These reactions Figure 24.12 are essentially a reversal of fatty acid oxidation, with the exception that NADPH is utilized in the saturation of the double bond, instead of FADH2.. Unsatu
Trang 1C16Fatty Acids May Undergo Elongation and Unsaturation
Additional Elongation As seen already, palmitate is the primary product of the
fatty acid synthase Cells synthesize many other fatty acids Shorter chains are
eas-ily made if the chain is released before reaching 16 carbons in length Longer
chains are made through special elongation reactions, which occur both in the
mitochondria and at the surface of the endoplasmic reticulum (ER) The ER
re-actions are actually quite similar to those we have just discussed: addition of
two-carbon units at the carboxyl end of the chain by means of oxidative
decarboxyla-tions involving malonyl-CoA As was the case for the fatty acid synthase, this
decarboxylation provides the thermodynamic driving force for the condensation
reaction The mitochondrial reactions involve addition (and subsequent
reduc-tion) of acetyl units These reactions (Figure 24.12) are essentially a reversal of
fatty acid oxidation, with the exception that NADPH is utilized in the saturation
of the double bond, instead of FADH2
Introduction of a Single cis Double Bond Both prokaryotes and eukaryotes are
capable of introducing a single cis double bond in a newly synthesized fatty acid.
Bacteria such as E coli carry out this process in an O2-independent pathway,
whereas eukaryotes have adopted an O2-dependent pathway There is a
fundamen-tal chemical difference between the two The O2-dependent reaction can occur
any-where in the fatty acid chain, with no (additional) need to activate the desired bond
toward dehydrogenation However, in the absence of O2, some other means must
be found to activate the bond in question Thus, in the bacterial reaction,
dehy-drogenation occurs while the bond of interest is still near the -carbonyl or
-hydroxy group and the thioester group at the end of the chain.
C
CH2
C H
OH
C
H
H
CH2
C
O
O O
O
H +
1
4
2
3 Acyl-CoA
Acyl-CoA (2 carbons longer)
Thiolase HSCoA
-Ketoacyl-CoA
L --hydroxyacyl-CoA
dehydrogenase
L--Hydroxyacyl-CoA
, -trans-Enoyl-CoA
Enoyl-CoA hydratase
NADH +
NAD+
NADPH +
NADP+
H2O
H +
FIGURE 24.12 (1) Elongation of fatty acids in mitochondria
is initiated by the thiolase reaction The -ketoacyl
intermediate thus formed undergoes the same three reac-tions (in reverse order) that are the basis of -oxidation of
fatty acids (2) Reduction of the -keto group is followed
by (3) dehydration to form a double bond (4) Reduction
of the double bond yields a fatty acyl-CoA that is elon-gated by two carbons Note that the reducing coenzyme for the second step is NADH, whereas the reductant for the fourth step is NADPH.
