6.2.2018,10:20.Sana psalmista 86:15,16.
(A Maskil of Ethan the Ezrahite) Blessed are the people who know the festal shout, who walk , o Lord, in the light of thy countenance;who exult in thy name all the day, and extol thy righteousness.
tisdag 6 februari 2018
tisdag 23 januari 2018
OXER1 reseptorista tietoja
Tietoja OXER1 reseptorista PubMed hakulaiteella tietueesta :
Otan yhden artikkelin sitaattina: Siitä käy ilmi että OXER1 -reseptoriin vastavaikuttaa omega3-linjasta tuleva DHA*, dokosahexaeenihappo eli kalarasvoissa oleva pitkäketjuinen rasvahappo. Merkkaan tähdellä tämän lauseen:
Mol Cell Endocrinol. 2013 May 22;371(1-2):71-8. doi: 10.1016/j.mce.2012.11.003. Epub 2012 Nov 16.
Expression and function of OXE receptor, an eicosanoid receptor, in steroidogenic cells.
Abstract
Hormonal
regulation of steroidogenesis involves arachidonic acid (AA) metabolism
through the 5-lipoxygenase pathway. One of the products,
5-hydroperoxy-eicosatetraenoic acid (5-HpETE), acts as a modulator of
the activity of the steroidogenic acute regulatory (StAR) protein
promoter. Besides, an oxoeicosanoid receptor of the leukotriene receptor
family named OXE-R is a membrane protein with high affinity and
response to 5-HpETE, among other AA derivatives.
- The aim of our work was to elucidate whether this receptor may be involved in steroidogenesis. RT-PCR and western blot analysis demonstrated the presence of the mRNA and protein of the receptor in human H295R adrenocortical cells. The treatment of H295R or MA-10 cells (murine Leydig cell line) with 8Br-cAMP together with docosahexaenoic acid (DHA*, an antagonist of the receptor) partially reduced StAR induction and steroidogenesis. On the contrary, 5-oxo-ETE - the prototypical agonist, with higher affinity and potency on the receptor - increased cAMP-dependent steroid production, StAR mRNA and protein levels. These results lead us to conclude that AA might modulate StAR induction and steroidogenesis, at least in part, through 5-HpETE production and activation of a membrane receptor, such as the OXE-R.
- PMID:
- 23159987
- DOI:
- 10.1016/j.mce.2012.11.003
Mead haposta engl. tekstiä
Mead acid is an omega-9 fatty acid, first characterized by James F. Mead.[1] As with some other omega-9 polyunsaturated fatty acids, animals
Wikipedian englantilaisesta versiosta löytyy enemmänkin matabolista kartata Meadin haposta
yleensä syklo-oxygenaasientsyymit otavat substraatikseen arakidonihapon kun oksidoivat tulehduksissa siitä vaikuttavia aineita,kuten PGH2 prostaglandiinia H2. Meadin happo muistuttaa arakidonia sikäli että siinä on 20 hiiltä ja ainakin 3 kaksoissidosta, joten se tarjoaa sellaista rakennetta, jota entsyymi voi käyttää arakidonihapon puutteessa. Meadin happo voi konvertoitua leukotrieeneksi LTC3 ja LTD3.
Myös entyymi 5-lipoxygenaasi voi modifioida Meadin happoa ja tekee siitä 5-hydroxy-eikosatrieenihappoa (5-HETrE).
Entsyymi 5-hydroxyeikosanoididehydrogenaasi voi muuttaa sen sitten 5-oxoeikosatrieenihapoksi (5-oxo-ETrE). Tämä metaboliitti taas on yhtä vahva vaikuttaja kuin sen arakidonihaposta tullut analogi 5-oxoeikosatetraeenihappo (5-oxo-ETE). Tässä vertaillaan niiden vaikutusta stimuloida ihmisen veren eosinofiilejä ja neutrofiilejä. On ilmeistä että Meadin haposta tuleva 15-oxo-ETrE käyttää samaa reseptoria kuin arakidonihaposta tuleva analogi: nimittäin reseptoria OXER1 ja ehkä sen takia se on kuin analoginsa , ihmisen allergisten ja inflammatoristen reaktioiden välittäjä.
