Call us toll-free

Quick academic help

Don't let the stress of school get you down! Have your essay written by a professional writer before the deadline arrives.

Calculate the price

Pages:

275 Words

$19,50

Lipogenesis encompasses both de novo fatty acid synthesis and ..

Fatty acid synthase (FAS), the enzyme responsible for the de novo synthesis of fatty acids, is highly expressed in ovarian cancers and most common human carcinomas. Inhibition of FAS and activation of AMP-activated protein kinase (AMPK) have been shown to be cytotoxic to human cancer cells in vitro and in vivo. In this report, we explore the cytotoxic mechanism of action of FAS inhibition and show that C93, a synthetic FAS inhibitor, increases the AMP/ATP ratio, activating AMPK in SKOV3 human ovarian cancer cells, which leads to cytotoxicity. As a physiologic consequence of AMPK activation, acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis, was phosphorylated and inhibited whereas glucose oxidation was increased. Despite these attempts to conserve energy, the AMP/ATP ratio increased with worsening cellular redox status. Pretreatment of SKOV3 cells with compound C, an AMPK inhibitor, substantially rescued the cells from C93 cytotoxicity, indicating its dependence on AMPK activation. 5-(Tetradecyloxy)-2-furoic acid, an ACC inhibitor, did not activate AMPK despite inhibiting fatty acid synthesis pathway activity and was not significantly cytotoxic to SKOV3 cells. This indicates that substrate accumulation from FAS inhibition triggering AMPK activation, not end-product depletion of fatty acids, is likely responsible for AMPK activation. C93 also exhibited significant antitumor activity and apoptosis against SKOV3 xenografts in athymic mice without significant weight loss or cytotoxicity to proliferating cellular compartments such as bone marrow, gastrointestinal tract, or skin. Thus, pharmacologic FAS inhibition selectively activates AMPK in ovarian cancer cells, inducing cytotoxicity while sparing most normal human tissues from the pleiotropic effects of AMPK activation.

The rate of de novo fatty acid synthesis in developing rat lung was measured ..

of the antioxidant properties of tocopherols ().

First synthesis of linoleic acid ()

Kurz H used ethyl alcohol to derivatize fatty acids (FA ethyl esters) beforetheir analysis ().

First data on cholesterol and fatty acid metabolism after using an isotope of hydrogen(deuterium) in mice and chicks ().

Using deuterated acetate, Sonderhoff R et al. have shown that it serves asa precursor for sterols including ergosterol in yeast ().

Paul Karrer received the

De novo fatty Acid Synthesis- Introduction Fatty acids are ..

The end-product of these reactions is always . No intermediatesare released until palmitate is formed. After release from the ACP,palmitate is esterified to , as this is done with all freefatty acids inside cells to prevent lysis of the cell membranes. Iffurther elongation has to happen, the palmitoyl CoA, or any other from a dietaryacid, then moves into the , where itcan be elongated up to a length of 20 to 24 carbons by essentiallythe same chain of reactions as happens in the cytosolic ACP.

AB - Fatty acid synthase (FAS), the enzyme responsible for the de novo synthesis of fatty acids, is highly expressed in ovarian cancers and most common human carcinomas. Inhibition of FAS and activation of AMP-activated protein kinase (AMPK) have been shown to be cytotoxic to human cancer cells in vitro and in vivo. In this report, we explore the cytotoxic mechanism of action of FAS inhibition and show that C93, a synthetic FAS inhibitor, increases the AMP/ATP ratio, activating AMPK in SKOV3 human ovarian cancer cells, which leads to cytotoxicity. As a physiologic consequence of AMPK activation, acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis, was phosphorylated and inhibited whereas glucose oxidation was increased. Despite these attempts to conserve energy, the AMP/ATP ratio increased with worsening cellular redox status. Pretreatment of SKOV3 cells with compound C, an AMPK inhibitor, substantially rescued the cells from C93 cytotoxicity, indicating its dependence on AMPK activation. 5-(Tetradecyloxy)-2-furoic acid, an ACC inhibitor, did not activate AMPK despite inhibiting fatty acid synthesis pathway activity and was not significantly cytotoxic to SKOV3 cells. This indicates that substrate accumulation from FAS inhibition triggering AMPK activation, not end-product depletion of fatty acids, is likely responsible for AMPK activation. C93 also exhibited significant antitumor activity and apoptosis against SKOV3 xenografts in athymic mice without significant weight loss or cytotoxicity to proliferating cellular compartments such as bone marrow, gastrointestinal tract, or skin. Thus, pharmacologic FAS inhibition selectively activates AMPK in ovarian cancer cells, inducing cytotoxicity while sparing most normal human tissues from the pleiotropic effects of AMPK activation.

fatty acids depress de novo fatty acid synthesis

Among activators, a variety of endogenously present lipids were described ().

