addition, CerS6 overexpression reduced MCF‑7 cell proliferation. This effect was partially reversed by co‑treatment with MHY1485, an activator of mammalian target of rapamycin (mTOR), demonstrating an important role for the mTOR pathway in the CerS6‑mediated decrease in MCF‑7 cell proliferation. ERK inhibition, but not Akt inhibition, along with mTOR inhibition synergistically reduced MCF‑7 cell proliferation as measured by MTT assay. Notably, the expression of CerS6 and S1P receptor 2 (S1PR2), or CerS6 and sphingosine kinase 1 (SphK1), were negatively correlated according to the invasive breast carcinoma patient cohort in The Cancer Genome Atlas database. In addition, both SphK1 overexpression and S1P addition increased mTOR phosphorylation as shown by ELISA, while S1PR2 inhibition had the inverse effect. These data suggest that CerS6 and SphK1 regulate mTOR signaling in breast cancer cell proliferation. Moreover, mTOR activity can be regulated by the balance between S1P and C16‑ceramide, which is generated by CerS6

Keramidisyntaasit (CERS) ja sfingolipidien keramidien rasvahappopituuksien (N-acyl chain length) määrytyminen

https://www.ncbi.nlm.nih.gov/pubmed/29632068/
2018 Jun 22;293(25):9912-9921. doi: 10.1074/jbc.RA118.001936. Epub 2018 Apr 9.

Eleven residues determine the acyl chain specificity of ceramide synthases.

Tidhar R¹, Zelnik ID¹ et al. Abstract

Lipids display large structural complexity, with ∼40,000 different lipids identified to date, ∼4000 of which are sphingolipids. A critical factor determining the biological activities of the sphingolipid, ceramide, and of more complex sphingolipids is their N-acyl chain length, which in mammals is determined by a family of six ceramide synthases (CerS). Little information is available about the CerS regions that determine specificity toward different acyl-CoA substrates. We previously demonstrated that substrate specificity resides in a region of ∼150 residues in the Tram-Lag-CLN8 domain. Using site-directed mutagenesis and biochemical analyses, we now narrow specificity down to an 11-residue sequence in a loop located between the last two putative transmembrane domains (TMDs) of the CerS.
The specificity of a chimeric protein, CerS5^{(299-309→CerS2)}, based on the backbone of CerS5 (which generates C16-ceramide), but containing 11 residues from CerS2 (which generates C22-C24-ceramides), was altered such that it generated C22-C24 and other ceramides.
Moreover, a chimeric protein, CerS4^{(291-301→CerS2)}, based on CerS4 (which normally generates C18-C22 ceramides) displayed significant activity toward C24:1-CoA.
Additional data supported the notion that substitutions of these 11 residues alter the specificities of the CerS toward their cognate acyl-CoAs.

Our findings may suggest that this short loop may restrict adjacent TMDs, leading to a more open conformation in the membrane, and that the CerS acting on shorter acyl-CoAs may have a longer, more flexible loop, permitting TMD flexibility. In summary, we have identified an 11-residue region that determines the acyl-CoA specificity of CerS. © 2018 Tidhar et al.

KEYWORDS: ceramide (Cer) ; ceramide synthase (CERS) ; lipid; membrane; sphingolipid

DOI:: 10.1074/jbc.RA118.001936

Free PMC Article

http://www.jbc.org/content/293/25/9912

keramidien rasvahappopituuksien määräytyminen keramidisyntaasilla on kartoitettu 2018 aikoihin. On kuusi keramidisyntaasia. Israelissa ollaan tästä kiinnostuneita.

Suomennosta artikkelista 3.1. 2019:

LIPIDEILLA on laaja rakenteellinen kompleksisuutensa . Näihin mennessä on tunnistettu noin 40 000 erilaista lipidiä ja niistä kuuluu sfingolipidien luokkaan noin 4000 .
Kriittisenä tekijänä sfingolipidien, keramidien ja monimutkaisempien sfingolipidien biologisessa aktiivisuudessa on niiden aktivoituneiden N-rasvahappojen (N-Acyl CoA) pituus; imettäväisissä se määräytyy keramidisyntaasientsyymien avulla (CERS-perhe) Ihmisellä on kuusi CERS- entsyymiä CERS1- CERS6.
On olemassa vain vähän informaatiota siitä, mitkä CERS- entsyymin kohdat määrittävät spesifisyyden eri rasvahappo-CoA- substraatteja kohtaan.
Aiemmin tämä tutkijaryhmä on osoittanut, että substraattispesifisyys on Tram- Lag-CLN8 domaanin 150:n aminohapon kohdalla.
Käyttämällä kohdennettua mutageneesiä ja biokemiallisia analyysejä he nyt kaventavat spesifisyyden 11 aminohapon sekvenssiin eräässä silmukassa, joka sijaitsee kahden transmembraanisen domeenin (TMD) välissä keramidisyntaasissa (CERS) .