Role in inflammation
Cyclooxygenases are enzymes known to play a large role in inflammatory processes through oxidation of unsaturated fatty acids. Most notably, the formation of prostaglandin H2 from arachidonic acid which is very similar in structure to mead acid. When physiological levels of arachidonic acid are low, other unsaturated fatty acids including mead and linoleic acid are oxidized by COX.Mead acid is also converted to leukotrienes C3 and D3.[8]
Mead acid is metabolized by 5-lipoxygenase to 5-hydroxyeicosatrieonic acid (5-HETrE)[9] and then by 5-Hydroxyeicosanoid dehydrogenase to 5-oxoeicosatrienoic acid (5-oxo-ETrE).[10] 5-Oxo-ETrE is as potent as its arachidonic acid-derived analog, 5-oxo-eicosatetraenoic acid (5-oxo-ETE), in stimulating human blood eosinophils and neutrophils;[11] it presumably does so by binding to the 5-oxo-ETE receptor (OXER1) and therefore may be, like 5-oxo-ETE, a mediator of human allergic and inflammatory reactions
- Tietoja OXER1 reseptorista.
OXER1-reseptorin sijainti on kromosomissa 2p21. Se on g-proteiiniin kytkeytynyt rseptori 170 (GPR170) ja se on pääasiassa arakidonihaposta johtuvan karboksyylihappometaboliitin 5-HETEpääasiallinen reseptori.
Mielenkiintoinen kappale! Kuitenkin lopuksi sanotaan että tiedot ovat toistaiseksi prekliinisiä.
Oxoeicosanoid receptor 1 (OXER1) also known as G-protein coupled receptor 170 (GPR170) is a protein that in humans is encoded by the OXER1 gene located on human chromosome 2p21; it is the principle receptor for the 5-Hydroxyicosatetraenoic acid family of carboxy fatty acid metabolites derived from arachidonic acid.[3][4][5] The receptor has also been termed hGPCR48, HGPCR48, and R527 but OXER1 is now its preferred designation
To date, however, all studies have been pre-clinical; they use model systems that can suggest but not prove the contribution of OXER1 to human physiology and diseases. The most well-studied and promising area for OXER1 function is in allergic reactions. The recent development of OXER1 antagonists will help address this issue.
Omega9-linjasta Meadin happo
https://fi.wikipedia.org/wiki/Meadin_happo
Meadin happo eli (5Z,8Z,11Z)-eikosa-5,8,11-trieenihappo eli 20:3(n-9) on monityydyttymätön omega-9-rasvahappo, jonka kemiallinen kaava on C20H34O2, moolimassa 306,48276 g/mol ja CAS-numero 20590-32-3.
Yhdiste on saanut nimensä James F. Meadin mukaan. Meadin happoa syntyy oleiinihapon reagoidessa nisäkkäiden aineenvaihdunnassa ja sitä on löydetty verestä ja rustosta. Meadin happoa käytetään C3 ja D3 leukotrieenien aiheuttaman tulehdusten pilkkomiseen.
sitten 20:2 (n-9),
sitten 20:3 (n-9),
sitten 22:3 (n-9).
Meadin happo eli (5Z,8Z,11Z)-eikosa-5,8,11-trieenihappo eli 20:3(n-9) on monityydyttymätön omega-9-rasvahappo, jonka kemiallinen kaava on C20H34O2, moolimassa 306,48276 g/mol ja CAS-numero 20590-32-3.
Yhdiste on saanut nimensä James F. Meadin mukaan. Meadin happoa syntyy oleiinihapon reagoidessa nisäkkäiden aineenvaihdunnassa ja sitä on löydetty verestä ja rustosta. Meadin happoa käytetään C3 ja D3 leukotrieenien aiheuttaman tulehdusten pilkkomiseen.
Aiheesta muualla kts linkit.
Kommenttini: Katso kuvaa:
Kuten huomaa, rasvahapon "häntäosa" on pidempi kuin omega6 ja omega3 sarjassa. Se onkin omega9 sarjaa, eli siinä on 9 hiiliatomia ennen kuin tulee kaksoissidoksista ensimmäinen päädystä lukien. Oliviöljyä käytettäessä siinä olevasta öljyhaposta C18:1(n-9), muodostuu tällaista desaturaasi- ja elongaasientyymeillä kehossa.
Ensin18:2 (n-9);sitten 20:2 (n-9),
sitten 20:3 (n-9),
sitten 22:3 (n-9).
