3 Биологические мембраны. Обмен веществом (1160072), страница 6
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Eventually thefat-soluble group was resolved into the four vitamins A, D, E, and K, allof which are isoprenoid compounds. Isoprenoids are synthesized by thecondensation of isoprene units.Vitamin A (retinol) (Fig. 9-18) is a pigment essential to vision. Itwas first recognized as an essential nutritional factor for laboratoryanimals, and was later isolated from fish liver oils. Vitamin A itselfCH 3Figure 9—18 Vitamin Aj and its precursor,/3-carotene.
The isoprene structural units are setoff by dashed red lines. Cleavage of /3-caroteneyields two molecules of vitamin A1 (retinol). Oxidation at C-15 converts retinol to the aldehyde, retinal. Rhodopsin, a visual pigment widely employedin nature, consists of retinal and the protein opsin.In the dark, retinal of rhodopsin is in the 11-cisform. When a rhodopsin molecule is excited withvisible light, the 11-cis -retinal undergoes a series ofphotochemical reactions that convert it to a\\-transretinal, forcing a change in the shape of the entirerhodopsin molecule. This transformation in the rodcell of the vertebrate retina leads to an electricalsignal to the brain that is the basis of visualtransduction.visiblelightNeuralsignalto brainoxidation ofalcohol toaldehyde•CH315 CH 2 OHVitamin AT(retinol)/3-CaroteneCH.CHORhodopsin (11-cis-retinal,bound to the protein opsin)CHOActivated rhodopsin260Part II Structure and CatalysisCH aHCH-CH 2 —CH 2 —CH 2 -C—CHIICH|C37-DehydrocholesterolUV lightCH 3IH25 Idoes not occur in plants, but many plants contain carotenoids, lightabsorbing pigments that can be enzymatically converted into vitaminA by most animals.
Figure 9-18 shows, for example, how vitamin A canbe formed by cleavage of /3-carotene, the pigment that gives carrots,sweet potatoes, and other yellow vegetables their characteristic color.Deficiency of vitamin A leads to a variety of symptoms in humans andexperimental animals, which include dry skin, xerophthalmia (dryeyes), dry mucous membranes, retarded development and growth, sterility in male animals, and night blindness, an early symptom commonly used in the medical diagnosis of vitamin A deficiency.Vitamin D is a derivative of cholesterol and the precursor to ahormone essential in calcium and phosphate metabolism in vertebrateanimals. Vitamin D3, also called cholecalciferol, is normally formed inthe skin in a photochemical reaction driven by the ultraviolet component of sunlight (Figure 9-19). It is also abundant in fish liver oils, andis added to commercial milk as a nutritional supplement. Vitamin D3itself is not biologically active, but it is the precursor of 1,25-dihydroxycholecalciferol, a potent hormone that regulates the uptake of calciumin the intestine and the balance of release and deposition of bone calcium and phosphate.
Deficiency of vitamin D leads to defective boneformation, resulting in the disease rickets.Vitamin E (Fig. 9-20) is the collective name for a group of closelyrelated lipids called tocopherols, all of which contain a substituted aromatic ring and a long hydrocarbon side chain. Tocopherols are found inhens' eggs and vegetable oils, and are especially abundant in wheatgerm. Deficiency of vitamin E is very rare in humans, but when laboratory animals are fed diets depleted of vitamin E, they develop scalyskin, muscular weakness and wasting, and sterility.
Tocopherols canundergo oxidation-reduction reactions on the aromatic ring. The vitamin activity of tocopherols likely results from their ability to preventoxidative damage to the lipids of cellular membranes. Recall the reactions of unsaturated fatty acids with oxygen that cause rancidity infoods.
If such reactions were to occur in living cells, the resulting defects in membrane function might cause cell death. Tocopherols reactwith and destroy the most reactive forms of oxygen, protecting unsaturated fatty acids from oxidation. Tocopherols are used commercially toretard spoilage of certain foods.Vitamin K is a lipid cofactor required for normal blood clotting.Vitamin Kx (phylloquinone; Fig. 9-20) is found in green plant leaves,CH—CH 2 -CH 2 —CH 2 —C—CH 3CH 3Vitamin D3(cholecalciferol)liver enzyme oxidizes C-25kidney enzyme oxidizes C-lOHIHOCH 31,25-DihydroxycholecalciferolFigure 9—19 Vitamin D3 production and metabolism. Vitamin D3 is produced by irradiation of7-dehydrocholesterol in the skin, and in the kidneyis converted into the active hormone, 1,25-dihydroxycholecalciferol, which regulates the metabolism ofCa2+ and POI".
