Lipiidide ja lipoproteiinide biokeemia
TalTech prioriteetne teadussuund
Klassifikaator (Frascati)
Uurimisrühma juht
Uurimisrühma liige
Doktorant
Võtmesõna
lipiidide ja lipoproteiinide metabolismi regulatsioonimehhanismid
biomolekulaarsed interaktsioonid
lipaasid
lipiidide analüüs
Ülevaade
Uurimisrühma põhitemaatika on seotud lipiidide ja lipoproteiinide metabolismi fundamentaalsete aspektide väljaselgitamisega. Uurimise põhifookuses on lipaaside ja lipoksügenaaside regulatsiooni mehhanismid. Rühmal on kompetents ja kogemused valkude struktuuri ja omaduste uurimises, biomolekulaarsete interaktsioonide analüüsis, ensümoloogias ja lipidiide analüüsis. Uurimistöös kasutatakse massi spektromeetriat, kromatograafiat, kalorimeetriat, pinnaplasmonite resonantsi ning fluorestsentsil põhinevaid tehnoloogiaid.
Tähtsamad tulemused
2023. a olulisemad tulemused:Uurimisrühma viimase aasta tulemused on seotud triglütseriididerikaste lipoproteiinide metabolismi regulatsioonimehhanismide väljaselgitamisega. Oleme edasi arendanud kalorimeetrilist lipolüüsi uurimiseks füsioloogilstes tingimustes. Kombineerides seda meetodit erinevate biofüüsikaliste tehnikatega, nagu pinnaplasmonresonants, fluorestsentskorrelatsioonspektroskoopia ja mikroskoopia, uurisime lipoproteiini lipaasi oligomerisatsiooni füsioloogilistes tingimustes. Neid meetodeid kasutades pakuti välja mehhanism lipoproteiini lipaasi oligomerisatsiooni regulatsiooniks hepariini ja albumiini kombineeritud toimel füsiologilistes tingimusteks. Kasutades kalorimeetrilist meetodit, võrreldilipoproteiini lipaasi aktiivsust veganite ja kõigesööjate vereseerumis. Ei täheldatud olulist erinevust keskmises lipoproteiini lipaasi aktiivsuses, mõõdetuna kõigesööjate ja veganite seerumis. Selle uuringu tulemused viitavad ka sellele, et vegantoidu lipiididega seotud antiaterogeensus piirdub kolesterooli alandamisega.
Seotud projektid
Seotud struktuuriüksus
Teadusgrupiga seotud publikatsioonid
- Risti, R., Gunn, G. H., Hiis-Hommuk, K., Seeba, N., Villo, L., Vendelin, M., Neher, S. B., Lõokene, A. Albumin affects the stability, oligomerization and ligand interactions of lipoprotein lipase // Atherosclerosis (2022) vol. 355, p. 68.
https://doi.org/10.1016/j.atherosclerosis.2022.06.428 - Metz, M., Beghini, M., Wolf, P., Pfleger, L., Hackl, M., Bastian. M., Freudenthaler, A., Harreiter, J., Risti, R., Lõokene, A. et al. Leptin increases hepatic triglyceride export via a vagal mechanism in humans // Cell Metabolism (2022) vol. 34, 11, p. 1719-1731.
https://doi.org/10.1016/j.cmet.2022.09.020 - Rump, A., Risti, R., Kristal M.-L., Reut, J., Syritski, V., Lõokene, A., Rüütel Boudinot, S. Dual ELISA using SARS-CoV-2 N protein produced in E. coli and CHO cells reveals epitope masking by N-glycosylation // Biochemical and biophysical research communications (2021) vol. 534, p. 457−460.
https://doi.org/10.1016/j.bbrc.2020.11.060 - Villo, L., Risti, R., Reimund, M., Kukk, K., Samel, N., Lõokene, A. Calorimetric approach for comparison of Angiopoietin-like protein 4 with other pancreatic lipase inhibitors // Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (2020) vol. 1865, 2, art. 158553, 12 p. : ill.
https://doi.org/10.1016/j.bbalip.2019.158553 - Risti, R., Villo, L., Lõokene, A. Calorimetric assay reveals the importance of substrate choice for determination of lipoprotein lipase activity // Atherosclerosis (2021) Vol. 331, p. e122.
https://doi.org/10.1016/j.atherosclerosis.2021.06.361 - Wolska, A., Reimund, M., Remaley, A.T. Apolipoprotein C-II : the re-emergence of a forgotten factor // Current opinion in lipidology (2020) vol. 31, 3, p. 147-153.