Ne entsyymit jotka muokkaavat n-6 ja n-3 sarjasta aineenvaihdunnallisia tuotteita kuten leukotrieenejä (voivat muodostaa tästä 20:3 (n-9) kokoisesta metaboliitista LT3 leukotrieeniä. (omega6 sarjan leukotrieenit ovat LT4- sarjaa ja omega-3 sarjasta tulevat leukotrieenit LT5-sarjaa). Tiedetään että LT4 sarjasta tulee kliinisesrti aggressiivisia leukotrieenejä LT4 lajeja ( 20 hiilen eikosanoideja) . Nämä n9- ja n3 sarjan leukotrieenit LT3 ja LT5 voivat voivat tehdä interaktiota sen aggressiivisuuteen ja niillä voi olla joitain aivan omia vaikutuksiaan, kun niitä vain löytää kirjallisuudesta.
Henkilökohtaisesti olen nyt kiinnostunut siitä, miten tämän 9n-sarjan tuotteet degradoituvat.
- PubChem: Mead acid (englanniksi)
- Human Metabolome Database: 5,8,11-Eicosatrienoic acid (englanniksi)
måndag 22 januari 2018
Rasvametaboliittien osuus syövässä
http://www.aimspress.com/article/10.3934/genet.2017.2.103/fulltext.html
Fabrizio Gentile1,
Alessia Arcaro1,
Stefania Pizzimenti2,
Martina Daga2,
Giovanni Paolo Cetrangolo1,
Chiara Dianzani3,
Alessio Lepore4,
Maria Graf4,
Paul R. J. Ames5,
Giuseppina Barrera2, 
, 
DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity
,
1 Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Campobasso, Italy
2 Department of Clinical and Biological Sciences, University of Torino, Torino, Italy
3 Department of Drug Science and Technology, University of Torino, Torino, Italy
4 Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy
5 CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal, and Department of Haematology, Dumfries Royal Infirmary, Dumfries, Scotland, UK
2 Department of Clinical and Biological Sciences, University of Torino, Torino, Italy
3 Department of Drug Science and Technology, University of Torino, Torino, Italy
4 Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy
5 CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal, and Department of Haematology, Dumfries Royal Infirmary, Dumfries, Scotland, UK
- Otan talteen lyhennykset, koska ne voivat antaa hakusanoja
Abbreviations and symbols
AA: arachidonic acid, 5, 8, 11, 14-eicosatetraenoic acid
ADHs: alcohol dehydrogenases
ALA: alpha-linolenic acid, 9, 12, 15-octadecatrienoic acid
ALDHs: Aldehyde dehydrogenases
ANA: antinuclear autoantibodies
APCs: antigen-presenting cells
AR: aldose reductase
BSA: bovine serum albumin
1, N6-ε-dAde: 1, N6-etheno-2'-deoxyadenosine
dAde: deoxyadenosine
DAMPs: damage-associated molecular patterns
DCs: dendritic cells
dCyt: deoxycytidine
ε-dCyt: 3, N4-etheno-2'-deoxycytidine
N2-dGuo: N2-propano-2'-deoxyguanosine
dGuo: deoxyguanosine
1, N2-ε-dGuo: 1, N2-etheno-2'-deoxyguanosine
dsDNA, double-strand DNA
N2, 3-ε-dGuo: N2, 3-etheno-2'-deoxyguanosine
EHN: 2, 3-epoxy-4-hydroxy-nonanal
DHA: 4, 7, 10, 13, 16, 19-docosahexanoic acid
GPX2: glutathione peroxidase 2
GAPDH: glyceraldehyde-3-phosphate dehydrogenase
GSTs: glutathione-S-transferases
HCC: hepatocellular carcinoma
HDAC: histone deacetylase
HDL3: high-density lipoprotein 3
HHE: 4-hydroxy-2(E)-hexenal
HNE: 4-hydroxy-2-nonenal
HPHE: 4-hydroperoxy-2(E)-hexenal
HPNE: 4-hydroperoxy-2(E)-nonenal
HSA: human serum albumin
HSP60: heat shock 60 kDa protein 1
HY-RNAs: histidine-rich RNAs
KLH: keyhole limpet hemocyanine
LDLs: low-density lipoproteins
LA: linoleic acid, 9, 12-octadecadienoic acid
LMP1: latent membrane protein-1
LO·: alkoxyl radical
LOO·: lipoperoxyl radical
LOX-1: oxidized low-density lipoprotein receptor 1
LOOH: lipid hydroperoxide
LPO: lipid peroxidation
mAbs: monoclonal antibodies
MDA: malondialdehyde
MSA: murine serum albumin
NAFLD: non-alcoholic fatty liver disease
NASH: non-alcoholic steatohepatitis
Nrf2: NF-E2-related factor 2
NZW: New Zealand White
8-OHdG: 8-hydroxydeoxyguanosine
·OH: hydroxyl radical
OHE: 4-oxo-2(E)-heptenal
