Enzymatic preparation of VLC-PUFA-enriched glycerolipids for potential pharmaceutical applications

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F24%3A43928986" target="_blank" >RIV/60461373:22330/24:43928986 - isvavai.cz</a>

Výsledek na webu

—

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

Enzymatic preparation of VLC-PUFA-enriched glycerolipids for potential pharmaceutical applications

Popis výsledku v původním jazyce

Very-long-chain polyunsaturated fatty acids (VLC-PUFAs) with chain lengths greater than C26 carbon atoms, usually, with 4 to 6 cis double bonds are found in the brain, retina, testes and spermatozoa. In these tissues, VLC-PUFAs are synthesized by the Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) enzyme from long chain polyunsaturated fatty acids (LC-PUFAs) precursors of the n-3 and n-6 series in a four-step cyclic reaction in which, the ELOVL4 mediates the first and rate-limiting condensation step. Once synthesized, VLC-PUFAs are differentially incorporated into glycerophospholipids or sphingolipids. In the brain and retina, they serve as precursors for the biosynthesis of neuroprotective signalling molecules – “Elovanoids”. Mutations in the ELOVL4 cause a number of different tissue-specific disorders, including blindness in Autosomal Dominant Stargardt Macular Dystrophy (STGD3), age-related cerebellar degeneration in Spinocerebellar ataxia-34 (SCA34) or early-childhood seizures in humans. Depletion/loss of VLC-PUFAs in testes and spermatozoa also affects fertility. However, currently, there are no large-scale sources of VLC-PUFAs that can be evaluated as therapeutic agents for treating the different mutant ELOVL4-induced human disorders. The main goal of this study was to develop chemical interesterification of triacylglycerols and glycerophospholipids with selected ethyl esters of VLC-PUFAs to enable us determine their uptake, and incorporation into ELOVL4 expressing tissues in vivo. We successfully developed methods for incorporation of analytical standards of VLC-PUFAs (C26:5 n-3 and C28:6 n-3) derivatives into triacylglycerols with medium chain fatty acyl moieties and into phosphatidylcholine. Structural analysis confirmed the formation of triacylglycerols containing VLC-PUFAs at the sn-1 and sn-3 positions as well as VLC-PUFA-rich phosphatidylcholine. Future studies will evaluate uptake and incorporation of these lipids into ELOVL4 expressing tissues in vivo.

Název v anglickém jazyce

Enzymatic preparation of VLC-PUFA-enriched glycerolipids for potential pharmaceutical applications

Popis výsledku anglicky

Very-long-chain polyunsaturated fatty acids (VLC-PUFAs) with chain lengths greater than C26 carbon atoms, usually, with 4 to 6 cis double bonds are found in the brain, retina, testes and spermatozoa. In these tissues, VLC-PUFAs are synthesized by the Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) enzyme from long chain polyunsaturated fatty acids (LC-PUFAs) precursors of the n-3 and n-6 series in a four-step cyclic reaction in which, the ELOVL4 mediates the first and rate-limiting condensation step. Once synthesized, VLC-PUFAs are differentially incorporated into glycerophospholipids or sphingolipids. In the brain and retina, they serve as precursors for the biosynthesis of neuroprotective signalling molecules – “Elovanoids”. Mutations in the ELOVL4 cause a number of different tissue-specific disorders, including blindness in Autosomal Dominant Stargardt Macular Dystrophy (STGD3), age-related cerebellar degeneration in Spinocerebellar ataxia-34 (SCA34) or early-childhood seizures in humans. Depletion/loss of VLC-PUFAs in testes and spermatozoa also affects fertility. However, currently, there are no large-scale sources of VLC-PUFAs that can be evaluated as therapeutic agents for treating the different mutant ELOVL4-induced human disorders. The main goal of this study was to develop chemical interesterification of triacylglycerols and glycerophospholipids with selected ethyl esters of VLC-PUFAs to enable us determine their uptake, and incorporation into ELOVL4 expressing tissues in vivo. We successfully developed methods for incorporation of analytical standards of VLC-PUFAs (C26:5 n-3 and C28:6 n-3) derivatives into triacylglycerols with medium chain fatty acyl moieties and into phosphatidylcholine. Structural analysis confirmed the formation of triacylglycerols containing VLC-PUFAs at the sn-1 and sn-3 positions as well as VLC-PUFA-rich phosphatidylcholine. Future studies will evaluate uptake and incorporation of these lipids into ELOVL4 expressing tissues in vivo.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

21101 - Food and beverages

Projekt

<a href="/cs/project/QK22010135" target="_blank" >QK22010135: Nové trvale udržitelné způsoby zpracování a využití tuzemských olejnin</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů