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What are Lipids?01:38

What are Lipids?

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What are Lipids?01:31

What are Lipids?

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Lipids function as structural components of cellular membranes, in addition to acting as energy reservoirs and signaling molecules. They are thus crucial to all living organisms.  The three biologically important classes of lipids are triglycerides, phospholipids, and steroids.
Non-Polar and Hydrophobic Characteristics of Lipids
Lipids are a structurally and functionally diverse group of hydrocarbons—compounds consisting of carbon and hydrogen atoms. The carbon-carbon and...
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Lipid Digestion01:06

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Lipids are large molecules that are generally not water-soluble. Since most of the digestive enzymes in the human body are water-based, there are specific steps the body must take to break down lipids and make them available for use.
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Lipids include a diverse group of compounds that are largely nonpolar in nature. This is because they are hydrocarbons that include mostly nonpolar carbon-carbon or carbon-hydrogen bonds. Non-polar molecules are hydrophobic (“water fearing”), or insoluble in water. Lipids perform many different functions in a cell. Cells store energy for long-term use in the form of fats. Lipids also provide insulation from the environment for plants and animals. For example, they help keep aquatic...
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In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
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Lipid Catabolism

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Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...
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Schweinfurthins: Lipid Modulators with Promising Anticancer Activity.

Emily J Koubek1, Jillian S Weissenrieder2, Jeffrey D Neighbors3

  • 1Departments of Medicine and Pharmacology, The Pennsylvania State Cancer Institute, The Pennsylvania State College of Medicine, 500 University Drive Hershey, Hershey, PA 17033, USA.

Lipids
|October 19, 2018
PubMed
Summary

Schweinfurthins show potent anti-cancer activity by disrupting cancer cell lipid metabolism. Further research into their mechanism and sensitivity could lead to novel cancer therapeutics.

Keywords:
CholesterolOxysterol-binding proteinsPI3KPrenylationSphingomyelinStatinsSterols

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Area of Science:

  • Natural Product Chemistry
  • Cancer Biology
  • Medicinal Chemistry

Background:

  • The schweinfurthin family of compounds exhibits potent and differential cytotoxicity against human cancer cell lines.
  • Initial isolation of vedelianin in 1992 and other schweinfurthins in 1998 paved the way for analog synthesis and further research.
  • Current research explores the effects of schweinfurthins on tumor development and progression in animal models, showing promising results.

Purpose of the Study:

  • To review the history, synthesis, current research status, and outstanding questions regarding the schweinfurthin family of compounds.
  • To delineate the mechanism of action and identify factors influencing sensitivity to schweinfurthins.
  • To highlight the potential of schweinfurthins as novel cancer therapeutics by targeting cancer cell lipid metabolism.

Main Methods:

  • Literature review of historical data, synthesis methods, and mechanistic studies on schweinfurthins.
  • Analysis of research findings on the effects of schweinfurthins on lipid metabolism, including Golgi trafficking, lipid rafts, oxysterol-binding protein activity, and the isoprenoid biosynthesis pathway (IBP).
  • Examination of studies investigating the efficacy of schweinfurthins in preclinical cancer models.

Main Results:

  • Schweinfurthins demonstrate significant cytotoxicity against various cancer cell lines.
  • Intracellular effects of schweinfurthins are strongly linked to their impact on lipid metabolism, synthesis, and homeostasis.
  • Observed effects include impaired trans-Golgi network trafficking, disrupted lipid rafts, altered oxysterol-binding protein activity, and interference with the isoprenoid biosynthesis pathway (IBP).

Conclusions:

  • Schweinfurthins hold promise as novel therapeutic agents due to their ability to target critical lipid synthesis pathways essential for cancer cell growth and proliferation.
  • Understanding the precise mechanism of action and the basis of sensitivity is crucial for optimizing schweinfurthin-based cancer therapies.
  • Further investigation into schweinfurthins is warranted to fully exploit their therapeutic potential in oncology.