Trang 2734 Chapter 24 Lipid Biosynthesis
In E coli, the biosynthesis of a monounsaturated fatty acid begins with four normal
cycles of elongation to form a ten-carbon intermediate, -hydroxydecanoyl-ACP
(Fig-ure 24.13) At this point, -hydroxydecanoyl thioester dehydrase forms a double bond
, to the thioester and in the cis configuration This is followed by three rounds of the
normal elongation reactions to form palmitoleoyl-ACP Elongation may terminate at this
point or may be followed by additional biosynthetic events The principal unsaturated
fatty acid in E coli, cis-vaccenic acid, is formed by an additional elongation step, using
palmitoleoyl-ACP as a substrate
Unsaturation Reactions Occur in Eukaryotes in the Middle
of an Aliphatic Chain
The addition of double bonds to fatty acids in eukaryotes does not occur until the fatty acyl chain has reached its full length (usually 16 to 18 carbons) Dehydro-genation of stearoyl-CoA occurs in the middle of the chain, despite the absence of any useful functional group on the chain to facilitate activation:
CH3O(CH2)16COOSCoA ⎯⎯→ CH3O(CH2)7CHPCH(CH2)7COOSCoA
This impressive reaction is catalyzed by stearoyl-CoA desaturase, a 53-kD enzyme
containing a nonheme iron center NADH and O2are required, as are two other
proteins: cytochrome b5 reductase (a 43-kD flavoprotein) and cytochrome b5
(16.7 kD) All three proteins are associated with the ER membrane Cytochrome
b5 reductase transfers a pair of electrons from NADH through FAD to
cyto-chrome b5(Figure 24.14) Oxidation of reduced cytochrome b5is coupled to re-duction of nonheme Fe3to Fe2 in the desaturase The Fe3 accepts a pair of
electrons (one at a time in a cycle) from cytochrome b5and creates a cis double
bond at the 9,10-position of the stearoyl-CoA substrate O2is the terminal elec-tron acceptor in this fatty acyl desaturation cycle Note that two water molecules are made, which means that four electrons are transferred overall Two of these come through the reaction sequence from NADH, and two come from the fatty acyl substrate that is being dehydrogenated
The Unsaturation Reaction May Be Followed by Chain Elongation
Additional chain elongation can occur following this single desaturation reac-tion The oleoyl-CoA produced can be elongated by two carbons to form a 20⬊1
cis -11 fatty acyl-CoA If the starting fatty acid is palmitate, reactions similar to the preceding scheme yield palmitoleoyl-CoA (16⬊1 cis -9), which subsequently
can be elongated to yield cis -vaccenic acid (18⬊1 cis -11) Similarly, C16 and C18
fatty acids can be elongated to yield C22 and C24 fatty acids, such as are often found in sphingolipids
CH3(CH2)5 CH2 C
H
OH
CH2 C
O S-ACP
CH3(CH2)5HC
O S-ACP
H C
H2O
Acetyl-ACP+ 4 Malonyl-ACP
Four rounds of fatty acyl synthase
-Hydroxydecanoyl–ACP
-Hydroxydecanoyl
thioester dehydrase
Three rounds of fatty acyl synthase
Palmitoleoyl-ACP
(16:1 Δ9–ACP)
cis-Vaccenoyl-ACP
18:1 Δ11–ACP Elongation at ER
FIGURE 24.13 Double bonds are introduced into the
growing fatty acid chain in E coli by specific dehydrases.
Palmitoleoyl-ACP is synthesized by a sequence of
reac-tions involving four rounds of chain elongation,
fol-lowed by double bond insertion by -hydroxydecanoyl
thioester dehydrase and three additional elongation
steps Another elongation cycle produces cis-vaccenic
acid.
CH3 (CH2)7 C (CH2)7C S
H C H
CH3 (CH2)16 C
O
O
S CoA
CoA
Cytochrome b5
reductase (FAD)
2 Cytochrome b5
(Fe 3 +) (Oxidized)
H+
2 H +
2 H +
O2
2 H2O
+
Cytochrome b5
reductase (FADH 2 )
2 Cytochrome b5
(Fe 2 +) (Reduced) Desaturase(Fe 3 +)
Desaturase
(Fe2+)
+
Oleoyl-CoA
+
NAD+
NADH
FIGURE 24.14 The conversion of stearoyl-CoA to oleoyl-CoA in eukaryotes is catalyzed by stearoyl-CoA
desat-urase in a reaction sequence that also involves cytochrome b5and cytochrome b5 reductase Two electrons are passed from NADH through the chain of reactions as shown, and two electrons are derived from the fatty acyl substrate.