https://doi.org/10.1097/MOL.0000000000000680 - Wolska, A., Reimund, M., Sviridov, D. O., Amar, M. J., Remaley, A. T. Apolipoprotein mimetic peptides : potential new therapies for cardiovascular diseases // Cells (2021) vol. 10, 3, art. 597.
https://doi.org/10.3390/cells10030597 - Kaasik, M., Martõnova, J., Erkman, K., Metsala, A., Järving, I., Kanger, T. Enantioselective Michael addition to vinyl phosphonates via hydrogen bond-enhanced halogen bond catalysis // Chemical science (2021) vol. 12, 21, p. 7561-7568.
https://doi.org/10.1039/D1SC01029H - Trubitsõn, D., Martõnova, J., Erkman, K., Metsala, A., Saame, J., Kõster, K., Järving, I., Leito, I., Kanger, T. Enantioselective N-Alkylation of Nitroindoles under Phase-Transfer Catalysis // Synthesis (2020) vol. 52, 7, p. 1047-1059.
https://doi.org/10.1055/s-0039-1690751 - Sorokin, A. V., Patel, N., Abdelrahman, K. M., Ling, C., Reimund, M., Graziano, G., Sampson, M., Playford, M. P. et al. Complex association of apolipoprotein E–containing HDL with coronary artery disease burden in cardiovascular disease // JCI Insight (2022) vol. 7, 10, art. e159577.
https://doi.org/10.1172/jci.insight.159577 - Lõhelaid, H., Anttila, J. E., Liew, H.-K., Tseng, K.-Y., Teppo, J., Stratoulias, V., Airavaara, M. UPR responsive genes Manf and Xbp1 in stroke // Frontiers in cellular neuroscience (2022) vol. 16, art. 900725.
https://doi.org/10.3389/fncel.2022.900725 - Ping, K., Alam, M., Kahnert, S. R., Bhadoria, R., Mere, A., Mikli, V., Käärik, M., Aruväli, J., Paiste, P., Kikas, A., Kisand, V., Järving, I., Leis, J., Kongi, N., Starkov, P. Multi-purpose heterogeneous catalyst material from an amorphous cobalt metal–organic framework // Materials advances (2021) vol. 2, p. 4009-4015.
https://doi.org/10.1039/D1MA00414J - Mõttus, J., Maiste, S., Eek, P., Truve, E., Sarmiento, C. Mutational analysis of Arabidopsis thaliana ABCE2 identifies important motifs for its RNA silencing suppressor function // Plant Biology (2021) vol. 23, Issue 1, p. 21-31 : ill.
https://doi.org/10.1111/plb.13193 - Kõllo, M., Kasari, M., Kasari, V., Pehk, T., Järving, I., Lopp, M., Jõers, A., Kanger, T. Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols // Beilstein journal of organic chemistry (2021) vol. 17, p. 581–588.
https://doi.org/10.3762/bjoc.17.52 - Kriis, K., Martõnov, H., Miller, A., Erkman, K., Järving, I., Kaasik, M., Kanger, T. Multifunctional catalysts in the asymmetric Mannich reaction of malononitrile with N-Phosphinoylimines : coactivation by halogen bonding versus hydrogen bonding // The journal of organic chemistry (2022) vol. 87, 11, p. 7422-7435 : ill.
https://doi.org/10.1021/acs.joc.2c00674 - Parve, J., Kudryašova, M., Shalima, T., Villo, L., Liblikas, I., Reile, I., Pehk, T., Gathergood, N., Aav, R., Vares, L., Parve, O. Scalable lipase-catalyzed synthesis of (R)-4-(Acyloxy)pentanoic acids from racemic γ-valerolactone // ACS sustainable chemistry & engineering (2021) vol. 9, 4, p. 1494−1499.
https://doi.org/10.1021/acssuschemeng.0c07918 - Tang, X., Teder, T., Samuelsson, B., Haeggström, J. Z. The IRE1α inhibitor KIRA6 blocks Leukotriene Biosynthesis in human phagocytes // Frontiers in pharmacology (2022) vol. 13, art. 806240.
https://doi.org/10.3389/fphar.2022.806240 - Murre, A., Erkman, K., Järving, I., Kanger, T. Asymmetric chemoenzymatic one-pot synthesis of α-Hydroxy half-esters // ACS Omega (2021) vol. 6, 31, p. 20686-20698 : ill.
