第 28章
脂类物质的分解
与合成代谢
? 脂类主要包括甘油三酯（脂肪）、磷脂和类固醇等。
脂类代谢是指在生物细胞内上述各类物质的生物合
成和分解过程。脂类代谢对于生命活动具有重要意
义。
? （ 1）脂肪在动物体内和植物种子及果实中大量存
储。脂肪在氧化时可以比其他能源物质提供更多的
能量。每克脂肪氧化时可释放出 38.9 kJ 的能量，
每克糖和蛋白质氧化时释放的能量仅分别为 17.2
kJ和 23.4 kJ。
? （ 2） 许多类脂及其衍生物具有重要生理作用。脂
类代谢的中间产物是合成激素、胆酸和维生素等的
基本原料，对维持机体的正常活动有重要影响作用。
? （ 3）人类的某些疾病如动脉粥样硬化、脂肪肝和
酮尿症等都与脂类代谢紊乱有关。
一、脂肪消化、吸收与分解代谢
? 脂肪的消化和吸收主要在 小肠中 进行。
? 脂肪在脂肪酶催化下水解成甘油和脂肪
酸，它们在生物体内将沿着不同途径进
行代谢。
? 胰脂肪酶是一种非专一性水解酶，对脂
肪酸碳链的长短及饱和度专一性不严格。
但该酶具有较好的位置选择性，即易于
水解甘油酯的 1位及 3位的酯键，主要产
物为甘油单酯和脂肪酸。甘油单酯则被
另一种甘油单酯脂肪酶水解，得到甘油
和脂肪酸。
1．甘油的代谢
? 甘油经血液输送到肝脏后，
在 ATP存在下，由甘油激酶
催化，转变成 ?-磷酸甘油。
这是一个不可逆反应过程。
?-磷酸甘油在脱氢酶（含辅
酶 NAD+） 作用下，脱氢形成
磷酸二羟丙酮。磷酸二羟丙
酮是糖酵解途径的一个中间
产物，它可以沿着糖酵解途
径的逆过程合成葡萄糖及糖
原；也可以沿着糖酵解正常
途径形成丙酮酸，再进入三
羧酸循环被完全氧化。
2．脂肪酸的分解代谢
?（ 1）脂肪酸的 ?-氧化
?Early labeling experiments revealed that
fatty acids are degraded by sequential
removal of two-carbon units,
Franz Knoop’s labeling
experiments (1904),
fatty acids are degraded
by oxidation at the ?
carbon,or ?- oxidation,
?
?
?
?
dogs fed with
odd-numbered
fatty acids
attached to a
phenyl group
benzoate was
excreted
even-numbered
phenylacetate
synthetic label
?脂肪酸的 ?-氧化作用是指脂肪酸在
氧化分解时，碳链的断裂发生在脂
肪酸的 ?-位，即脂肪酸碳链的断裂
方式是每次切除 2个碳原子。脂肪酸
的 ?-氧化是含偶数碳原子或奇数碳
原子脂肪酸的主要分解方式。
?脂肪酸的 ?-氧化在线粒体中进行。
? 脂肪酸的活化
? 脂肪酸进入细胞后，首先在线粒体外
或胞浆中被活化，形成脂酰 CoA,然后
进入线粒体进行氧化。
? 在脂酰 CoA合成酶催化下，由 ATP提供
能量，将脂肪酸转变成 脂酰 CoA,
? 脂酰 CoA转运入线粒体
? 催化脂酰 CoA氧化分解的酶存在于线粒体的
基质中，所以脂酰 CoA必须通过线粒体内膜
进入基质中才能进行氧化分解。
? 脂酰 CoA需要借助一种特殊的 载体肉毒碱 (3-
羟基 -4-三甲氨基丁酸 )才能转运到线粒体内。
脂酰 CoA在肉毒碱脂酰转移酶催化下，与肉
毒碱反应，生长脂酰肉毒碱，然后通过线粒
体内膜。脂酰肉毒碱在线粒体内膜的移位酶
帮助下穿过内膜，并与线粒体基质中的 CoA
作用，重新生成脂酰 CoA,释放出肉毒碱。
肉毒碱再在移位酶帮助下，回到线粒体外的
细胞质中。
(2)
软
脂
酸
的
?-
氧
化
步
骤
（ 3） 脂肪酸氧化与 ATP
合成
? 与葡萄糖的氧化分解相似，
脂肪酸的氧化分解也由三
个阶段组成,
? 第一阶段,脂肪酸的 ?-氧
化；
? 第二阶段,产生的乙酰辅
酶 A进入三羧酸循环彻底
氧化。
? 第三阶段,前两个阶段产
生的还原性辅酶进入呼吸
链，经电子传递，最终将
氢和电子交给分子氧生产
水，释放出的能量合成
ATP。
Yield of ATP during oxidation of one molecule of palmitoyl-CoA to CO2
and H2O
Enzyme catalyzing
oxidation step
NADH or FADH2
formed
Number of ATP ultimately
formed
Acyl-CoA dehydrogenase 7 FADH2 10.5
β-Hydroxyacyl-CoA
dehydrogenase 7 NADH 17.5
Isocitrate dehydrogenase 8 NADH 20
α-Ketoglutarate
dehydrogenase 8 NADH 20
Succinyl-CoA synthetase 8*
Succinate dehydrogenase 8 FADH2 12
Malate dehydrogenase 8 NADH 20
Total 108
3,不饱和脂肪酸的分解代谢
?Oxidation of unsaturated fatty
acids requires one or two
auxiliary enzymes,an
isomerase and a reductase
Odd-position single double bond
Enoyl-CoA
isomerase cis-?3 is converted to trans-?2
Odd-numbered double
bonds are handled by
the isomerase,
2,4-dienoyl-CoA
Reductase A trans-?2,cis-?4 structure is converted
to a trans-?3 structure (consuming NADPH)
亚油酰 -CoA
Even-numbered double bonds are
handled by the reductase and the
isomerase,
4,奇数碳原子脂肪酸的氧化
?首先经过数次 ?-氧化,最后剩下一
个 丙酰 CoA,
?Propionyl-CoA ( three amino acids)
is converted to succinyl-CoA
Convertion of Propionyl-CoA to
succinyl-CoA
The carboxyl that is in ester linkage to the thiol of
coenzyme A is shifted from one carbon atom to another,
with opposite shift of a hydrogen atom
5,酮体的生成与
利用
（ 1） Excess acetyl-
CoA in liver can be
exported as ketone
bodies
(2) Ketone bodies are
converted back to acetyl-
CoA in extrahepatic
tissues
? Heart muscle and the renal cortex
use acetoacetate (as a normal
fuel of respiration) in preference
to glucose even under normal
conditions,
? The brain adapts to the utilization
of acetoacetate during starvation
and diabetes (accounts for ~75%
of the energy needs),
