Transcript Chemdraw B&W - Pennsylvania State University

Chapter 27. Biomolecules: Lipids
Based on McMurry’s Organic Chemistry, 6th edition
About Lipids
• Naturally materials that preferentially extract into
nonpolar organic solvents
• Includes fats, oils, waxes, some vitamins and
hormones, some components of membrane
• General types: esters (“saponifiable”) and those that
can’t be hydrolyzed
27.1 Waxes, Fats, and Oils
• Waxes - contain esters formed from long-chain (C16C36) carboxylic acids and long-chain alcohols (C24C36)
• Triacontyl hexadecanoate is in beeswax
Fats and Oils
• Animal fats and vegetable are triacylglycerols oil
– Triesters of glycerol with three long-chain carboxylic acids
• Saponification of a fat or oil with (reaction with
aqueous NaOH) yields glycerol and three fatty acids
Fatty Acids (from Fats and Oils)
• Straight-chain (C12 - C20) carboxylic acids
• Double bonds are cis-substituted but trans-fatty acid
also occur
• A fat or oil in nature occurs as a mixture of many
different triacylglycerols
• The most abundant saturated fatty acids are palmitic
(C16) and stearic (C18)
Unsaturated and Polyunsaturated
Fatty Acids
• Oleic (C18 with one C=C) and linolenic (C18 with 3 C=C)
are the most abundant unsaturated
27.2 Soap
• A mixture of sodium or potassium salts of long-chain
fatty acids produced by alkaline hydrolysis
(saponification) of animal fat with alkali
Cleansing Action of Soap
• The carboxylate end of the long-chain molecule is ionic
and therefore is preferentially dissolved in water
• The hydrocarbon tail is nonpolar and dissolves in
grease and oil
• Soaps enable grease to be dissolved into water
Detergents
• “Hard” water contains Mg+2 and Ca+2 that form
insoluble salts with soaps
• Synthetic detergents are alkylbenzene sulfonates that
dissolve dirt like soaps but do not form scums with
Mg+2 and Ca+2 .
27.3 Phospholipids
• Phospholipids are diesters of H3PO4, phosphoric acid
• Phosphoric acid can form monoesters, diesters and
triesters
• In general these are known as “phosphates”
Phosphoglycerides
• Contain a glycerol backbone linked by ester bonds to
two fatty acids and phosphoric acid
• Fatty acid residues with C12–C20
• The phosphate group at C3 has an ester link to an
amino alcohol
Phosphoglyceride Membranes
• Phosphoglycerides comprise the major lipid
component of cell membranes
• Nonpolar tails aggregate in the center of a bilayer
• Ionic head is exposed to solvent
Sphingolipids
• The other major group of phospholipids
• Sphingosine or a dihydroxyamine backbone
• Constituents of plant and animal cell membranes
• Abundant in brain and nerve tissue, as coating around
nerve fibers.
27.4 Prostaglandins
• C20 lipids that contain a five-membered ring with two
long side chains
• Present in small amounts in all body tissues and fluids
• Many physiological effects
Prostaglandin Sources
• Biosynthesized from arachidonic acid (C20
unsaturated fatty acid)
• Catalyzed by cyclooxygenase (COX)
27.5 Terpenoids
• Steam distillation of plant extracts produces “essential
oils”
• Chemically related to compounds in turpentine (from
pine sap) called terpenes and thus called terpenoids
• Mostly hydrocarbons (some oxygens) that do not
contain esters (stable to hydrolysis)
Terpenoids Are Isoprenoids
• Terpenoid structures are derived from isoprene (2methyl-1,3-butadiene) units connected head-to-tail
(Isoprene Rule)
• The term “head-to-tail” means that dissimilar ends are
connected (you can choose which is a “head” and
which is a “tail”)
Classification of Terpenoids
• Classified according to the number of di-isoprenoid
(C10) units they contain
• Monoterpenes have 10-carbons, sesquiterpenes
(sesqui = 1 1/2) have 15-carbons from three isoprene
units, and so on
Some Important Terpenoids
• The triterpene lanosterol is the precursor of
steroid hormones
• The tetraterpene b-carotene is a source of
vitamin A
27.6 Biosynthesis of Terpenoids
• Isopentenyl pyrophosphate (IPP) forms higher
isoprenoids in reactions catalyzed by prenyl
transferase
• Monoterpenoids, diterpenoids, and tetraterpoids arise
from 1-deoxyxylulose 5-phosphate.
