Lipids Play Other Cellular Roles

In addition to those cellular lipid functions introduced earlier, some classes of these lipids possess some other unique functions in cellular processes, which should be recognized and are very useful for data interpretation. In this section, some examples of these lipid classes and their cellular functions (Table 16.1) are overviewed. 

Acylcarnitines play an important role in fatty acyl transport in and out mitochondria. Two transport machineries are associated with this process, that is, carnitine palmitoyltransferase (CPT) I and II. In the context of inborn mitochondrial diseases, acylcarnitine production has been viewed as a detoxifying system that permits mitochondrial efflux of excess of acyl groups [54]. Unlike long-chain acylcarnitines, medium-chain species do not depend on the CPT system for transfer to the mitochondrial matrix [55]. 

LysoPC species constitute an important class of bioactive molecules, which showed to be implicated in inflammatory disorders [68-71]. Some unsaturated lysoPCs especially those containing 20 4 and 22 6 [72, 73] may have anti-inflammatory properties compared to the saturated ones such as 14 0 and 16 0 lysoPC. LysoGPL species represent an interesting class of biochemical intermediates, which are involved in both biosynthesis and metabolism of diradyl GPL species that constitute the cellular lipid bilayer of all animal cells [74]. 

Plasmalogen species play many roles in cellular functions in addition to serving as a biomembrane component. Previous studies demonstrated that membranes comprised of plasmalogen species possess a compact membrane conformation and unique membrane dynamics in comparison to membranes comprised of its diacyl counterpart [75-78]. A central role of plasmalogen PE in facilitating membrane fusion and cell-cell communication [79, 80] was demonstrated and the propensity for membrane fusion is directly linked with the quantity of the double bonds present in the GPL acyl chains of the membrane [81]. The role of plasmalogen as an antioxidant 

In addition to its role as a membrane structural lipid, PS has many unique cellular functions. PS serves as an important precursor of mitochondrial PE in mammalian cells (see Section 16.3.2) [24], PS exposure on the cell surface is an early event in apoptosis, which is believed to be one of the recognition signals by which apoptotic cells are removed by phagocytes [90, 91], PS also serves as a cofactor in activation of several key signaling proteins, including protein kinase C, neutral SMase, Na /K ATPase, and dynamin-1 (see review [23, 24] for original literature). 

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Outline of pathways for the biosynthesis of major cellular lipids (other than cholesterol) in a mammalian cell. Most of the metabolism of these lipids occurs on membrane surfaces because of the insoluble nature of the substrates and products. These lipids play three major roles (l) they act as a storehouse of chemical energy, as with triacylglycerols (2) they are structural components of membranes (boxed compounds) and (3) they act as regulatory compounds (underlined), either as eicosanoids, which act as local hormones, or as phosphorylated inositols and diacylglycerols, which function as second messengers. 

As discussed for N-myristoylation and S-prenylation, even S-acylation of proteins with a fatty acid which in the vast majority of cases is the C16 0 palmitic acid, plays a fundamental role in the cellular signal-transduction process (Table l). 2-5 14 While N-myristoylation and S-prenylation are permanent protein modifications due to the amide- and sulfide-type linkage, the thioester bond between palmitic acid and the peptide chain is rather labile and palmi-toylation is referred to as a dynamic modification. 64 This reversibility plays a crucial role in the modulation of protein functions since the presence or absence of a palmitoyl chain can determine the membrane localization of the protein and can also be used to regulate the interactions of these proteins with other proteins. Furthermore, a unique consensus sequence for protein palmitoylation has not been found, in contrast to the strict consensus sequences required for N-myristoylation and S-prenylation. Palmitoylation can occur at N- or C-terminal parts of the polypeptide chain depending on the protein family and often coexists with other types of lipidation (see Section 6.4.1.4). Given the diversity of protein sequences... 

Ptdins 3-kinases and the lipid messengers they produce play an important role in growth regulation and in several other cellular responses, including the insulin response (Chapter 8). The Class 1 Ptdins 3-kinases are regulated by Ras. Ras-GTP binds to the regulatory subunit of the kinase. Cells expressing Ras mutants that can not interact with Ptdins 3-kinases have lost certain responses. 

Despite the large number of protein kinases types, studies on natural activators focus mainly on PKC activation. This kinase, which plays a decisive role in many cellular responses, is generally activated in the cell by lipid second messengers, predominantly DAG, in response to various extracellular agonists (hormones, neurotransmitters, growth factors and cytokines). We now turn our attention to some of the best known PKC activators together with other novel compounds. 

Vitamin E is a fat soluble vitamin that appears to protect against oxidative damage in cellular membranes. Vitamin E is also called ot-tocopherol. Vitamin E is an antioxidant. It is particularly effective in preventing the attack of peroxides on unsatured fatty acids in membrane lipids. Deficiency of vitamin E also leads to other symptoms, however, so vitamin E probably plays other roles as yet undiscovered. 

Although neutral triacylglycerols (TAG), the most common form of storage lipid, are not considered a major structural element in food tissues, other lipids (e.g., phospholipids) are essential for the formation of cellular membranes. In addition, phospholipids play a decisive role in some food formulations by serving as emulsihers. 

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