二、脂肪酸的生物合成
1,脂肪酸合成与分解的途径不同
?Occurs in the cytosol (chloroplasts in
plants),
?Acetyl-CoA provides the first two carbons,
which is elongated by sequential addition
of two-carbon units donated from malonyl-
CoA,
?Intermediates are attached to the -SH
groups of an acyl carrier protein (ACP),
?NADPH is the reductant,
?The enzymes are associated as a multi-
enzyme complex or even being in one
polypeptide chain in higher organisms
(fatty acid synthase),
?Elongation by the fatty acid synthase
complex stops upon formation of palmitate
(C16),further elongation and desaturation
are carried out by other enzyme systems,
2,Malonyl-CoA is formed from
acetyl-CoA
?Salih Wakil discovered that HCO3-
is required for fatty acid synthesis,
?Acetyl-CoA carboxylase (being
trimeric in bacteria,monomeric in
animals and both in plants)
catalyzes this carboxylation
reaction,
?The enzyme has three functional parts,a
biotin carrier protein; an ATP-dependent
biotin carboxylase; and a transcarboxylase,
?The enzyme exemplifies a ping-pong
reaction mechanism,
?This irreversible reaction commits acetyl-
CoA to fatty acid synthesis,
biotin
carboxylase
Trans-
carboxylase
Acetyl-CoA carboxylase
catalyzes the two-step
carboxylation reaction
of acetyl-CoA in two
active sites,
3,The acetyl and malony groups are first
transferred to two –SH groups of the fatty
acid synthase complex
?The acetyl group of acetyl-CoA is first transferred to
the –SH group of a Cys residue on the ?-ketoacyl-ACP
synthase (KS) in a reaction catalyzed by acetyl-CoA-
ACP transacetylase (AT),
?The malonyl group is transferred from malonyl-CoA to
the –SH group of the 4`-phosphopantetheine
covalently attached to a Ser residue of the acyl carrier
protein (ACP),
4,Fatty acids are synthesized by a
repeating four-step reaction sequence
?In the condensation reaction (step 1),catalyzed by ?-
ketoacyl-ACP synthase,the methylene group of
malonyl-CoA (linked to ACP) undergoes a nucleophilic
attack on the carbonyl carbon of the acetyl group
linked to KS,forming the ?-ketobutyryl-ACP with
simultaneous elimination of CO2,
?the ?-ketobutyryl-ACP is then reduced to D-?-
hydroxybutyryl-ACP (step 2),using NADPH and the ?-
ketobutyryl-ACP reductase (KR),
?A water molecule is then removed from the ?-
hydroxybutyryl-ACP to produce trans-?2-butenoyl-
ACP in a reaction catalyzed by ?-hydroxybutyryl-ACP
dehydratase (step 3),
? A further reduction (step 4),also using NADPH,of
the carbon-carbon double in trans-?2-butenoyl-ACP,
catalyzed by enoyl-ACP reductase produces a
saturated acyl on ACP (butyryl-ACP),
?The butyryl group is then transferred to the Cys –SH
group of ?-ketoacyl-ACP synthase for another round
of four reactions,which will extend the chain by two
more carbons,
? AT,Acetyl-CoA-ACP
transacetylase
? MT,Malonyl-CoA-
ACP transferase
? KS,β-ketoacyl-ACP
synthase
? KR,β -ketobutyryl-
ACP reductase
? HD,β-hydroxyacyl-
ACP dehydratase
? ER,Enoyl-ACP
reductase
5,The seven activities of fatty acid synthesis from
different organisms have different level of integration
?Each activity resides in a separate
polypeptide chain in bacteria and higher
plants,
?The seven activities reside in two separate
polypeptide chains,with the synthase present
as dodecamers (?6? 6),
?The seven activities reside in one large
polypeptide chain in vertebrates,with the
synthase present as dimers,