ONE: 4-oxo-2(E)-nonenal
oxLDLs: oxidized low-density lipoproteins
OSEs: oxidation-specific epitopes
PRRs: pattern recognition receptors
PUFAs: polyunsaturated fatty acids
RA: rheumatoid arthritis
RLIP76: Ral-interacting protein
RNPs: ribonucleoprotein particles
ROS: reactive oxygen species
SCE: sister chromatide exchange
SLE: systemic lupus erythematosus
SOD2: superoxide dismutase 2
SS: Sjögren syndrome
α-CH3-γ-OH-PdG: α-hmethyl-γ-hydroxy-1, N2-propano-2'-deoxyguanosine
HNE-dGuo: 1, N2-propano-2'-deoxyguanosine adduct of HNE
9(S)-HPODE: 9(S)-hydroperoxy-9, 11-octadecadienoic acid
13(S)-HPODE: 13(S)-hydroperoxy-9, 11-octadecadienoic acid
MAP kinases: mitogen-activated protein kinases
MCL1: induced myeloid leukemia cell differentiation protein Mcl-1
M1dA: N6-(3-oxoprenyl)-deoxyadenosine
M1dC: N4-(3-oxoprenyl)-deoxycytidine
M1dG: malondialdehyde-2'-deoxyguanosine, or pyrimido[1, 2-a]purine-10(3H)-one-2'-deoxyribose
α-OH-PdG: α-hydroxy-1, N2-propano-2'-deoxyguanosine
γ-OH-PdG: γ-hydroxy-1, N2-propano-2'-deoxyguanosine
ONE-dAde: 7-(2"-oxoheptyl)-1, N6-etheno-2'-deoxyadenosine
ONE-dCyt: 7-(2"-oxoheptyl)-3, N4-etheno-2'-deoxycytidine
ONE-dGuo: 7-(2"-oxoheptyl)-1, N2-etheno-2'-deoxyguanosine
OPdG:
N2-(3-oxoprop-1-enyl)-deoxyguanosine
8-oxo-dGuo: 8-oxo-hydroxy-7, 8-dihydro-2'-deoxyguanosine
PdG:
N2-(3-oxopropyl)-deoxyguanosine
PEITC: beta-phenylethyl isothiocyanate
PPAR gamma: peroxisome proliferator-activated receptor gamma
In recent years, it has become evident that lipid peroxidation (LPO)
products are involved in the intracellular signaling mechanisms that
determine the cell's final fate [1].
LPO arises from the oxidation of fatty acids induced by oxidative
stress causing agents, e.g., oxidants, heat shock, UV and X irradiation,
metal storage, excess caloric intake and serum starvation. Oxidative
stress imports increases of reactive oxygen species (ROS) which, in
turn, can affect signaling mechanisms in a concentration-dependent
manner [2].
However, although increased ROS production has been observed in several
human diseases, such as cancer and neurodegenerative diseases, an
increase of LPO products is not always present. This is true in
particular for cancer cells, which often display high levels of
oxidative stress, whereas increased levels of LPO products were present
only in some cancer types, depending on the lipid composition of
cellular membranes, the presence of inflammation and the level of
aldehyde metabolizing enzymes [3,4].
On the contrary, in inflammatory and neurodegenerative diseases the
increases of ROS almost always were accompanied by increases of LPO and,
as a consequence, LPO products.
Several studies have been performed regarding the biological roles played by aldehydes, since they have a prolonged half-life, can diffuse from their sites of formation and react with the surrounding cells. Moreover, the aldehydes can be delivered by the bloodstream and secreted in the urine. To the contrary, free radicals, produced during LPO, have a very short life and can produce only localized effects. For these reasons, the aldehydes have been defined as "second messengers of oxidative stress" [5]. These lipid electrophiles have long been studied, due to their potential to react with nucleophilic functional groups in lipids, proteins, and DNA [6]. The nucleophilic functional groups include sulfhydryl, guanidine, imidazole and amino groups and DNA bases. In particular, the aldehydes often attack the free-NH2− groups of DNA bases to form covalent adducts, which are partially responsible for the biological consequences of LPO in normal physiology and pathophysiology. In this review we summarize the most recent evidence of DNA damage by LPO products in several diseases, such as cancer, inflammation and autoimmunity.