An antiphosphatidylcholine antibody was described in the serum of a patient diagnosed with hemolytic anemia ().

Phosphatidylserine was shown to be recognized by specific antibodies in patients with lupus anticoagulant ().

The "Nod factors" produced in legumes by as a class of signalling molecules was identified as lipo-chitooligosaccharides ().

First demonstration of phosphatidylinositol anchor on the lipopolysaccharides of a prokaryotic species, ( ).

Demonstration of the induction of the synthesis of proteinase inhibitors by methyl jasmonate in a wounded plant but also in nearby plants through the atmosphere ().

First clear demonstration that fatty acids are as unfavorable as saturated fatty acids in raising LDL cholesterol and lowering HDL cholesterol levels ().

N2 - Fatty acid synthase (FAS), the enzyme responsible for the de novo synthesis of fatty acids, is highly expressed in ovarian cancers and most common human carcinomas. Inhibition of FAS and activation of AMP-activated protein kinase (AMPK) have been shown to be cytotoxic to human cancer cells in vitro and in vivo. In this report, we explore the cytotoxic mechanism of action of FAS inhibition and show that C93, a synthetic FAS inhibitor, increases the AMP/ATP ratio, activating AMPK in SKOV3 human ovarian cancer cells, which leads to cytotoxicity. As a physiologic consequence of AMPK activation, acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis, was phosphorylated and inhibited whereas glucose oxidation was increased. Despite these attempts to conserve energy, the AMP/ATP ratio increased with worsening cellular redox status. Pretreatment of SKOV3 cells with compound C, an AMPK inhibitor, substantially rescued the cells from C93 cytotoxicity, indicating its dependence on AMPK activation. 5-(Tetradecyloxy)-2-furoic acid, an ACC inhibitor, did not activate AMPK despite inhibiting fatty acid synthesis pathway activity and was not significantly cytotoxic to SKOV3 cells. This indicates that substrate accumulation from FAS inhibition triggering AMPK activation, not end-product depletion of fatty acids, is likely responsible for AMPK activation. C93 also exhibited significant antitumor activity and apoptosis against SKOV3 xenografts in athymic mice without significant weight loss or cytotoxicity to proliferating cellular compartments such as bone marrow, gastrointestinal tract, or skin. Thus, pharmacologic FAS inhibition selectively activates AMPK in ovarian cancer cells, inducing cytotoxicity while sparing most normal human tissues from the pleiotropic effects of AMPK activation.

Order now
  • UNMATCHED QUALITY

    As soon as we have completed your work, it will be proofread and given a thorough scan for plagiarism.

  • STRICT PRIVACY

    Our clients' personal information is kept confidential, so rest assured that no one will find out about our cooperation.

  • COMPLETE ORIGINALITY

    We write everything from scratch. You'll be sure to receive a plagiarism-free paper every time you place an order.

  • ON-TIME DELIVERY

    We will complete your paper on time, giving you total peace of mind with every assignment you entrust us with.

  • FREE CORRECTIONS

    Want something changed in your paper? Request as many revisions as you want until you're completely satisfied with the outcome.

  • 24/7 SUPPORT

    We're always here to help you solve any possible issue. Feel free to give us a call or write a message in chat.

Order now
  • You submit your order instructions

  • We assign an appropriate expert

  • The expert takes care of your task

  • We send it to you upon completion

Order now
  • 37 684

    Delivered orders

  • 763

    Professional writers

  • 311

    Writers online

  • 4.8/5

    Average quality score

Order now
  • Kim

    "I have always been impressed by the quick turnaround and your thoroughness. Easily the most professional essay writing service on the web."

  • Paul

    "Your assistance and the first class service is much appreciated. My essay reads so well and without your help I'm sure I would have been marked down again on grammar and syntax."

  • Ellen

    "Thanks again for your excellent work with my assignments. No doubts you're true experts at what you do and very approachable."

  • Joyce

    "Very professional, cheap and friendly service. Thanks for writing two important essays for me, I wouldn't have written it myself because of the tight deadline."

  • Albert

    "Thanks for your cautious eye, attention to detail and overall superb service. Thanks to you, now I am confident that I can submit my term paper on time."

  • Mary

    "Thank you for the GREAT work you have done. Just wanted to tell that I'm very happy with my essay and will get back with more assignments soon."

Ready to tackle your homework?

Place an order