Trang 3Mammals Cannot Synthesize Most Polyunsaturated Fatty Acids
Organisms differ with respect to formation, processing, and utilization of
polyun-saturated fatty acids E coli, for example, does not have any polyunpolyun-saturated fatty
acids Eukaryotes do synthesize a variety of polyunsaturated fatty acids, certain
or-ganisms more than others For example, plants manufacture double bonds
be-tween the 9and the methyl end of the chain, but mammals cannot Plants
read-ily desaturate oleic acid at the 12-position (to give linoleic acid) or at both the
12- and 15-positions (producing linolenic acid) Mammals require
polyunsatu-rated fatty acids but must acquire them in their diet As such, these fatty acids are
referred to as essential fatty acids On the other hand, mammals can introduce
double bonds between the double bond at the 8- or 9-position and the carboxyl
group Enzyme complexes in the ER desaturate the 5-position, provided a double
bond exists at the 8-position, and form a double bond at the 6-position if one
al-ready exists at the 9-position Thus, oleate can be unsaturated at the 6,7-position
to give an 18⬊2 cis -6,9fatty acid
Arachidonic Acid Is Synthesized from Linoleic Acid by Mammals
Mammals can add additional double bonds to unsaturated fatty acids in their diets
Their ability to make arachidonic acid from linoleic acid is one example (Figure
24.15) This fatty acid is the precursor for prostaglandins and other biologically
ac-tive derivaac-tives such as leukotrienes Synthesis involves formation of a linoleoyl
es-ter of CoA from dietary linoleic acid, followed by introduction of a double bond at
the 6-position The triply unsaturated product is then elongated (by malonyl-CoA
with a decarboxylation step) to yield a 20-carbon fatty acid with double bonds at the
COO–
O
C
S O 6
C
S O 8
O
O
O_
+
+ P P ATP
CoA
CoA
CoA
CoA AMP
CoA Linoleic acid (18:2 Δ9,12)
Linoleoyl-CoA (18:2 Δ9,12–CoA)
Linolenoyl-CoA (18:3 Δ6,9,12–CoA)
(20:3 Δ8,11,14–CoA)
Arachidonoyl-CoA (20:4 Δ5,8,11,14–CoA)
Arachidonic acid
Acyl-CoA synthetase
2 H
2 H
Desaturation
Desaturation
CO2
Malonyl-CoA Elongation +
CoA
H2O CoA
FIGURE 24.15 Arachidonic acid is synthesized from linoleic acid in eukaryotes This is the means by which animals synthesize fatty acids with double bonds at positions other than C-9.
Trang 4736 Chapter 24 Lipid Biosynthesis
8-, 11-, and 14-positions A second desaturation reaction at the 5-position, followed
by a reverse acyl-CoA synthetase reaction (see Chapter 23), liberates the product, a
20-carbon fatty acid with double bonds at the 5-, 8-, 11-, and 14-positions
Regulatory Control of Fatty Acid Metabolism Is an Interplay
of Allosteric Modifiers and Phosphorylation–Dephosphorylation Cycles
The control and regulation of fatty acid synthesis is intimately related to regulation
of fatty acid breakdown, glycolysis, and the TCA cycle Acetyl-CoA is an important intermediate metabolite in all these processes In these terms, it is easy to appreci-ate the interlocking relationships in Figure 24.16 Malonyl-CoA can act to prevent fatty acyl-CoA derivatives from entering the mitochondria by inhibiting the carni-tine acyltransferase of the outer mitochondrial membrane that initiates this trans-port In this way, when fatty acid synthesis is turned on (as signaled by higher lev-els of malonyl-CoA), -oxidation is inhibited As we pointed out earlier, citrate is
an important allosteric activator of acetyl-CoA carboxylase, and fatty acyl-CoAs are inhibitors The degree of inhibition is proportional to the chain length of the fatty acyl-CoA; longer chains show a higher affinity for the allosteric inhibition site on acetyl-CoA carboxylase Palmitoyl-CoA, stearoyl-CoA, and arachidyl-CoA are the most potent inhibitors of the carboxylase
HUMAN BIOCHEMISTRY
3 and 6—Essential Fatty Acids with Many Functions
Linoleic acid and -linolenic acid are termed essential fatty acids
be-cause animals cannot synthesize them and must acquire them in
their diet Linoleic acid is the precursor of arachidonic acid, and
both of these are referred to as 6 fatty acids because, counting
from the end (omega, ) carbon of the chain, the first double
bond is at the sixth position (see figure) Similarly, -linolenic acid
is the precursor of eicosapentaenoic acid and docosahexaenoic
acid (DHA),and these three are termed 3 fatty acids Vegetable
oils are rich in linoleic acid and thus satisfy the body’s 6 dietary
requirements, whereas fish oils (for example, cod, herring,
men-haden, and salmon) are rich in 3 fatty acids.