6,Fatty acid synthesis occurs in cellular
compartments having a high NADPH/NADP+
ratio
?NAD and NADP have selected for functioning
as electron carriers in oxidative catablism and
reductive anabolism respectively,
?In the hepatocytes and adipocytes,NADPH is
mainly produced in the cytosol via the pentose
phosphate pathway and by the malic enzyme,
?In photosynthetic plants,fatty acid synthesis
occur in the chloroplast stroma,using NADPH
made from photophosphorylation,
7,The acetyl groups of the mitochondrion
are transported into the cytosol in the form
of citrate
?The acetyl-CoA molecules are made from
glucose and amino acids in mitochondria,
?The are shuttled into the cytosol in the form of
citrate via the citrate transporter of the inner
membrane,
?Acetyl-CoA is regenerated by the action of ATP-
dependent citrate lyase in the cytosol,
8,The rate of fatty acid biosynthesis is
controlled by acetyl-CoA carboxylase
?Excess fuel is generally converted to fatty
acids/triacylglycerol for longer term storage,
?Acetyl-CoA carboxylase,catalyzing the committing
and rate-limiting step of fatty acid synthesis,is
allosterically inhibited by palmitoyl-CoA and activated
by citrate,
?Glucagon and epinephrine triggers the
phosphorylation and disassociation of the polymeric
enzyme subunits,which inactivates the enzyme,
?Citrate partially activate the
phosphorylated acetyl-CoA carboxylase
(similar to how AMP partially active the
dephosphorylated glycogen
phosphorylase),
?In plants,acetyl-CoA carboxylase is
activated by a increase of Mg 2+
concentration and decrease of H+
concentration that accompany illumination,
9,Palmitate can be further elongated and
desaturated in smooth ER
?Palmitoyl-CoA can be further elongated by the
fatty acid elongation system present mainly in
the smooth endoplasmic reticulum,with two-
carbon units also donated by malonyl-CoA,
?Palmitoyl-CoA and Stearoyl-CoA can be
desaturated between C-9 and C-10 to produce
palmitoleate,16:1( ?9),and oleate,18:1( ?9)
respectively,
?The double bonds are introduced by the catalysis of
fatty acyl-CoA desaturase (a mixed-function
oxidase),where both the fatty acyl group and
NADPH are oxidized by O2,
?The electrons of NADPH are transferred to O2 via
Cyt b5 reductase and cytochrome b5,
?Further desaturation of oleate occur on
phosphatidylcholine and is catalyzed by another
desaturase,which is present only in plant cells,
?Linoleate and linolenate,needed to make other
polyunsaturated fatty acids like arachidonate are
essential fatty acids for mammals,
三、磷脂的代谢
CH
2
C-R
1
O
O
CHR
2
-C
O
O
CH
2
P
O
O
OO X
P h os ph ol i pa s e A
P h os ph ol i pa s e B
P h os ph ol i pa s e C
P h os ph ol i pa s e D
1,
磷
脂
的
水
解
2,磷脂的生物合成
?Phosphatidic acid is the common
precursor for the syntheses of both
triacylglycerols and
glycerophospholipids
?Two strategies are taken for
converting phosphatidic acid to
glycerophospholipid
四、固醇类的生物合成
The process occurs in four stages,
? Stage 1,the three acetate units condense
to form a six-carbon intermediate,
mevalonate,
? Stage 2,involves the conversion of
mevalonate into activated isoprene units,
? Stage 3,the polymerization of six 5-
carbon isoprene units ta form the 30-
carbon linear structure of squalene,
? Stage 4,the cyclization of squalene forms
the four rings of the steroid nucleus,and a
further series of changes leads to the final
product,cholesterol,
Thanks!