Dietary vitamin D prevents rickets, a disease once common in cold climates, whereheavy clothing blocked the UV component of sunlight necessary to vitamin D3 production in skin.Chapter 9 LipidsCH 3CH 3CH 3CH2-CH2-CH2-CH-CH2-UCH2-CH2-CH-CH2-CH2-CH2-CH-CH3CH 3CH 3261CH 3Vitamin E: an antioxidantCH 3CH2-CH=C-CH2-(cH2-CH2-CH-CH2)2-)-CH2-CH2-CH-CH3Vitamin K^ a blood-clotting cofactor(phylloquinone)Figure 9-20 Some other biologically active isoprenoid compounds or derivatives. Note that the values of n exclude the first and last isoprene unit ineach isoprenoid side chain as represented here.Warfarin does not occur naturally.
It is an analogof vitamin K that lacks an isoprenoid side chain.Warfarin: a blood anticoagulantCH,CH 3CH 3CH 2 -CH=C-CH 2 — CH 2 -CH=C-CHCH 3CH 3Ubiquinone: a mitochondrial electron carrierCH3(coenzyme Q)|-CH 2 -CH=C—CH 3CH,Plastoquinone: a chloroplast electron carrierC H 2 - C H = C - C H 2 - CH 2 -CH=C-CH 2 L - C H 2 - C H = C - C H 3 (n = 4-8)CH 3CH 3CH 3'I/I\|HO^-CH2-CH2-CH-CH2-(CH2-CH=C-CH2jn-CH2-CH=C-CH3and a related form, vitamin K2 (menaquinone), is formed by bacteriaresiding in the animal intestine. The vitamin acts in the formation ofprothrombin, a blood plasma protein essential in blood-clot formation.Prothrombin is a proteolytic enzyme that splits specific peptide bondsin the blood protein fibrinogen, converting it to fibrin, the insoluble,fibrous protein that holds blood clots together.
Deficiency of vitamin Kresults in slowed blood clotting, which can be fatal to a wounded animal. Henrik Dam and Edward A. Doisy are given credit for havingindependently discovered the antihemorrhaghic action of vitamin K.Warfarin (Fig. 9-20) is a synthetic analog of vitamin K, which actsas a competitive inhibitor of prothrombin formation. It is extremelypoisonous to rats, causing death by internal bleeding. Ironically, thispotent rodenticide is also a valuable anticoagulant drug for the treatment of human patients in whom excessive blood clotting is dangerous—surgical patients and victims of coronary thrombosis.Dolichol: a sugar carrierin = 9-22)Henrik Dam1895-1976Edward A.
Doisy1893-1986262Part II Structure and CatalysisLipid Quinones Carry ElectronsUbiquinone and plastoquinone (Fig. 9-20), also isoprenoid derivatives,function as electron carriers in the production of ATP in mitochondriaand chloroplasts. In most mammalian tissues, ubiquinone (also calledcoenzyme Q) has ten isoprene units. Plastoquinone is the plant equivalent of ubiquinone.
In their roles as electron carriers, both ubiquinoneand plastoquinone can accept either one or two electrons and eitherone or two protons to be reduced, as shown in Figure 18-2.Dolichols Form Activated, Hydrophobic Sugar DerivativesDuring the assembly of the complex carbohydrates of bacterial cellwalls, and during the addition of polysaccharide units to certain proteins (glycoproteins) in eukaryotes, the sugar units to be added arechemically activated by attachment to dolichols (Fig. 9-20), anothergroup of isoprenoids. Dolichols from animals have between 17 and 21isoprene units (85 to 105 carbon atoms), bacterial dolichols have 11units, and those of plants and fungi have 14 to 24 isoprene units.
Thesevery hydrophobic compounds have strong hydrophobic interactionswith membrane lipids, anchoring the attached sugars to the membrane where they participate in sugar-transfer reactions.Resolution and Analysis of LipidsIn exploring the role of lipids in a biological process, it is often useful toknow which lipids are present, and in what proportions. Because lipidsare insoluble in water, their extraction from tissues and subsequentfractionation require the use of organic solvents and some techniquesnot commonly used in the purification of water-soluble molecules suchas proteins and carbohydrates.
In general, complex mixtures of lipidsare separated by differences in their polarity or solubility in nonpolarsolvents. Lipids that contain ester- or amide-linked fatty acids can behydrolyzed (saponified) by treatment with acid or alkali, to yield theircomponent parts for analysis.Lipid Extraction Requires Organic SolventsNeutral lipids (triacylglycerols, waxes, pigments, etc.) are readily extracted from tissues with ethyl ether, chloroform, or benzene, solventsin which lipid clustering driven by hydrophobic interactions does notoccur. Membrane lipids are more effectively extracted by more polarorganic solvents, such as ethanol or methanol, which reduce the hydrophobic interactions among lipid molecules but also weaken the hydrogen bonds and electrostatic interactions that bind membrane lipids tomembrane proteins.
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