3 Биологические мембраны. Обмен веществом (1160072), страница 5
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Bilayerformation occurs most readily when the cross-sectional areas of thehead group and side chain(s) are similar (Fig. 9-14b), as inglycerophospholipids and sphingolipids. The hydrophobic portions ineach monolayer interact, excluding water. The hydrophilic headgroups interact with water at the two surfaces of the bilayer.The third type of lipid aggregate is formed when a lipid bilayerfolds back on itself to form a hollow sphere called a liposome or vesicle(Fig. 9-14c). By forming vesicles, bilayer sheets lose their hydrophobicedge regions, achieving maximal stability in their aqueous environment.
These bilayer vesicles enclose water, creating a separate aqueous compartment. It is likely that the first living cells resembled liposomes, their aqueous contents segregated from the rest of the world bya hydrophobic shell. We shall see in the next chapter that lipid bilayersare fundamental to the structure of all biological membranes.Lipids with Specific Biological ActivitiesThe two classes of lipids considered thus far (storage lipids and structural lipids) are major cellular components; membrane lipids represent5 to 10% of the dry mass of most cells, and storage lipids, more than50% of the mass of an adipocyte.
With some important exceptions,these lipids play a passive role in the cell; fuels are acted on by oxidative enzymes, and lipid membranes form impermeable barriers thatseparate cellular compartments. Another group of lipids, although relatively minor cellular components on a mass basis, have specific andessential biological activities. These include hundreds of steroids—compounds that share the four-ring steroid nucleus but are more polarthan cholesterol—and large numbers of isoprenoids, which are synthesized from five-carbon precursors related to isoprene:CH3IsopreneCH 2 =C—CH=CH 2The isoprenoids include vitamins A, D, E, and K, first recognized asfatty materials essential to the normal growth of animals, and numerous biological pigments. Other "active" lipids serve as essential cofactors for enzymes, as electron carriers, or as intracellular signals.
Toillustrate the range of their structures and biological activities we willbriefly describe a few of these compounds. In later chapters, their synthesis and biological roles will be considered in more detail.Steroid Hormones Carry Messages between TissuesThe major groups of steroid hormones are the male and female sexhormones and the hormones of the adrenal cortex, cortisol and aldosterone (Fig. 9-15). All of these hormones contain an intact steroid nucleus. They are produced in one tissue and carried in the bloodstreamto target tissues, where they bind to highly specific receptor proteinsand trigger changes in gene expression and metabolism. Because of thevery high affinity of receptor for hormone, very low concentrations ofhormone (as low as 10~9 M) suffice to produce the effect on target tissues.
These hormones and their actions are described in more detail inChapter 22.Chapter 9 LipidsTestosteroneEstradiolCHoOH257Figure 9-15 Steroids derived from cholesterol.Testosterone, the male sex hormone, is produced inthe testes. Estradiol, one of the female hormones, isproduced in the ovaries and placenta.
Cortisol andaldosterone are hormones produced in the cortex ofthe adrenal gland; they regulate glucose metabolism and salt excretion, respectively.C=OCortisolAldosteroneHydrolysis of Phosphatidylinositol ProducesIntracellular MessengersPhosphatidylinositol and its phosphorylated derivatives (Fig. 9-16)are components of the plasma membranes of all eukaryotic cells. Theyserve as a reservoir of messenger molecules that are released insidethe cell when certain extracellular signals interact with specific receptors in the plasma membrane. For example, when the hormone vasopressin binds to receptor molecules in the plasma membranes of cellsin the kidney and the blood vessels, a specific phospholipase in themembrane is activated.
This phospholipase breaks the bond betweenglycerol and phosphate in phosphatidylinositol-4,5-bisphosphate (Fig.9-16), releasing two products: inositol-l,4,5-trisphosphate and diacylglycerol. Inositol-l,4,5-trisphosphate causes the release of Ca 2+ sequestered in membrane-bounded compartments of the cell, triggering theactivation of a variety of Ca 2+ -dependent enzymes and hormonal responses.
