Cellular lipids

In 1914 A. Niemann described a type of storage disease which, however, he did not recognize. In 1926 L. Pick differentiated this clinical picture from Gaucher s disease and called it lipid cellular splenomegaly . The substance predominantly stored was identified as sphingomyelin by E. Klenk in 1934. Thus, this condition is a kind of phosphoryl ceramidosis. 

In addition to SREBPs, several members of the nuclear receptor superfamily regulate lipid metabolism. Nuclear receptors are transcription factors that are generally activated when bound to specific small-molecule ligands (Chapter 11). Certain nuclear receptors influence whole-body lipid metabolism by regulating the absorption of dietary lipids, cellular synthesis of lipids, transport protein-mediated import and export of lipids, levels of lipoproteins and their receptors, and catabolism of lipids (e.g., fatty acid oxidation in the peroxisome) and their secretion from the body. 

Additionally, energy deficits lead to ionic imbalance, and excito-toxic glutamate efflux and buUd up of intracellular calcium. Downstream pathways ultimately include direct free radical damage to membrane lipids, cellular proteins, and DNA, as well as calcium-activated proteases, plus caspase cascades that dismantle a wide range of homeostatic, reparative, and cytoskeletal proteins (courtesy of DaLkara et al. 2003)... 

Jones, P.J.H. and Papamandjaris, A.A. Lipids cellular metabolism. In Bowman, B.A. and Russell, R., Eds. Present Knowledge in Nutrition, 8th ed. ILSI Press, Washington, DC, 2001. 

Puller R C (1995) Polyesters and photosynthetic bacteria from lipid cellular inclusions to microbial thermoplastics, in Anoxygenic Photosynthetic Bacteria (Eds. Blankenship R E, Madigan M T and Bauer C E) Kluwer Academic Publishers, The Netherlands, Ch. 60, pp. 1245-1256. 

Biological membranes provide the essential barrier between cells and the organelles of which cells are composed. Cellular membranes are complicated extensive biomolecular sheetlike structures, mostly fonned by lipid molecules held together by cooperative nonco-valent interactions. A membrane is not a static structure, but rather a complex dynamical two-dimensional liquid crystalline fluid mosaic of oriented proteins and lipids. A number of experimental approaches can be used to investigate and characterize biological membranes. However, the complexity of membranes is such that experimental data remain very difficult to interpret at the microscopic level. In recent years, computational studies of membranes based on detailed atomic models, as summarized in Chapter 21, have greatly increased the ability to interpret experimental data, yielding a much-improved picture of the structure and dynamics of lipid bilayers and the relationship of those properties to membrane function [21]. 

There is a second family of small lipid-binding proteins, the P2 family, which include among others cellular retinol- and fatty acid-binding proteins as well as a protein, P2, from myelin in the peripheral nervous system. However, members of this second family have ten antiparallel p strands in their barrels compared with the eight strands found in the barrels of the RBP superfamily. Members of the P2 family show no amino acid sequence homology to members of the RBP superfamily. Nevertheless, their three-dimensional structures have similar architecture and topology, being up-and-down P barrels. 

Cell membrane The cell membrane is composed of about 45% lipid and 55% protein. The lipids form a bilayer that is a continuous nonpolar hydrophobic phase in which the proteins are embedded. The cell membrane is a highly selective permeability barrier that controls the entry of most substances into the cell. Important enzymes in the generation of cellular energy are located in the membrane. 

A rather limited collection of simple precursor molecules is sufficient to provide for the biosynthesis of virtually any cellular constituent, be it protein, nucleic acid, lipid, or polysaccharide. All of these substances are constructed from appropriate building blocks via the pathways of anabolism. In turn, the building blocks (amino acids, nucleotides, sugars, and fatty acids) can be generated from metabolites in the cell. For example, amino acids can be formed by amination of the corresponding a-keto acid carbon skeletons, and pyruvate can be converted to hexoses for polysaccharide biosynthesis. 

The insulin receptor is a transmembrane receptor tyrosine kinase located in the plasma membrane of insulin-sensitive cells (e.g., adipocytes, myocytes, hepatocytes). It mediates the effect of insulin on specific cellular responses (e.g., glucose transport, glycogen synthesis, lipid synthesis, protein synthesis). 

PKC is a family of enzymes whose members play central roles in transducing information from external stimuli to cellular responses. Members of this family of serine/ threonine kinases respond to signals that cause lipid hydrolysis. PKC isozymes phosphorylate an abundance of substrates, leading to both short-term cellular responses such as regulation of membrane transport and long-term responses such as memory and learning. 

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