Several studies have been performed regarding the biological roles played by aldehydes, since they have a prolonged half-life, can diffuse from their sites of formation and react with the surrounding cells. Moreover, the aldehydes can be delivered by the bloodstream and secreted in the urine. To the contrary, free radicals, produced during LPO, have a very short life and can produce only localized effects. For these reasons, the aldehydes have been defined as "second messengers of oxidative stress" [5]. These lipid electrophiles have long been studied, due to their potential to react with nucleophilic functional groups in lipids, proteins, and DNA [6]. The nucleophilic functional groups include sulfhydryl, guanidine, imidazole and amino groups and DNA bases. In particular, the aldehydes often attack the free-NH2− groups of DNA bases to form covalent adducts, which are partially responsible for the biological consequences of LPO in normal physiology and pathophysiology. In this review we summarize the most recent evidence of DNA damage by LPO products in several diseases, such as cancer, inflammation and autoimmunity.
Rasvaisen dieetin vaikutus luustoon
Tukevuus sinänsä ei ole niin paha asia, mutta painovakauden menetys on signaali jostain håiriötilasta joka on progredioimassa johonkin suuntaan, arvelen. Ja siltä kannalta voi painon kasvu olla signaali esim alkavasta syövästä. Tässä aksotaan mikä suhde rasvaisella ravinnolla on luun muodostukseen. ei erityisempää korrelaatiota,.
LÄHDE: https://www.ncbi.nlm.nih.gov/pubmed/29188898
LÄHDE: https://www.ncbi.nlm.nih.gov/pubmed/29188898
J Nutr Health Aging. 2017;21(10):1337-1343. doi: 10.1007/s12603-017-0871-x.
Influence of High-Fat Diet on Bone Tissue: An Experimental Study in Growing Rats.
Rezende Yanagihara G1, Carminati Shimano R, Atsuko Tida J, Suzuki Yamanaka J, Yasuyo Fukada S, Mardegan Issa JP, Shimano AC, Tavares JM.
Abstract
BACKGROUND:
The relationship between obesity and bone tissue remains contradictory, especially when the effect of high-fat diet is assessed in experimental models. The aim of this study was to evaluate the effects of high-fat diet on bone metabolism of growing rats.
METHODS:
Twenty weaned female Wistar rats were equally divided into two groups: SD (standard diet) and HFD (high-fat diet with 60 % of energy as fat). After five weeks of the two diets, the rats were euthanized, and the liver, blood and bones extracted. The liver was analysed for malondialdehyde (MDA) and reduced glutathione (GSH) concentrations. Blood was analysed by the ELISA method for osteoprotegerin (OPG) and tumour necrosis factor ligand superfamily member 11 (TNFSF11/RANKL). The bone tissue was analysed by dual-energy X-ray absorptiometry (DXA), mechanical tests, computed microtomography, histological quantitative analysis and scanning electron microscopy. The gene expressions of PPAR-γ Runx-2, RANKL and Cathepsin-K were also evaluated.
RESULTS:
HFD caused an increase in the MDA concentration, indicating oxidative stress. It also increased the expression of PPAR-γ, which is the gene that is related to adipocyte differentiation. There was an increase in BMD of the tibia of animals fed with the HFD, but other microstructural and mechanical properties were maintained unaltered. In addition, there were no changes in the gene expressions related to the differentiation of osteoblasts and osteoclasts, as well as no changes to the biochemical markers of bone formation and bone resorption.
CONCLUSION:
Liver and gene parameters are changed in response to the HFD. However, although there was an increase in BMD, the microstructure and function of the bone did not change after a 5-week HFD.
The relationship between obesity and bone tissue remains contradictory, especially when the effect of high-fat diet is assessed in experimental models. The aim of this study was to evaluate the effects of high-fat diet on bone metabolism of growing rats.