Emulsification,digestion,absorption
and transport of diet triacylglycerol Bile salts
Emulsification
& digestion
absorption
Pancreatic lipases
脂酰辅酶 A的合成
脂酰基的转运
Structure of
coenzyme B12
3-D structure of coenzyme B12
and penicillin,
Malic
enzyme
Pentose phosphate
pathway
NADPH in the cytosol of animal cells
is largely produced by the oxidative
decarboxylation of malate and the
pentose phosphate pathway
Dephosphorylated
acetyl-CoA
Carboxylase
(active)
Acetyl-CoA carboxylase
is regulated by allosteric
effectors and reversible
phosphorylation
Citrate partially activate the phosphorylated
acetyl-CoA carboxylase
Bacteria mainly use
this strategy
Eukaryotic cells
use both strategies
(occurring on sER and
inner membrane of
mitochondria)
The "salvage" pathway
from phosphatidylserine to
phosphatidylethanolamine
and phosphatidylcholine in
yeast,Phosphatidylserine
and
phosphatidylethanolamine
are interconverted by a
reversible head group
exchange reaction,
The pathway for
phosphatidylcholine
synthesis from choline in
mammals,The same
strategy is used for
salvaging ethanolamine in
phosphatidylethanolamine
synthesis,
Formation of mevalonate
from acetyl-CoA,The
origin of C-1 and C-2 of
mevalonate from acetyl-
CoA is shown in red,
脂类物质的分解
与合成代谢
? 脂类主要包括甘油三酯（脂肪）、磷脂和类固醇等。
脂类代谢是指在生物细胞内上述各类物质的生物合
成和分解过程。脂类代谢对于生命活动具有重要意
义。
? （ 1）脂肪在动物体内和植物种子及果实中大量存
储。脂肪在氧化时可以比其他能源物质提供更多的
能量。每克脂肪氧化时可释放出 38.9 kJ 的能量，
每克糖和蛋白质氧化时释放的能量仅分别为 17.2
kJ和 23.4 kJ。
? （ 2） 许多类脂及其衍生物具有重要生理作用。脂
类代谢的中间产物是合成激素、胆酸和维生素等的
基本原料，对维持机体的正常活动有重要影响作用。
? （ 3）人类的某些疾病如动脉粥样硬化、脂肪肝和
酮尿症等都与脂类代谢紊乱有关。
一、脂肪消化、吸收与分解代谢
? 脂肪的消化和吸收主要在 小肠中 进行。
? 脂肪在脂肪酶催化下水解成甘油和脂肪
酸，它们在生物体内将沿着不同途径进
行代谢。
? 胰脂肪酶是一种非专一性水解酶，对脂
肪酸碳链的长短及饱和度专一性不严格。
但该酶具有较好的位置选择性，即易于
水解甘油酯的 1位及 3位的酯键，主要产
物为甘油单酯和脂肪酸。甘油单酯则被
另一种甘油单酯脂肪酶水解，得到甘油
和脂肪酸。
1．甘油的代谢
? 甘油经血液输送到肝脏后，
在 ATP存在下，由甘油激酶
催化，转变成 ?-磷酸甘油。
这是一个不可逆反应过程。
?-磷酸甘油在脱氢酶（含辅
酶 NAD+） 作用下，脱氢形成
磷酸二羟丙酮。磷酸二羟丙
酮是糖酵解途径的一个中间
产物，它可以沿着糖酵解途
径的逆过程合成葡萄糖及糖
原；也可以沿着糖酵解正常
途径形成丙酮酸，再进入三
羧酸循环被完全氧化。
2．脂肪酸的分解代谢
?（ 1）脂肪酸的 ?-氧化
?Early labeling experiments revealed that
fatty acids are degraded by sequential
removal of two-carbon units,
Franz Knoop’s labeling
experiments (1904),
fatty acids are degraded
by oxidation at the ?
carbon,or ?- oxidation,
?