https://doi.org/10.1021/acsomega.1c02973 - Lopušanskaja, E., Kooli, A., Paju, A., Järving, I., Lopp, M. Towards ortho-selective electrophilic substitution/addition to phenolates in anhydrous solvents // Tetrahedron (2021) vol. 83, 12, art. 131935, 9 p.
https://doi.org/10.1016/j.tet.2021.131935 - Kimm, M., Järving, I., Ošeka, M., Kanger, T. Asymmetric organocatalytic [2,3]-Wittig rearrangement of cyclohexanone derivatives // European journal of organic chemistry (2021) 21, p. 3113−3120 : ill.
https://doi.org/10.1002/ejoc.202100435 - Silm, E., Järving, I., Kanger, T. Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole // Beilstein Journal of Organic Chemistry (2022) vol. 18, p. 167-173.
https://doi.org/10.3762/bjoc.18.18 - Põldemaa, K., Lipp, M., Järving, I., Samel, N., Eek, P. Gly188Arg substitution eliminates substrate inhibition in arachidonate 11R-lipoxygenase // Biochemical and biophysical research communications (2019) vol. 519, 1, p. 81-85 : ill.
https://doi.org/10.1016/j.bbrc.2019.08.132 - Ernits, K., Eek, P., Lukk, T. et al. First crystal structure of an endo-levanase - the BT1760 from a human gut commensal Bacteroides thetaiotaomicron // Scientific reports (2019) vol. 9, 1, art. 8443, 13 p. : ill.
https://doi.org/10.1038/s41598-019-44785-0 - Teder, T., Samel, N., Lõhelaid, H Distinct characteristics of the substrate binding between highly homologous catalase-related allene oxide synthase and hydroperoxide lyase // Archives of biochemistry and biophysics (2019) vol. 676, art. 108126, 10 p. : ill.
https://doi.org/10.1016/j.abb.2019.108126 - Mihklepp, K., Kivirand, K., Juronen, D., Lõokene, A., Rinken, T. Immunodetection of Streptococcus uberis pathogen in raw milk // Enzyme and microbial technology (2019) vol. 130, art. 109360, 6 p. : ill.
https://doi.org/10.1016/j.enzmictec.2019.109360 - Lopušanskaja, E., Paju, A., Järving, I., Lopp, M. Synthesis of cyclic 3-aryl-substituted 1,2-dicarbonyl compounds via Suzuki cross-coupling reactions // Synthesis (2018) vol. 50, 9, p. 1883-1890 : ill.
https://doi.org/10.1055/s-0036-1591543 - Maljutenko, K., Borovkov, V., Kananovich, D., Järving, I., Lopp, M. Aerobic cascade oxidation of substituted cyclopentane-1,2-diones using metalloporphyrin catalysts // Tetrahedron (2018) vol. 74, 6, p. 661−664 : ill.
https://doi.org/10.1016/j.tet.2017.12.009 - Murre, A., Erkman, K., Kaabel, S., Järving, I., Kanger, T. Diastereoselective [2,3]-sigmatropic rearrangement of N-allyl ammonium ylides // Synthesis (2019) vol. 51, 22, p. 4183–4197.
https://doi.org/10.1055/s-0039-1690185 - Silm, E., Kaabel, S., Järving, I., Kanger, T. Asymmetric organocatalytic Michael addition–cyclisation cascade of cyclopentane-1,2-dione with alkylidene malononitriles // Synthesis (2019) vol. 51, 22, p. 4198-4204.
https://doi.org/10.1055/s-0039-1690484 - Reitel, K., Kriis, K., Järvin, I., Kanger, T. Study of the asymmetric organocatalyzed [3+2] annulation of cyclopropenone and β-keto ester // Chemistry of heterocyclic compounds (2018) vol. 54, 10, p. 929–933 : ill.
https://doi.org/10.1007/s10593-018-2372-1 - Ping, K., Alam, M., Käärik, M., Leis, J., Kongi, N., Järving, I., Starkov, P. Surveying iron–organic framework TAL-1-derived materials in ligandless heterogeneous oxidative catalytic transformations of alkylarenes // Synlett (2019) vol. 30, p. 1536–1540 : ill.
https://doi.org/10.1055/s-0037-1611877 - Prigorchenko, E. Kaabel, S., Narva, T., Baškir, A., Fomitšenko, M., Adamson, J., Järving, I., Rissanen, K., Tamm, T., Aav, R. Formation and trapping of the thermodynamically unfavoured inverted-hemicucurbit[6]uril // Chemical communications (2019) vol. 55, 63, p. 9307−9310 : ill.
