Lipids
• Terpenes: isoprene units, classification,variations
• Isopentenyl
pyrophosphatebiosynthesis from acetategeneral reactivity
• C-C bond formation in terpene
biosynthesiscarbocation intermediate, extension,synthesis higher terpenes, synthesiscyclic structures
• Cholesterolconfiguration, structure, biosynthesis,intermediate for: vitamin D, bile acids,
corticosteroids, sex hormones• Carotenoids
Terpenes: The Isoprene Rule
Terpenes
and terpenoids
are the most important constituents in essential oils
Terpenes
are built from C5
isoprene units
Isoprene units are linked head-to-tail
tail
head
Isoprene(2-methyl-1,3-butadiene)
H2CC
CH3
CH
CH2 =
Terpenes
are repeating isoprene units
Classified according to the number of isoprene units they contain
Class # Isoprene units # C atoms
Monoterpene Sesquiterpene Diterpene Sesterpene Triterpene Tetraterpene
234568
101520253040
OHFarnesol
(terpenoid)
Terpenes
may be substituted, cyclic, orlinked tail-to-tail
Squalene(from shark liver oil)
tail
tail
Selinene(from celery oil)
Limonene(from lemon or orange oil)
OH
Menthol(from peppermint)
OH
Vitamin A
Isopentenyl pyrophosphate
Isoprenoid compounds are synthesized from acetate!!
Early steps are analogous to fatty acid biosynthesis except no ACP
SCoA
O
Acetyl coenzyme A
+-O
O
SCoA
O
Malonylcoenzyme A
O
SCoA
O
Acetoacetylcoenzyme A
+ CO2
+ CoASH
O
SCoA
O
Acetoacetylcoenzyme A
+SCoA
O
Acetylcoenzyme A
OH
SCoA
O
O
OH
3-Hydroxy-3-methylglutarylcoenzyme A (HMG CoA)
+ CoASH
Enzymaticreduction
OH
OH
O
OH
Mevalonic acid
HO OH
O
HO
Isopentenyl pyrophosphate:The biological isoprene unit
Mevalonate
-O OH
O
HO
Enzymaticphosphorylation
-O OPOPOH
O
2-O3PO
- PO43-
- CO2
OPPCCH2CH2OPOPOHH2C
CH3 O
OH
O
OH
Isopentenyl pyrophosphate
isopentenyl diphosphate isomeraseEnz-H
H HOPP
Enz
Carbocation intermediate
OPP
+ Enz-H
Dimethylallylpyrophosphate
O
OH
O
OH
Structurally similar but different chemical reactivity
OPP OPP
Dimethylallylpyrophosphate
(reactive allylic C)
Isopentenylpyrophosphate(reactive C=C)
Nu
good leaving group
E+
OPPOPP+
OPP + OPPpyrophosphate ion
OPP
- [ OPP]
OPP
OPP
C-C in Terpene Biosynthesis
10-C cation
is the same whether 1 step or 2 steps
10-C intermediate undergoestypical carbocation reactions
OPPH H
Enz-
OPP
Geranyl pyrophosphate(allylic pyrophosphate)
H2O
OHGeraniol
(monoterpene in rose oil)
OPP
Geranyl pyrophosphate
OPPEnz
OPP
15-C carbocation
[deprotonation]
OPPFarnesyl pyrophosphate
H2O
OHFarnesol
Geranylgeraniol
Higher terpenes
formed from couplingof terpenes
via another mechanism, not successive addition of C5
units
OPPFarnesyl pyrophosphate
2
Triterpene C30
(tail to tail coupling)
Steroids
OPP
"E" "Z"
OPP
Enz. c
at.
isom
eriz
atio
n
3o carbocation
- H+
H2O
LimoneneOH
bicyclic carbocation
- H+
-pinene -pinene
+
intramolecularattack
figure 26.6capture by H2O and
rearrangement
Summary
Terpene
and steroid biosynthetic paths
Geranyl pyrophosphate(C10-pyrophosphate)
Farnesyl pyrophosphate(C15-pyrophosphate)
C20-Pyrophosphate
Tetraterpenes(C40)
3-methyl-3-butenylpyrophosphate
3-methyl-3-butenylpyrophosphate
Squalene(C30)
Lanosterol
Cholesterol(a steroid)
Monoterpenes(C10)
Sesquiterpenes(C15)
Diterpenes(C20)
Steroids: Cholesterol
A B
C D
CH3
CH3
HH
R
A BC D
5 series (trans)
5
CH3
CH3
H
R
BC D
5H
5 series (cis)
A
HO
H
H
H
Cholesterol
• The most abundant steroid in humans• All other steroids arise from cholesterol
• The average adult has >200g • It is in almost all body tissues• Animals acquire cholesterol from their
diet, but can synthesize all they needfrom acetate
Synthesis from acetate
Squalene
O2, NADHmonooxygenase
O
epoxide ring opening
carbocation reactions* p. 1133
HO
H
H
H
Cholesterol
Cholesterol
Steroids
Bile acids
Vitamin D
Sex hormones
Corticosteroids
Reactions
Cholesterol is a precursor to other lipids
Vitamin D
From enzymatic oxidation of cholesterol to 7-dehydrocholesterol
Present in skin and converted to vitamin D by sunlight
Important in Ca2+
absorption
HO
H H
7-Dehydrocholesterol
HO
H H
sunlight
Vitamin D3
Bile Acids
Bile salts: amide derivativesBottom face polar; top face non-polarEmulsify fats by forming micelles where
fats on inside and bile salts on outside
FAT
salts
H2 O
Micelle fig. from Mol. Cell. Biol.
O
H
H
H
X = OH; Cholic AcidX = NHCH2CH2SO3Na; Sodium taurocholate (bile salt)
HOH OH
OHX
Corticosteroids
Many physiological effects, ie. maintainelectrolyte balance; regulate carb, lipid,protein metabolism; mediate allergic and inflammatory response
Cortisol
most abundantCortisone –
antiinflammatory
drug
H
H
H
Cortisol
O
O
HO OH
OH
H
H
H
Cortisone
O
O
OH
OH
O
Sex hormones
Regulate biological processes
•
Male –
androgens
(testes)•
Female –
estrogens
(ovaries) •
Pregnancy –
progestins
OH
H
H
H
Testosterone
O
OH
H
H
H
Estradiol
HO
H
H
H
ProgesteroneO
O
Cholesterol