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Regulation of Cholesterol and Fatty Acid Synthesis

As an indicator of apoptosis, we examined caspase3/7 activity after Ad-TERE1 transduction and found increases in RCCcell lines: Caki-1 (by 40%), 786-O (by 60%), and ACHN (by 20%).This is consistent with reports of growth inhibition, autoschizis,necrosis, or a delayed apoptosis in different tumor cell lines inresponse to vitamin K-2 and K-3 (,–).Recently K-2 was found to form covalent adducts with the Bcl-2homologous antagonist killer protein, BAK, and induce BAK-mediatedapoptosis (). This facilitationof BAK activity by K-2 adduction is in contrast to thiol arylationadducts of K-3 that inactivate phosphatases. K-2 adduction suggestsa possible mechanism for the TERE1-mediated apoptosis we observedin RCC cell lines, and raises the possibility of K-2 adductformation with other targets, especially, TERE1-interactingproteins. Overall, TERE1-mediated K-2 synthesis has multiplepossible mechanisms capable of affecting cell growth, which mayaccount for some of the differences observed between the celllines. Although ectopic expression likely exaggeratesTERE1-mediated effects, the apparent liability TERE1 poses to RCCcell growth, may account for its low level or absence in over halfof the RCC tumor specimens and cell lines.É

Fatty Acid Synthesis - Duration: ..

Kidney cancer is the third most common genitourinarycancer with 64,770 new cases per year in the US in 2012 (,). Themajority (75%) are renal clear cell carcinomas (RCC), which havethe highest mortality to incidence ratios or all urologicmalignancies resulting in 13,570 deaths per year due to theirextreme insensitivity to chemo- and radiation therapy. Theincidence is twice as high in men than women and associated withrisk factors such as: advanced age, tobacco use, and obesity(,). In the majority of RCC, the HIF1complex is constitutively activated due to mutation of the VonHippel-Lindau tumor suppressor (VHL), gene and inactivation of theprolyl hydro-xylation that targets the HIFs to be degraded(,). As a result of HIF1 stabilization,there is an induction of a hypoxic gene expression program (GLUT1,VEGF, iNOS, EPO) that support proteins involved in angiogenesis andoxygenation (,,).This had led to therapies targeting angiogenesis which haveachieved only partial responses (,),and the necessity for further research into new factors involved inRCC progression. A role for elevated tumor cell cholesterol andaltered lipid metabolism has been implicated in the etiology anddisease progression in renal clear cell cancer based on itspotential for apoptotic interference (,–).Currently favored theories propose that RCC consists of a group ofdiseases of abnormal metabolism relating to oxygen, iron, energyand nutrient sensing pathways (,,).The concept of an aberrant metabolic phenotype of RCC has beenfurther supported by several studies elaborating mechanisms ofdefects in mitochondrial metabolism in the TCA cycle that lead tometabolic imbalance and HIF1 stabilization (–).Our current study of the role of TERE1 in RCC is based on its rolein synthesis of menaquinone ()that exerts profound influence on mitochondrial function, oxidativeand nitrosative stress, and regulation of lipid metabolism viaactivation of SXR nuclear receptor signaling, and several othermechanisms that lead to growth inhibition and increased apoptosis().

Glossary | Linus Pauling Institute | Oregon State University

What are some of the differences between fatty acid degradation and synthesis

We have discovered an enzymatic method of producing reduced calorie synthetic triglycerides using lipases from or as catalysts. These lipases are highly fatty acid specific and the reaction is carried out at moderate temperatures. The triglycerides can be made by this novel method when they have medium- and/or short-chain fatty acids at the 2 and at one of the primary positions and an unsaturated fatty acid having a chain length of at least 18 carbons at the remaining primary position.

Human Physiology - Cell structure and function

Fatty Acid Synthesis

The lipid synthesis and metabolism page provides a detailed description of the structure, synthesis and metabolism of fatty acids, triglycerides, and phospholipids.
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