https://doi.org/10.1039/C9CC04990H - Kasak, L., Näks, M., Eek, P., Bhadoria, R., Starkov, P., Piirsoo, M. et al. Characterization of protein kinase ULK3 regulation by phosphorylation and inhibition by small molecule SU6668 // Biochemistry (2018) vol. 57, 37, p. 5456−5465.
https://doi.org/10.1021/acs.biochem.8b00356 - Trubitsõn, D., Žari, S., Kaabel, S., Kudrjashova, M., Kriis, K., Järving, I., Pehk, T., Kanger, T. Asymmetric organocatalytic cascade synthesis of tetrahydrofuranyl spirooxindoles // Synthesis (2018) vol. 50, 2, p. 314-322 : ill.
https://doi.org/10.1055/s-0036-1590918 - Kimm, M., Ošeka, M., Kaabel, S., Metsala, A., Järving, I., Kanger, T. [2,3]-Wittig rearrangement as a formal asymmetric alkylation of α-branched ketones // Organic letters (2019) vol. 21, 13, p. 4976-4980.
https://doi.org/10.1021/acs.orglett.9b01495 - Lõhelaid, H., Samel, N. Eicosanoid diversity of stony corals // Marine drugs (2018) vol. 16, 1, p. 1-14 : ill.
https://doi.org/10.3390/md16010010 - Ballarin, L., Rinkevich, B., Bartscherer, K., Burzynski, A., Cambier, S., Cammarata, M., Domart-Coulon, I., Drobne, D., Encinas, J., Frank, U., Geneviere, A.-M., Hobmayer, B., Löhelaid, H., Lyons, D., Martinez, P., Oliveri, P., Peric, L., Piraino, S., Ramšak, A., Rakers, S., Rentzsch, F., Rosner, A., Silva, T.H. da, Somorjai, I., Suleiman, S., Coelho, A.V. Maristem - stem cells of marine/aquatic invertebrates : from basic research to innovative applications // Sustainability (Switzerland) (2018) Vol. 10, Issue 2, Art. 526.
https://doi.org/10.3390/su10020526 - Ermolovich, Y., Barysevich, M., Adamson, J., Rogova, O., Kaabel, S., Järving, I.,Gathergood, N., Kananovich, D. G. Site-selective and stereoselective C–H functionalization of N-Cyclopropylamides via a directed remote metalation strategy // Organic letters (2019) vol. 21, 4, p. 969-973 : ill.
https://doi.org/10.1021/acs.orglett.8b03955 - Elek, G.Z., Koppel, K., Zubrytski, D., Konrad, N., Järving, I., Lopp, M., Kananovich, D. Divergent access to histone deacetylase inhibitory cyclopeptides via a late-stage cyclopropane ring Cleavage strategy. Short synthesis of Chlamydocin // Organic letters (2019) vol. 21, 20, p. 8473-8478 : ill.
https://doi.org/10.1021/acs.orglett.9b03305 - Reimund, M., Wolska, A., Risti, R., Wilson, S., Sviridov, D., Remaley, A.T., Lõokene, A. Apolipoprotein C-II mimetic peptide is an efficient activator of lipoprotein lipase in human plasma as studied by a calorimetric approach // Biochemical and biophysical research communications (2019) vol. 519, 1, p. 67-72.
https://doi.org/10.1016/j.bbrc.2019.08.130 - Peterson, A., Kaasik, M., Metsala, A., Järving, I., Adamson, J., Kanger, T. Tunable chiral triazole-based halogen bond donors : assessment of donor strength in solution with nitrogen-containing acceptors // RSC advances (2019) vol. 9, 21, p. 11718–11721 : ill.
https://doi.org/10.1039/c9ra01692a - Kaasik, M., Kaabel, S., Kriis, K., Järving, I., Kanger, T. Synthesis of chiral triazole-based halogen bond donors // Synthesis (2019) vol. 51, 10, p. 2128-2135 : ill.
https://doi.org/10.1055/s-0037-1610864 - Kaabel, S., Stein, R. S., Fomitšenko, M., Järving, I., Frišcic, T, Aav, R. Size-control by anion templating in mechanochemical synthesis of hemicucurbiturils in the solid state // Angewandte Chemie international edition (2019) vol. 58, 19, p. 6230-6234 : ill.