METHODS:
Twenty weaned female Wistar rats were equally divided into two groups: SD (standard diet) and HFD (high-fat diet with 60 % of energy as fat). After five weeks of the two diets, the rats were euthanized, and the liver, blood and bones extracted. The liver was analysed for malondialdehyde (MDA) and reduced glutathione (GSH) concentrations. Blood was analysed by the ELISA method for osteoprotegerin (OPG) and tumour necrosis factor ligand superfamily member 11 (TNFSF11/RANKL). The bone tissue was analysed by dual-energy X-ray absorptiometry (DXA), mechanical tests, computed microtomography, histological quantitative analysis and scanning electron microscopy. The gene expressions of PPAR-γ Runx-2, RANKL and Cathepsin-K were also evaluated.
RESULTS:
HFD caused an increase in the MDA concentration, indicating oxidative stress. It also increased the expression of PPAR-γ, which is the gene that is related to adipocyte differentiation. There was an increase in BMD of the tibia of animals fed with the HFD, but other microstructural and mechanical properties were maintained unaltered. In addition, there were no changes in the gene expressions related to the differentiation of osteoblasts and osteoclasts, as well as no changes to the biochemical markers of bone formation and bone resorption.
CONCLUSION:
Liver and gene parameters are changed in response to the HFD. However, although there was an increase in BMD, the microstructure and function of the bone did not change after a 5-week HFD.
KEYWORDS:
Bone mineral density; bone quality; obesity; osteoporosis
Bone mineral density; bone quality; obesity; osteoporosis
- PMID:
- 29188898
- DOI:
- 10.1007/s12603-017-0871-x
Tieto malondialdehydistä 1986 eläinkokeista
https://www.ncbi.nlm.nih.gov/pubmed/3713450
1. Tiedetään että lipidiperoksidaatio tuottaa MDA:ta jo dieetin puolella ja sitten kehossa.
2. Sillä on reaktiivisuutta tumahappojen, proteiinien ja fosfolipidien funktionaalisiin ryhmiin,
3. Se on bakteerille mutageeninen.
4. Koe-eläimissä se on ihosyöpää ja maksasyöpää aiheuttava.
Artikkeli kuvaa eläinkokeita, joisa syötettiin malondialdehydin natriumenolisuolaa.se vaikutti maksasolutumien annoksesta riippuvia hyperplastisia ja neoplastisia muutoksia ja nosti mortaliteetin mitä korkeimmalle tasolle aiheutamatta kuitenkaan maksatuumoreita.
Ihofibroblastiviljelmään lisättynä se aiheutti epänormaaliutta tumiin.
(1,3,C14*) -merkattu MDA oxidoitui (C14*) asetaatiksi sekä C*O2 hiilidioksidiksi in vivo nopeasti koeläimen maksan mitokondrioissa. Kuitenkin radioaktiivisuudesta oli havaittavissa 10% virtsasta.
Kromotagrafisesti havaittiin useita tuoteita, joista tuli MDA:ta happohydrolyysissä.
MDA:n kokonaiseritys lisääntyi lipidiperoksidaatiota aiheuttavista seikoista, kuten E-vitamiinin puutteesta, raudasta, hiilitetrakloridista ja kudosten rikastamisesta PUFA-rasvahapoilla.
MDA:n päämetaboliittina virtsassa todettiin N-asetyl-e-(2-propenal)lysiiniä.
Kun MDA reagoi ensisijaisesti ravinnossa tulevien N-terminaalisten lysiinien epsilon-aminoryhmän kanssa, muodostuu yllämainittua tuotetta. Mutta sitä muodsotuu myös kehossa, sillä jos koe-eläimiä pidettiin MDA-vapaalla dieetillä tai paastossa, niin tuota molekyyliä esiintyi kuitenkin virtsassa.
1. Tiedetään että lipidiperoksidaatio tuottaa MDA:ta jo dieetin puolella ja sitten kehossa.
2. Sillä on reaktiivisuutta tumahappojen, proteiinien ja fosfolipidien funktionaalisiin ryhmiin,
3. Se on bakteerille mutageeninen.
4. Koe-eläimissä se on ihosyöpää ja maksasyöpää aiheuttava.
Artikkeli kuvaa eläinkokeita, joisa syötettiin malondialdehydin natriumenolisuolaa.se vaikutti maksasolutumien annoksesta riippuvia hyperplastisia ja neoplastisia muutoksia ja nosti mortaliteetin mitä korkeimmalle tasolle aiheutamatta kuitenkaan maksatuumoreita.
Ihofibroblastiviljelmään lisättynä se aiheutti epänormaaliutta tumiin.