Theω6 fatty acids are precursors of prostaglandins,
thrombox-anes, and leukotrienes (see Section 24.3) The 3 fatty acids have
beneficial effects in a variety of organs and biological processes, in-cluding growth regulation, platelet activation, and lipoprotein metabolism The 3 fats are generally cardioprotective,
anti-inflammatory, and anticarcinogenic
Interestingly, especially high levels of DHA have been found in rod cell membranes in animal retina and in neural tissue DHA is approximately 22% of total fatty acids in animal retina and 35% to 40% of the fatty acids in retinal phosphatidylethanolamine DHA supports neural and visual development, in part because it is a pre-cursor for eicosanoids that regulate numerous cell and organ func-tions Infants can synthesize DHA and other polyunsaturated fatty acids, but the rates of synthesis are low Strong evidence exists for the importance of these fatty acids in infant nutrition
COOH
COOH
COOH
6 Essential fatty acid
3 Essential fatty acid
COOH
COOH
Linoleic acid (18:26)
-Linoleic acid (18:3 3)
Arachidonic acid (20:4 6)
Eicosapentaenoic acid (EPA; 20:5 3)
Docosahexaenoic acid (DHA; 22:6 3)
䊳 The “” numbering system, where the position of the
first double bond relative to the methyl () group is
indi-cated (red box), is useful because the double bond
posi-tion is retained during chain elongaposi-tion and desaturaposi-tion.
Trang 5Hormonal Signals Regulate ACC and Fatty Acid Biosynthesis
As described earlier, citrate activation and palmitoyl-CoA inhibition of acetyl-CoA
carboxylase are strongly dependent on the phosphorylation state of the enzyme
This provides a crucial connection to hormonal regulation Many of the enzymes
that act to phosphorylate acetyl-CoA carboxylase (see Figure 24.4) are controlled by
hormonal signals Glucagon is a good example (Figure 24.17) As noted in Chapter
22, glucagon binding to membrane receptors activates an intracellular cascade
in-volving activation of adenylyl cyclase Cyclic AMP produced by the cyclase activates
a protein kinase, which then phosphorylates acetyl-CoA carboxylase Unless citrate
levels are high, phosphorylation causes inhibition of fatty acid biosynthesis The
car-boxylase (and fatty acid synthesis) can be reactivated by a specific phosphatase,
which dephosphorylates the carboxylase Also indicated in Figure 24.17 is the
simultaneous activation by glucagon of triacylglycerol lipases, which hydrolyze
tri-acylglycerols, releasing fatty acids for -oxidation Both the inactivation of
acetyl-CoA carboxylase and the activation of triacylglycerol lipase are counteracted by
insulin, whose receptor acts to stimulate a phosphodiesterase that converts cAMP
to AMP
Complex lipids consist of backbone structures to which fatty acids are covalently
bound Principal classes include the glycerolipids, for which glycerol is the
back-bone, and sphingolipids, which are built on a sphingosine backbone The two
major classes of glycerolipids are glycerophospholipids and triacylglycerols The
phospholipids,which include both glycerophospholipids and sphingomyelins, are
crucial components of membrane structure They are also precursors of hormones
such as the eicosanoids (for example, prostaglandins) and signal molecules (such as
the breakdown products of phosphatidylinositol ).