Mevalonate Pathway to
Isopentenyl Diphosphate
• Begins with the conversion of acetate to acetyl CoA
followed by Claisen condensation to yield acetoacetyl
CoA
• Catalyzed by acetoacetyl-CoA acetyltransferase
Aldol Condensation Produces
HMG-CoA
• Carbonyl condensation reaction of acetoacetyl CoA with
acetyl CoA
• Produces 3-hydroxy-3-methylglutaryl CoA (HMG-CoA)
Reduction Forms Mevalonate
• HMG CoA is reduced to mevalonate
• Catalyzed by HMG CoA reductase utilizing NADPH
Conversion of Mevalonate to
IPP
• Pyrophosphorylation gives mevalonyl-PP
• Addition of phosphate from ATP followed by loss of
CO2 and phosphate
Conversion of Isopentenyl
Diphosphate to Terpenoids
• For triterpenes and larger, head-to-head coupling of
farnesyl diphosphates gives squalene
Mechanism of Isomerization
• Isomerization of IPP to DMAPP is catalyzed by IPP
isomerase through a carbocation pathway
Coupling Mechanism
• Nucleophilic substitution reaction in which the double
bond of IPP behaves as a nucleophile in displacing
diphosphate ion leaving group (PPO)
Conversions of
Monoterpenoids
• Typically involves carbocation intermediates and
multistep reaction pathways catalyzed by a terpene
cyclase
27.7 Steroids
• Steroids,are another class of nonsaponifiable lipid,
defined by structure
• Has four fused rings A, B, C, and D, beginning at the
lower left
• Carbon atoms are numbered beginning in the A ring
• The six-membered rings are in fixed chair
conformations
Functions of Steroids
• In humans as hormones, steroids are chemical
messengers secreted by glands and carried through
the bloodstream to target tissues
• Also widely distributed as cholesterol
Male Sex Hormones
• Testosterone and androsterone are the two most
important male sex hormones, or androgens
• Androstanedione is a precursor
Female Sex Hormones
• Estrone and estradiol are the two most important
female sex hormones, or estrogens
• Progesterone is the most important progestin, steroids
that function in pregnancy
Adrenocortical Hormones
• Adrenocortical steroids: secreted by the adrenal
glands near the upper end of each kidney
• Mineralocorticoids: control tissue swelling by
regulating cellular salt balance
• Glucocorticoids: regulation of glucose metabolism and
in the control of inflammation
Synthetic Steroids
• Made in pharmaceutical laboratories as new drugs
• Includes oral contraceptives and anabolic agents
• Methandrostenolone is an anabolic steroid used for
tissue-building
27.8 Stereochemistry of
Steroids
• Two cyclohexane rings can be joined in either a cis or a
trans manner
• In cis-decalin, both groups at the ring-junction
positions are on the same side of the two rings
• In trans-decalin, the groups at the ring junctions are on
opposite sides
A/B Junction in Steroids
• Steroids can have either a cis or a trans fusion of the A
and B ring
• (B–C and C–D) are usually trans
27.9 Steroid Biosynthesis
• Enzyme-catalyzed addition of oxygen atom to squalene
• Stereospecific formation of an oxirane from an alkene
R
R
O2
Enzyme
O
Squalene
2,3-Oxidosqualene
Cyclization to Steroid
• Stork-Eschenmoser mechanism
• Enzyme-catalyzed
• See Figure 27.6
R
O
E-H
HO
R
protosteryl cation