(1,3,C14*) -merkattu MDA oxidoitui (C14*) asetaatiksi sekä C*O2 hiilidioksidiksi in vivo nopeasti koeläimen maksan mitokondrioissa. Kuitenkin radioaktiivisuudesta oli havaittavissa 10% virtsasta.
Kromotagrafisesti havaittiin useita tuoteita, joista tuli MDA:ta happohydrolyysissä.
MDA:n kokonaiseritys lisääntyi lipidiperoksidaatiota aiheuttavista seikoista, kuten E-vitamiinin puutteesta, raudasta, hiilitetrakloridista ja kudosten rikastamisesta PUFA-rasvahapoilla.
MDA:n päämetaboliittina virtsassa todettiin N-asetyl-e-(2-propenal)lysiiniä.
Kun MDA reagoi ensisijaisesti ravinnossa tulevien N-terminaalisten lysiinien epsilon-aminoryhmän kanssa, muodostuu yllämainittua tuotetta. Mutta sitä muodsotuu myös kehossa, sillä jos koe-eläimiä pidettiin MDA-vapaalla dieetillä tai paastossa, niin tuota molekyyliä esiintyi kuitenkin virtsassa.
Lipids. 1986 Apr;21(4):305-7.
The metabolism of malondialdehyde.
Abstract .Interest
in malondialdehyde (MDA) metabolism stems from its formation as a
product of lipid peroxidation in the diet and in the tissues; its
reactivity with functional groups of nucleic acid bases, proteins and
phospholipids; its mutagenicity in bacteria, and its reported skin and
liver carcinogenicity in animals.
Administration of the Na enol salt of
MDA in the drinking water of mice over a range of 0.1-10.0
micrograms/g/day for 12 mo produced dose-dependent hyperplastic and
neoplastic changes in liver nuclei and increased mortality at the
highest level but produced no gross hepatic tumors.
Addition of MDA to the medium of rat skin fibroblasts grown in culture caused nuclear abnormalities at concentrations as low as 10(-6) M despite an uptake of only 4%.
[1,3-14C] MDA was rapidly oxidized to [14C]acetate in rat liver mitochondria and to 14CO2 in vivo; however, approximately 10% of the radioactivity was recovered in the urine.
Chromatographic analysis of rat urine revealed the presence of several compounds which yield MDA on acid hydrolysis.
Total MDA excretion increased in response to conditions which stimulate lipid peroxidation in vivo, including vitamin E deficiency, Fe or CCl4 administration, and enrichment of the tissues with PUFA.
N-acetyl-e-(2-propenal)lysine was identified as a major urinary metabolite of MDA in rat and human urine. This compound is derived primarily from N-alpha-(2-propenal)lysine released in digestion as a product of reactions between MDA and the epsilon-amino groups of N-terminal lysine residues in food proteins. However, its presence in the urine of animals fasted or fed MDA-free diets indicates that it is also formed in vivo.(ABSTRACT TRUNCATED AT 250 WORDS).
Suomennos 22.1. 2018
Kommentti: Käytännössä tämä merkannee sitä,että PUFA- käytöllä on jokin suositeltu ylärajansa joka ehkä on individuelli.
Addition of MDA to the medium of rat skin fibroblasts grown in culture caused nuclear abnormalities at concentrations as low as 10(-6) M despite an uptake of only 4%.
[1,3-14C] MDA was rapidly oxidized to [14C]acetate in rat liver mitochondria and to 14CO2 in vivo; however, approximately 10% of the radioactivity was recovered in the urine.
Chromatographic analysis of rat urine revealed the presence of several compounds which yield MDA on acid hydrolysis.
Total MDA excretion increased in response to conditions which stimulate lipid peroxidation in vivo, including vitamin E deficiency, Fe or CCl4 administration, and enrichment of the tissues with PUFA.
N-acetyl-e-(2-propenal)lysine was identified as a major urinary metabolite of MDA in rat and human urine. This compound is derived primarily from N-alpha-(2-propenal)lysine released in digestion as a product of reactions between MDA and the epsilon-amino groups of N-terminal lysine residues in food proteins. However, its presence in the urine of animals fasted or fed MDA-free diets indicates that it is also formed in vivo.(ABSTRACT TRUNCATED AT 250 WORDS).
Suomennos 22.1. 2018
Kommentti: Käytännössä tämä merkannee sitä,että PUFA- käytöllä on jokin suositeltu ylärajansa joka ehkä on individuelli.
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