Different organisms possess greatly different complements of lipids and therefore
invoke somewhat different lipid biosynthetic pathways For example, sphingolipids
+
Acetyl-CoA
Citric acid cycle
Oxaloacetate
Fatty acyl-CoA
-Oxidation
Citrate
Acetyl-CoA
Malonyl-CoA
Acetyl-CoA carboxylase
Fatty acyl-CoA Fatty acid
Triacylglycerol
Carnitine
Carnitine acyltransferase-1
Citrate
Glucose
2 Pyruvate
FIGURE 24.16 Regulation of fatty acid synthesis and fatty acid oxidation are coupled as shown Malonyl-CoA, produced during fatty acid synthesis, inhibits the uptake
of fatty acylcarnitine (and thus fatty acid oxidation) by mitochondria When fatty acyl-CoA levels rise, fatty acid synthesis is inhibited and fatty acid oxidation activity increases Rising citrate levels (which reflect an abun-dance of acetyl-CoA) similarly signal the initiation of fatty acid synthesis.
Trang 6738 Chapter 24 Lipid Biosynthesis
and triacylglycerols are produced only in eukaryotes In contrast, bacteria usually have rather simple lipid compositions Phosphatidylethanolamine accounts for
at least 75% of the phospholipids in E coli, with phosphatidylglycerol and cardi-olipin accounting for most of the rest E coli membranes possess no
phosphatidyl-choline, phosphatidylinositol, sphingolipids, or cholesterol On the other hand,
some bacteria (such as Pseudomonas) can synthesize phosphatidylcholine, for
exam-ple In this section and the one following, we consider some of the pathways for the synthesis of glycerolipids, sphingolipids, and the eicosanoids, which are derived from phospholipids
Glycerolipids Are Synthesized by Phosphorylation and Acylation
of Glycerol
A common pathway operates in nearly all organisms for the synthesis of
phospha-tidic acid, the precursor to other glycerolipids Glycerokinase catalyzes the
phos-phorylation of glycerol to form glycerol-3-phosphate, which is then acylated at both the 1- and 2-positions to yield phosphatidic acid (Figure 24.18) The first acylation,
at position 1, is catalyzed by glycerol-3-phosphate acyltransferase, an enzyme that in
most organisms is specific for saturated fatty acyl groups Eukaryotic systems can
also utilize dihydroxyacetone phosphate as a starting point for synthesis of
phos-phatidic acid (Figure 24.18) Again a specific acyltransferase adds the first acyl chain,
followed by reduction of the backbone keto group by acyldihydroxyacetone phosphate
Glucagon receptor Adenylylcyclase
Insulin receptor
Dephospho-acetyl-CoA carboxylase (Active at low [citrate])
Phosphatases
Phospho-acetyl-CoA carboxylase (Active only at high [citrate])
P
cAMP
Phosphodiesterase
Glucagon
G protein
Insulin
Protein kinase
(inactive)
Protein kinase
(active)
Triacylglycerol lipase (active)
Triacylglycerol lipase (inactive)
Triacylglycerols
Fatty acids and glycerol
HPO4_
Phosphatases
HPO4_
ATP ATP
ADP
ATP
ADP AMP
FIGURE 24.17 Hormonal signals regulate fatty acid
syn-thesis, primarily through actions on acetyl-CoA
carboxy-lase Availability of fatty acids also depends upon
hor-monal activation of triacylglycerol lipase.
Trang 7reductase,using NADPH as the reductant Alternatively, dihydroxyacetone phosphate
can be reduced to glycerol-3-phosphate by glycerol-3-phosphate dehydrogenase.