Diacylglycerol binds to and activates an enzyme, protein kinase C, that transfers phosphate groups from ATP to several cytosolicproteins, thereby altering their enzymatic activities.Figure 9-16 Phosphatidylinositol-4,5-bisphosphate,formed in the plasma membrane by phosphorylation of phosphatidylinositol, is hydrolyzed by a specific phospholipase C in response to hormonal signals. Both of the products of hydrolysis act asintracellular messengers.Phosphatidylinositolphosphorylation ^- 2ATPin plasmamembrane^2ADPPhosphatidylinositol-4,5-bisphosphatehormone-sensitivephospholipase Cin plasmamembraneH2ODiacylglycerolInositol-l,4,5-trisphosphateActivation ofprotein kinase CRelease of intracellular Ca2+Enzyme activationEnzymeactivationOther hormonalresponses258Membranephospholipid0^Leukotriene A4Figure 9-17 Arachidonic acid and some of itseicosanoid derivatives.
In response to certain hormonal signals, phospholipase A2 releases arachidonic acid (arachidonate at pH 7) from membranephospholipids; arachidonic acid then serves as aprecursor to various eicosanoids. These includeprostaglandins such as PGEi, in which carbonatoms 8 and 12 of arachidonic acid are joined toform the characteristic five-membered ring; thromboxane A2, in which carbons 8 and 12 are joinedand an oxygen atom is added to form the sixmembered ring; and leukotriene A, containing aseries of three conjugated double bonds. Aspirinand ibuprofen block the formation of prostaglandinsand thromboxanes from arachidonic acid.OHThromboxane A2Eicosanoids Are Potent Biological EffectorsEicosanoids (Fig.
9-17) are fatty acid derivatives with a variety of extremely potent hormonelike actions on various tissues of vertebrateanimals. Unlike hormones, they are not transported between tissues inthe blood, but act on the tissue in which they are produced. This familyof compounds is known to be involved in reproductive function; in theinflammation, fever, and pain associated with injury or disease; in theformation of blood clots and the regulation of blood pressure; in gastricacid secretion; and in a variety of other processes important in humanhealth or disease.
More roles for the eicosanoids doubtless remain to bediscovered.Eicosanoids are all derived from the 20-carbon polyunsaturatedfatty acid arachidonic acid, 20:4(A 5 ' 81114 ) (Fig. 9-17), from which theytake their general name (Greek eikosi, "twenty"). There are threeclasses of eicosanoids: prostaglandins, thromboxanes, and leukotrienes.
Various eicosanoids are produced in different cell types by different synthetic pathways, and have different target cells and biological actions.The prostaglandins (PG) (Fig. 9-17) all contain a five-memberedring of carbon atoms originally part of the chain of arachidonic acid.They derive their name from the tissue in which they were first recognized (the prostate gland). Two groups were originally defined: PGE,for ether-soluble, and PGF, for phosphate buffer-soluble (fosfat inSwedish). Each contains numerous subtypes, named PGEi, PGE2, etc.Prostaglandins are now known to act in many tissues by regulating thesynthesis of the intracellular messenger molecule 3',5'-cyclic AMP(cAMP). Because cAMP mediates the action of many hormones, theprostaglandins affect a wide range of cellular and tissue functions.Some prostaglandins stimulate contraction of the smooth muscle of theuterus during labor or menstruation.
Others affect blood flow to specific organs, the wake-sleep cycle, and the responsiveness of certaintissues to hormones such as epinephrine and glucagon. Prostaglandinsin a third group elevate body temperature (producing fever) and causeinflammation, resulting in pain.Chapter 9 Lipids259The thromboxanes, first isolated from blood platelets (alsoknown as thrombocytes), have a six-membered ring containing anether (Fig. 9-17).
They are produced by platelets and act in formationof blood clots and the reduction of blood flow to the site of a clot.Leukotrienes, found first in leukocytes, contain three conjugateddouble bonds (Fig. 9-17). They are powerful biological signals; for example, they induce contraction of the muscle lining the airways to thelung. Overproduction of leukotrienes causes asthmatic attacks. Thestrong contraction of the smooth muscles of the lung that occurs duringanaphylactic shock is part of the potentially fatal allergic reaction inindividuals hypersensitive to bee stings, penicillin, or various otheragents.Vitamins A, D, E, and K Are Fat-SolubleDuring the first third of this century, a major focus of research inphysiological chemistry was the identification of vitamins—compounds essential to the health of humans and other vertebrateanimals that cannot by synthesized by these animals and must therefore be obtained in the diet. Early nutritional studies identified twogeneral classes of such compounds: those soluble in nonpolar organicsolvents (fat-soluble vitamins) and those that could be extracted fromfoods with aqueous solvents (water-soluble vitamins).
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