Transfer of lipid across the cytoplasm is an essential process for intracellular lipid traffic. Lipid transfer proteins (LTPs) are defined by highly controlled in vitro experiments. The functional relevance of these is supported by evidence for the same reactions inside cells. Major advances in the LTP field have come from structural bioinformatics identifying new LTPs, and from the development of countercurrent models for LTPs. However, the ultimate aim is to unite in vitro and in vivo data, and this is where much progress remains to be made. Even where in vitro and in vivo experiments align, rates of transfer tend not to match. Here we set out some of the advances that might test how LTPs work.
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http://dx.doi.org/10.1016/j.tibs.2017.05.001 | DOI Listing |
J Mater Chem B
January 2025
Department of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
Nanoparticles capable of dynamically reporting their structural integrity in real-time are a powerful tool to guide the design of drug delivery technologies. Lipid nanoparticles (LNPs) offer multiple important advantages for drug delivery, including stability, protection of active substances, and sustained release capabilities. However, tracking their structural integrity and dynamic behaviour in complex biological environments remains challenging.
View Article and Find Full Text PDFBiochem Pharmacol
January 2025
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan. Electronic address:
Lomitapide, a microsomal triglyceride transfer protein inhibitor, is a lipid-lowering drug that inhibits chylomicron formation in enterocytes and very low-density lipoprotein (VLDL) formation in the liver. Previous studies have shown that very low-density lipoprotein and/or low-density lipoprotein (VLDL/LDL) can deliver certain drugs in addition to lipids. Thus, we hypothesized that serum concentrations of drugs that are more likely to be distributed to VLDL/LDL in the serum (referred to as "VLDL/LDL-philic drugs" in this paper) may be altered by co-administered lomitapide.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Biol Lipids
January 2025
Department of Applied Chemistry for Environment, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen-Uegahara, Sanda, Hyogo 669-1330, Japan.
Carotenoids are naturally occurring pigments essential for both light-harvesting and photoprotection in photosynthetic processes. Among these, carbonyl-containing carotenoids exhibit distinctive excited state properties due to the presence of intramolecular charge transfer (ICT) in their excited states. In this study, we synthesized a novel family of carotenoid analogs with varying numbers of conjugated double bonds, denoted as the Ind series, and conducted femtosecond pump-probe spectroscopy on these molecules in both acetone and n-hexane.
View Article and Find Full Text PDFStructure
January 2025
Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address:
Glycosyltransferases (GTs) catalyze the addition of sugars to diverse substrates facilitating complex glycoconjugate biosynthesis across all domains of life. When embedded in or associated with the membrane, these enzymes often depend on polyisoprenyl-phosphate or -pyrophosphate (PP) lipid carriers, including undecaprenyl phosphate in bacteria and dolichol phosphate in eukaryotes, to transfer glycan moieties. GTs that bind PP substrates (PP-GTs) are functionally diverse but share some common structural features within their family or subfamily, particularly with respect to how they interact with their cognate PP ligands.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada.
The ionizable lipid component of lipid nanoparticle (LNP) formulations is essential for mRNA delivery by facilitating endosomal escape. Conventionally, these lipids are synthesized through complex, multistep chemical processes that are both time-consuming and require significant engineering. Furthermore, the development of new ionizable lipids is hindered by a limited understanding of the structure-activity relationships essential for effective mRNA delivery.
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