Eukaryotes Synthesize Glycerolipids from CDP-Diacylglycerol
or Diacylglycerol
In eukaryotes, phosphatidic acid is converted directly either to diacylglycerol or to
cytidine diphosphodiacylglycerol (or simply CDP-diacylglycerol; Figure 24.19) From these
two precursors, all other glycerophospholipids in eukaryotes are derived
Diacylglyc-erol is a precursor for synthesis of triacylglycDiacylglyc-erol, phosphatidylethanolamine, and
C
C
CH2
CH2OH
O–
O P O–
O
O
H
Glycerol-3-P Glycerol
O S-ACP
CoA or ACP HO
C
CH2OH
CH2OH
H HO
C
CH2
CH2
O–
O P O–
O
H HO
O C
O
R1
C
O
R1
C
O
O
C
CH2
CH2
O–
O P O–
O
H O
O
C
O
R2
CoASH or ACP-SH
C
C
CH2
CH2OH
O–
O P O–
O
O O
R1
CH2
CH2
O–
O P O–
O
O
C
O
R1
+
NADH
SCoA
SCoA
CoA
ATP
ADP
R2
or
1-Acylglycerol-3-P
Glycerol-3-P acyltransferase
Glycerol-3-P dehydrogenase
1-Acylglycerol-3-P acyltransferase
Phosphatidic acid
Glycerokinase
Dihydroxyacetone-P
1-Acyldihydroxyacetone-P
Dihydroxyacetone-P
acyltransferase
Acyldihydroxyacetone-P reductase
FIGURE 24.18 Synthesis of glycerolipids in eukaryotes begins with the formation of phosphatidic
acid, which may be formed from dihydroxyacetone phosphate or glycerol as shown.
Trang 8740 Chapter 24 Lipid Biosynthesis
phosphatidylcholine Triacylglycerol is synthesized mainly in adipose tissue, liver, and intestines and serves as the principal energy storage molecule in eukaryotes
Triacyl-glycerol biosynthesis in liver and adipose tissue occurs via diacylTriacyl-glycerol
acyltrans-ferase,an enzyme bound to the cytoplasmic face of the ER A different route is used, however, in intestines Recall (see Figure 23.3) that triacylglycerols from the diet are
CH2
HOCH2CH2NH3
OCH2CH2NH3 –O
P
O –O
+
+
OCH2CH2NH3 O–
P
O O
+ P
O–
O
O Cytidine
OCH2CH2NH3 O–
P
O O
+ O
C
O
R2
CH2 O C
O
R1
CH2OH
O C O
R2
CH2 O C
O
R1
Diacylglycerol
C
O
C H O C O
R2
CH2 O C
O
R1
O
R3
O C O
R2
CH2 O C
O
R1
CH2 O OCH2CH2N(CH3)3
O–
P
O
+
O–
P
O O P O–
O O Cytidine
OCH2CH2N(CH+ 3)3
–O P
O –O OCH2CH2N(CH+ 3)3 HOCH2CH2N(CH+ 3)3
Phosphatidic acid
CH2
O C O
R2
CH2 O C
O
R1
O O–
P
O O–
P P
P
P P
CH
CH CH
CH
P P
CTP
CH2
R1
CH
CH2 O C O
R2
O
O–
O
O–
O
ATP
ATP ATP
Ethanolamine
Ethanolamine kinase
Phosphoethanolamine CTP:
Phospho-ethanolamine
cytidylyltransferase
CDP-ethanolamine
Phosphatidylethanolamine
CoASH
Diacylglycerol acyltransferase
Triacylglycerol
Phosphatidylcholine
CDP-ethanolamine:
1,2-diacylglycerol
phospho-ethanolamine transferase
CMP
CDP-choline
CDP-choline:
1,2-diacylgly-cerol phospho-choline transferase
Choline
Choline kinase
Phosphocholine
CTP: Phosphocholine cytidylyltransferase
Phosphatidic acid phosphatase
Diacylglycerol kinase
CTP
CTP
CMP
Phosphatidate cytidylyltransferase
CDP-diacylglycerol
ADP ADP
FIGURE 24.19 Diacylglycerol and CDP-diacylglycerol are the principal precursors of glycerolipids in eukaryotes Phosphatidylethanolamine and phosphatidylcholine are formed by reaction of diacylglycerol with CDP-ethanolamine or CDP-choline, respectively.