https://doi.org/10.1002/anie.201813431 - Smirnova, J., Kabin, E., Järving, I., Bragina, O., Tõugu, V., Plitz, T., Palumaa, P. Copper(I)-binding properties of de-coppering drugs for the treatment of Wilson disease. α-Lipoic acid as a potential anti-copper agent // Scientific reports (2018) 8, 1, art. 1463, 9 p. : ill.
https://doi.org/10.1038/s41598-018-19873-2 - Kaasik, M., Metsala, A., Kaabel, S., Kriis, K., Järving, I., Kanger, T. Halo-1,2,3-triazolium salts as halogen bond donors for the activation of imines in dihydropyridinone synthesis // Journal of organic chemistry (2019) vol. 84, 7, p. 4294–4303 : ill.
https://doi.org/10.1021/acs.joc.9b00248 - Donovan, B. T., Chen, H., Eek, P., Meng, Z., Jipa, C., Tan, S., Bai, L., Poirier, M. G. Basic helix-loop-helix pioneer factors interact with the histone octamer to invade nucleosomes and generate nucleosome-depleted regions // Molecular cell (2023) vol. 83, 8, p. 1251-1263.e6.
https://doi.org/10.1016/j.molcel.2023.03.006 - Kobzar, G. Inhibition of platelet activation using vitamins // Platelets (2020) vol. 31, 2, p. 157-166.
https://doi.org/10.1080/09537104.2019.1652262 - Risti, R., Gunn, K. H., Hiis-Hommuk, K., SeebaN-N., Karimi, H., Villo, L., Vendelin, M., Neher, S. B., Lõokene, A. Combined action of albumin and heparin regulates lipoprotein lipase oligomerization, stability, and ligand interactions // PLoS ONE (2023) vol. 18, 4, art. e0283358, 24 p. : ill.
https://doi.org/10.1371/journal.pone.0283358 - Teder, T., Haeggström, J.Z., Airavaara, M., Lõhelaid, H. Cross-talk between bioactive lipid mediators and the unfolded protein response in ischemic stroke // Prostaglandins & other lipid mediators (2023) vol. 168, art. 106760.
https://doi.org/10.1016/j.prostaglandins.2023.106760 - Bhadoria, R., Ping, K., Lohk, C., Järving, I., Starkov, P. A phenotypic approach to probing cellular outcomes using heterobivalent constructs // Chemical Communications (2020) Vol. 56,30, p. 4216 - 4219.
https://doi.org/10.1039/c9cc09595k https://pubs.rsc.org/en/content/articlelanding/2020/cc/c9cc09595k - Teder, T., König, S., Singh, R., Samuelsson, B., Werz, O., Garscha, U.,
Haeggström, J. Z. Modulation of the 5-lipoxygenase pathway by chalcogen-containing inhibitors of leukotriene A4 hydrolase // International journal of molecular sciences (2023) vol. 24, 8, art. 7539.
https://doi.org/10.3390/ijms24087539 - Ernits, K, Eek, P., Lukk, T., Visnapuu, T., Alamäe, T. Author correction: First crystal structure of an endo-levanase – the BT1760 from a human gut commensal Bacteroides thetaiotaomicron (Scientific Reports, (2019), 9, 1, (8443), 10.1038/s41598-019-44785-0) // Scientific reports (2019) vol. 9, 1, art. 17512, 1 p..
https://doi.org/10.1038/s41598-019-54274-z - Seeba, N-N. S., Risti, R., Lõokene, A. Lipoprotein lipase activity does not differ in the serum environment of vegans and omnivores // Nutrients (2023) vol. 15, 12, art. 2755.
https://doi.org/10.3390/nu15122755 - Bondar, D., Bragina, O., Lee, J., Semenyuta, I., Järving, I., Brovarets, V., Wipf, P., Bahar, I., Karpichev, Y. Hydroxamic acids as PARP-1 inhibitors : molecular design and anticancer activity of novel phenanthridinones // Helvetica chimica acta (2023) vol. 196, 10, art. e202300133, 26 p. : ill.
https://doi.org/10.1002/hlca.202300133 - Parve, J., Kudryashova, M., Shalima, T., Villo, L., Ferschel, M., Niidu, A., Liblikas, I., Reile, I., Aav, R., Gathergood, N., Vares, L., Pehk, T., Parve, O. Stereoselective Synthesis of γ-(Acyloxy)Carboxylic Acids and γ-Lactones Features the Switch of Stereopreference of CalB Along Sodium γ-Hydroxycarboxylate Homologues // European journal of organic chemistry (2023) vol. 26, 3, art. e202201329.
https://doi.org/10.1002/ejoc.202201329