C16-keramidikokoa tuottavan CERS5 runkoon perustuva kimeerinen CerS5( 299-309 jakso-CerS2::sta). jossa on myös 11 aminohappoa CERS2 entsyymistä (joka taas tuottaa C22- C24 keramideja), aiheutti sellaisen muuntumisen CERS-spesifisyyteen, että tuottui C22- C24 - ja muita keramideja.

Lisäksi sellainen CERS4- perusteinen keramidisyntaasi ( jotka tuottaa normaalisti C18-C22 keramideja) muutettuna kimeeriseksi proteiiniksi CERS(291-301 jakso CERS2:sta) , osoittaa merkitsevää spesifisyyttä aktiivoitua C24:1- rasvahappoa (C24:1-CoA) kohtaan.

Lisätiedot tukevat havaintoa niden 11 aminohapon kyvystä muuntaa CERS entsyymien spesifisyyksiä niille tyypillisiä aktivoituja rasvahappoja kohtaan. Tutkijoiden havainnot viittanevat siihen, että tämä lyhyt silmukka rajoittanee toisiaan lähellä olevia transmembraanisia domaaneja (TMD) johtaen kalvon avoimempaan konfrontaatioon ja ne CERS entsyymit, jotka vaikuttavat lyhyehköihin aktivoituneisiin rasvahappoihin saattavat omata pidempiä, taipuvaisempia silmukoita sallien transmembraanidomaaneille joustoa. Yhteenvetona tutkijat ovat tunnistaneet 11 aminohapon alueen, joka määrittää CERS entsyymin spesifisyyden aktiivia rasvahappoa kohtaan.

Keramidisyntaasit 1-6 , CERS1- CERS6

CERS1(19p13.11) , EPM8, GDF1, LAG1, UOG1, GDF-1, LASS1.

Tämä entsyymi tuottaa C18-keramideja aivojen neuroneissa. Jos geenin ilmentymä on koholla se merkitse neuronin pitkäikäisyyttä, kuntaas alentunut ilmenemä assosioituu myoklooniseen epilepsiaan. ja dementiaan ihmisessä.

https://www.ncbi.nlm.nih.gov/gene/10715

Official Symbol: CERS1
Official Full Name: ceramide synthase 1

Also known as: EPM8; GDF1; LAG1; UOG1; GDF-1; LASS1
Summary: This gene encodes a ceramide synthase enzyme, which catalyzes the synthesis of ceramide, the hydrophobic moiety of sphingolipids. The encoded enzyme synthesizes 18-carbon (C18) ceramide in brain neurons. Elevated expression of this gene may be associated with increased longevity, while decreased expression of this gene may be associated with myoclonus epilepsy with dementia in human patients. This protein is transcribed from a monocistronic mRNA as well as a bicistronic mRNA, which also encodes growth differentiation factor 1. [provided by RefSeq, Jul 2016]
Expression: Biased expression in brain (RPKM 22.5) and testis (RPKM 5.1).

Preferred Names: ceramide synthase 1

Names: Embryonic growth/differentiation factor 1; (EPM8); longevity assurance (LAG1, S. cerevisiae) homolog 1; longevity assurance gene 1 protein homolog 1 (LASS1); protein UOG-1; upstream of GDF1; (UOG1)

CERS2 (1q21.3), TMSG1 ( Tuumormetastasis-suppressor gene 1 protein )

h ttps://www.ncbi.nlm.nih.gov/gene/29956

Also known as: L3; LASS2; SP260; TMSG1
Summary: This gene encodes a protein that has sequence similarity to yeast longevity assurance gene 1. Mutation or overexpression of the related gene in yeast has been shown to alter yeast lifespan. The human protein may play a role in the regulation of cell growth. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in liver (RPKM 113.9), adrenal (RPKM 85.4) and 25 other tissues See more
Preferred Names: ceramide synthase 2

Names: LAG1 homolog, ceramide synthase 2; LAG1 longevity assurance 2; longevity assurance (LAG1, S. cerevisiae) homolog 2; sphingosine N-acyltransferase CERS2; tumor metastasis-suppressor gene 1 protein

( 299-309 aminohapot : FFGYYFFNSMM

ff
      301 gyyffnsmm)

CERS3 (5q21.3),

https://www.ncbi.nlm.nih.gov/gene/204219

Also known as: ARCI9; LASS3
Summary: This gene is a member of the ceramide synthase family of genes. The ceramide synthase enzymes regulate sphingolipid synthesis by catalyzing the formation of ceramides from sphingoid base and acyl-coA substrates. This family member is involved in the synthesis of ceramides with ultra-long-chain acyl moieties (ULC-Cers), important to the epidermis in its role in creating a protective barrier from the environment. The protein encoded by this gene has also been implicated in modification of the lipid structures required for spermatogenesis. Mutations in this gene have been associated with male fertility defects, and epidermal defects, including ichthyosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
Expression: Biased expression in skin (RPKM 15.5), esophagus (RPKM 13.5) and 1 other tissue See more
Preferred Names: ceramide synthase 3