Trang 9broken down to 2-monoacylglycerols by specific lipases Acyltransferases then acylate
2-monoacylglycerol to produce new triacylglycerols (Figure 24.20)
Phosphatidylethanolamine Is Synthesized from Diacylglycerol
and CDP-Ethanolamine
Phosphatidylethanolamine synthesis begins with phosphorylation of ethanolamine
to form phosphoethanolamine (see Figure 24.19) The next reaction involves
trans-fer of a cytidylyl group from CTP to form CDP-ethanolamine and pyrophosphate As
always, PPihydrolysis drives this reaction forward A specific phosphoethanolamine
transferasethen links phosphoethanolamine to the diacylglycerol backbone
Bio-synthesis of phosphatidylcholine is entirely analogous because animals can
synthe-size it directly All of the choline utilized in this pathway must be acquired from the
diet On the other hand, yeast, certain bacteria, and animal livers can convert
phosphatidylethanolamine to phosphatidylcholine by methylation reactions
involv-ing S -adenosylmethionine (see Chapter 25).
Exchange of Ethanolamine for Serine Converts
Phosphatidylethanolamine to Phosphatidylserine
Mammals synthesize phosphatidylserine (PS) in a calcium ion–dependent reaction
involving aminoalcohol exchange (Figure 24.21) The enzyme catalyzing this reaction
is associated with the ER and will accept phosphatidylethanolamine (PE) and other
phospholipid substrates A mitochondrial PS decarboxylase can subsequently convert
PS to PE No other pathway converting serine to ethanolamine has been found
Eukaryotes Synthesize Other Phospholipids Via CDP-Diacylglycerol
Eukaryotes also use CDP-diacylglycerol, derived from phosphatidic acid, as a
precur-sor for several other important phospholipids, including phosphatidylinositol (PI),
phosphatidylglycerol (PG), and cardiolipin (Figure 24.22) PI accounts for only about
O C
O
CH2OH
CH2OH
C
O
CH
CH2
CH2OH
O C
O
R1
C
R3 O
C
O
R2
C
O
R2
CH
CH2 O
O
O C
O
R1
CH2 O C
O
R3
H
SCoA
CoA
2-Monoacylglycerol
Monoacylglycerol acyltransferase
Diacylglycerol
Diacylglycerol acyltransferase
Triacylglycerol
Lipases
Dietary triacylglycerols
CoASH
CoASH
FIGURE 24.20 Triacylglycerols are formed primarily by the action of acyltransferases on monoacylglycerol and diacylglycerol.
O
CH2
CH O C O
R2
CH2 O C
O
R1
O O–
O–
P
O
CH2 CH2 NH+ 3
O
CH2
CH O C O
R2
CH2 O C
O
R1
O
CH2 C H
COO–
NH+ 3
Phosphatidylethanolamine
Serine Serine
CO2
Ethanolamine Ethanolamine
Base exchange enzyme (endoplasmic reticulum)
Phosphatidylserine
decarboxylase
(mitochondria)
Phosphatidylserine
Serine
FIGURE 24.21 The interconversion of phosphatidylethanolamine and phosphatidylserine in mammals.
Trang 10742 Chapter 24 Lipid Biosynthesis
CH2
CH2
O P O–
O
C
O
O P O–
O CH2
O
OH OH
N
NH2
CH2
O
CH2 OH
CH2
O P O C
O–
O–
CH2
O P O–
O
O
O
O P O–
CH2 C OH
CH2OH H
Glycerol
CDP-diacylglycerol
CH2
O P O–
O
O
OH
CH2
P O–
O
O
O O
CH2 C
O
CH2
O
O
O OH
OH OH
H
H H
H
OH HO
CH2 C
O
CH2 C
O
C
O
H
H H
CDP-diacylglycerol
CMP CMP
Glycerol-3-P Inositol
Glycerophosphate phosphatidyltransferase Phosphatidylinositol synthase
Phosphoglycerol
Phosphatidylglycerol-P
Pi
Phosphatidylinositol
Phosphatidylglycerol-P phosphatase
Phosphatidylglycerol
CMP
Cardiolipin synthase
Glycerol
Cardiolipin
R1
R2
FIGURE 24.22 CDP-diacylglycerol is a precursor of phosphatidylinositol, phosphatidylglycerol, and cardiolipin in eukaryotes.