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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
'!Leukotrienes
Leukotrienes, first found in leukocytes, contain three conjugated double bonds. They are powerful
biological signals. For example, leukotriene D4, derived from leukotriene A4, induces contraction of the
muscle lining the airways to the lung. Overproduction of leukotrienes causes asthmatic attacks, and
leukotriene synthesis is one target of antiasthmatic drugs such as prednisone. The strong contraction
of the smooth muscles of the lung that occurs during anaphylactic shock is part of the potentially fatal
allergic reaction in individuals hypersensitive to bee stings, penicillin, or other agents.
) &
Steroids are oxidized derivatives of sterols; they have the sterol nucleus but lack the alkyl chain
attached to ring D of cholesterol, and they are more polar than cholesterol. Steroid hormones move
through the bloodstream (on protein carriers) from their site of production to target tissues, where they
enter cells, bind to highly specific receptor proteins in the nucleus, and trigger changes in gene
expression and metabolism. Because hormones have very high affinity for their receptors, very low
concentrations of hormones (nanomolar or less) are sufficient to produce responses in target tissues.
The major groups of steroid hormones are the male and female sex hormones and the hormones
produced by the adrenal cortex, cortisol and aldosterone (Fig. 10–19). Prednisone and prednisolone
are steroid drugs with potent antiinflammatory activities, mediated in part by the inhibition of
arachidonate release by phospholipase A2 (Fig. 10–18) and consequent inhibition of the synthesis of
leukotrienes, prostaglandins, and thromboxanes. They have a variety of medical applications,
including the treatment of asthma and rheumatoid arthritis.
D( A
'D
Vitamin D3, also called cholecalciferol, is normally formed in the skin from 7-dehydrocholesterol in a
photochemical reaction driven by the UV component of sunlight (Fig. 10–20). Vitamin D3 is not itself
biologically active, but it is converted by enzymes in the liver and kidney to 1,25-
dihydroxycholecalciferol, a hormone that regulates calcium uptake in the intestine and calcium levels
in kidney and bone. Deficiency of vitamin D CH3 C Isoprene CH CH2 CH2 leads to defective bone formation
and the disease rickets, for which administration of vitamin D produces a dramatic cure. Vitamin D2
(ergocalciferol) is a commercial product formed by UV irradiation of the ergosterol of yeast. Vitamin D2
is structurally similar to D3, with slight modification to the side chain attached to the sterol D ring. Both
have the same biological effects, and D2 is commonly added to milk and butter as a dietary
supplement. Like steroid hormones, the product of vitamin D metabolism, 1,25-
dihydroxycholecalciferol, regulates gene expression—for example, turning on the synthesis of an
intestinal Ca2_-binding protein.
'A
Vitamin A (retinol) in its various forms functions as a hormone and as the visual pigment of
the vertebrate eye (Fig. 10–21). Acting through receptor proteins in the cell nucleus, the
vitamin A derivative retinoic acid regulates gene expression in the development of epithelial
tissue, including skin. Retinoic acid is the active ingredient in the drug tretinoin (Retin-A),
used in the treatment of severe acne and wrinkled skin. The vitamin
A derivative retinal is the pigment that initiates the response of rod and cone cells of the
retina to light, producing a neuronal signal to the brain. This role of retinal is described in
detail in Chapter 12. Vitamin A was first isolated from fish liver oils; liver, eggs, whole milk,
and butter are good dietary sources. In vertebrates, _-carotene, the pigment that gives
carrots, sweet potatoes, and other yellow vegetables their characteristic color, can be
enzymatically converted to vitamin A. Deficiency of vitamin A leads to a variety of symptoms
in humans, including dryness of the skin, eyes, and mucous membranes; retarded
development and growth; and night blindness, an early symptom commonly used in
diagnosing vitamin A deficiency.
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Lehninger: Principles of Biochemistry (3rd edition)
( K( E
'E
Vitamin E is the collective name for a group of closely related lipids called tocopherols, all of which
contain a substituted aromatic ring and a long isoprenoid side chain (Fig. 10–22a). Because they are
hydrophobic, tocopherols associate with cell membranes, lipid deposits, and lipoproteins in the blood.
Tocopherols are biological antioxidants. The aromatic ring reacts with and destroys the most reactive
forms of oxygen radicals and other free radicals, protecting unsaturated fatty acids from oxidation and
preventing oxidative damage to membrane lipids, which can cause cell fragility. Tocopherols are
found in eggs and vegetable oils and are especially abundant in wheat germ. Laboratory animals fed
diets depleted of vitamin E develop scaly skin, muscular weakness and wasting, and sterility. Vitamin
E deficiency in humans is very rare; the principal symptom is fragile erythrocytes.
'K
The aromatic ring of vitamin K (Fig. 10–22b) undergoes a cycle of oxidation and reduction during the
formation of active prothrombin, a blood plasma protein essential in blood clot formation. Prothrombin
is a proteolytic enzyme that splits peptide bonds in the blood protein fibrinogen to convert it to fibrin,
the insoluble fibrous protein that holds blood clots together. Henrik Dam and Edward A. Doisy
independently discovered that vitamin K deficiency slows blood clotting, which can be fatal. Vitamin K
deficiency is very uncommon in humans, aside from a small percentage of infants who suffer from
hemorrhagic disease of the newborn, a potentially fatal disorder. In the United States, newborns are
routinely given a 1 mg injection of vitamin K. Vitamin K1 (phylloquinone) is found in green plant leaves;
a related form, vitamin K2 (menaquinone), is formed by bacteria residing in the vertebrate intestine.
'Wafarin
Warfarin (Fig. 10–22c) is a synthetic compound that inhibits the formation of active prothrombin. It is
particularly poisonous to rats, causing death by internal bleeding. Ironically, this potent rodenticide is
also an invaluable anticoagulant drug for treating humans at risk for excessive blood clotting, such as
surgical patients and those with coronary thrombosis.
# Dolichols
During assembly of the complex carbohydrates of bacterial cell walls, and during the addition of
polysaccharide units to certain proteins (glycoproteins) and lipids (glycolipids) in eukaryotes, the
sugar units to be added are chemically activated by attachment to isoprenoid alcohols called
dolichols (Fig. 10–22f). These compounds have strong hydrophobic interactions with membrane
lipids, anchoring the attached sugars to the membrane, where they participate in sugar-transfer
reactions.
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Lehninger: Principles of Biochemistry (3rd edition)
Preparatory Phase
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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Lehninger: Principles of Biochemistry (3rd edition)
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