Names: LAG1 homolog, ceramide synthase 3; LAG1 longevity assurance homolog 3; dihydroceramide synthase 3; sphingosine N-acyltransferase CERS3

NM_001290341.2 → NP_001277270.1 ceramide synthase 3 isoform 1

CERS4 (19p13.2),

https://www.ncbi.nlm.nih.gov/gene/79603

Also known as: Trh1; LASS4
Expression: Ubiquitous expression in thyroid (RPKM 13.9), prostate (RPKM 10.3) and 24 other tissues See more
Orthologs: mouse all

CERS5 (12q13.12),

https://www.ncbi.nlm.nih.gov/gene/91012

Also known as: Trh4; LASS5
Summary: This gene encodes a protein that belongs to the TLC (TRAM, LAG1 and CLN8 homology domains) family of proteins. The encoded protein functions in the synthesis of ceramide, a lipid molecule that is involved in a several cellular signaling pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
Expression: Ubiquitous expression in endometrium (RPKM 6.0), placenta (RPKM 5.6) and 25 other tissues See more
Preferred Names: ceramide synthase 5

Names: LAG1 homolog, ceramide synthase 5; LAG1 longevity assurance homolog 5; TRAM homolog 4; sphingosine N-acyltransferase CERS5

NM_001281731.1 → NP_001268660.1 ceramide synthase 5 isoform 2

2008 Sep 26;283(39):26509-17. doi: 10.1074/jbc.M801597200. Epub 2008 Aug 1.

Ceramide generated by sphingomyelin hydrolysis and the salvage pathway is involved in hypoxia/reoxygenation-induced Bax redistribution to mitochondria in NT-2 cells.

Jin J¹, Hou Q, Mullen TD,et al.

CERS6 (2q24.3),

https://www.ncbi.nlm.nih.gov/gene/253782

Also known as: CERS5; LASS6
Expression: Ubiquitous expression in colon (RPKM 18.1), thyroid (RPKM 16.4) and 25 other tissues See more

Preferred Names: ceramide synthase 6

Names: LAG1 homolog, ceramide synthase 6; longevity assurance homolog 6

NM_001256126.2 → NP_001243055.1 ceramide synthase 6 isoform 1.

TRAM, LAG1 and CLN8: members of a novel family of lipid-sensing domains?Trends Biochem. Sci. 2002 Aug ; 27(8):381-3

The human CERS6 gene promoter harbors a large CpG island (94 CpGs) and multiple transcription factor binding sites (TFBS), which support precise transcriptional regulation and signaling functions

Additional regulation is conferred by 15 microRNA
            (miRNA) target sites identified in the CERS6 3'-UTR region
            Publication Status: Online-Only

 JOURNAL   FASEB J. 24 (1), 296-308 (2010)
   PUBMED   19723703
  REMARK    GeneRIF: Mechanistically, regulation of ER-stress-induced apoptosis
            by CerS6/C(16)-ceramide was linked to the activation of a specific
            arm, ATF6/CHOP, of the unfolded protein response pathway.

https://www.ncbi.nlm.nih.gov/pubmed/26887952

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tisdag 7 mars 2023

Pitkäketjuisten essentiellien rasvahappojen osuudet nykyajan dieeteissä

Long-chain polyunsaturated fatty acids in maternal and infant nutrition

Essentiellit rasvahapot AA, EPA ja DHA solukalvoissa.

EPA and DHA containing phospholipids have contrasting effects on membrane structure

lördag 2 maj 2020

C16.-ceramidi ja sfingosiini-1-fosfaatti (S1P) rintasyöpäsolun proliferaatiossa

Sinkkisormiproteiini ZDHHC5 osallistuu S1P :n reseptorin S1PR syklin säätelyyn

fredag 3 januari 2020

Rintasyöpä , C16- cer ja S1P keskiössä, mahdollisesti uusia terapiakohteita .

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C16‑ceramide and sphingosine 1‑phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation.

Author information

Abstract

Keramidisyntaasit (CERS) ja sfingolipidien keramidien rasvahappopituuksien (N-acyl chain length) määrytyminen

Eleven residues determine the acyl chain specificity of ceramide synthases.

KEYWORDS: ceramide (Cer) ; ceramide synthase (CERS) ; lipid; membrane; sphingolipid

Keramidisyntaasit 1-6 , CERS1- CERS6

CERS1(19p13.11) , EPM8, GDF1, LAG1, UOG1, GDF-1, LASS1.

Tämä entsyymi tuottaa C18-keramideja aivojen neuroneissa. Jos geenin ilmentymä on koholla se merkitse neuronin pitkäikäisyyttä, kuntaas alentunut ilmenemä assosioituu myoklooniseen epilepsiaan. ja dementiaan ihmisessä.

CERS2 (1q21.3), TMSG1 ( Tuumormetastasis-suppressor gene 1 protein )

( 299-309 aminohapot : FFGYYFFNSMM

CERS3 (5q21.3),

CERS4 (19p13.2),

CERS5 (12q13.12),

CERS6 (2q24.3),

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