?
?
?
dogs fed with
odd-numbered
fatty acids
attached to a
phenyl group
benzoate was
excreted
even-numbered
phenylacetate
synthetic label
?脂肪酸的 ?-氧化作用是指脂肪酸在
氧化分解时，碳链的断裂发生在脂
肪酸的 ?-位，即脂肪酸碳链的断裂
方式是每次切除 2个碳原子。脂肪酸
的 ?-氧化是含偶数碳原子或奇数碳
原子脂肪酸的主要分解方式。
?脂肪酸的 ?-氧化在线粒体中进行。
? 脂肪酸的活化
? 脂肪酸进入细胞后，首先在线粒体外
或胞浆中被活化，形成脂酰 CoA,然后
进入线粒体进行氧化。
? 在脂酰 CoA合成酶催化下，由 ATP提供
能量，将脂肪酸转变成 脂酰 CoA,
? 脂酰 CoA转运入线粒体
? 催化脂酰 CoA氧化分解的酶存在于线粒体的
基质中，所以脂酰 CoA必须通过线粒体内膜
进入基质中才能进行氧化分解。
? 脂酰 CoA需要借助一种特殊的 载体肉毒碱 (3-
羟基 -4-三甲氨基丁酸 )才能转运到线粒体内。
脂酰 CoA在肉毒碱脂酰转移酶催化下，与肉
毒碱反应，生长脂酰肉毒碱，然后通过线粒
体内膜。脂酰肉毒碱在线粒体内膜的移位酶
帮助下穿过内膜，并与线粒体基质中的 CoA
作用，重新生成脂酰 CoA,释放出肉毒碱。
肉毒碱再在移位酶帮助下，回到线粒体外的
细胞质中。
(2)
软
脂
酸
的
?-
氧
化
步
骤
（ 3） 脂肪酸氧化与 ATP
合成
? 与葡萄糖的氧化分解相似，
脂肪酸的氧化分解也由三
个阶段组成,
? 第一阶段,脂肪酸的 ?-氧
化；
? 第二阶段,产生的乙酰辅
酶 A进入三羧酸循环彻底
氧化。
? 第三阶段,前两个阶段产
生的还原性辅酶进入呼吸
链，经电子传递，最终将
氢和电子交给分子氧生产
水，释放出的能量合成
ATP。
Yield of ATP during oxidation of one molecule of palmitoyl-CoA to CO2
and H2O
Enzyme catalyzing
oxidation step
NADH or FADH2
formed
Number of ATP ultimately
formed
Acyl-CoA dehydrogenase 7 FADH2 10.5
β-Hydroxyacyl-CoA
dehydrogenase 7 NADH 17.5
Isocitrate dehydrogenase 8 NADH 20
α-Ketoglutarate
dehydrogenase 8 NADH 20
Succinyl-CoA synthetase 8*
Succinate dehydrogenase 8 FADH2 12
Malate dehydrogenase 8 NADH 20
Total 108
3,不饱和脂肪酸的分解代谢
?Oxidation of unsaturated fatty
acids requires one or two
auxiliary enzymes,an
isomerase and a reductase
Odd-position single double bond
Enoyl-CoA
isomerase cis-?3 is converted to trans-?2
Odd-numbered double
bonds are handled by
the isomerase,
2,4-dienoyl-CoA
Reductase A trans-?2,cis-?4 structure is converted
to a trans-?3 structure (consuming NADPH)
亚油酰 -CoA
Even-numbered double bonds are
handled by the reductase and the
isomerase,
4,奇数碳原子脂肪酸的氧化
?首先经过数次 ?-氧化,最后剩下一
个 丙酰 CoA,
?Propionyl-CoA ( three amino acids)
is converted to succinyl-CoA
Convertion of Propionyl-CoA to
succinyl-CoA
The carboxyl that is in ester linkage to the thiol of
coenzyme A is shifted from one carbon atom to another,
with opposite shift of a hydrogen atom
5,酮体的生成与
利用
（ 1） Excess acetyl-
CoA in liver can be
exported as ketone
bodies
(2) Ketone bodies are
converted back to acetyl-
CoA in extrahepatic
tissues
? Heart muscle and the renal cortex
use acetoacetate (as a normal
fuel of respiration) in preference
to glucose even under normal
conditions,
? The brain adapts to the utilization
of acetoacetate during starvation
and diabetes (accounts for ~75%
of the energy needs),
二、脂肪酸的生物合成
1,脂肪酸合成与分解的途径不同
?Occurs in the cytosol (chloroplasts in
plants),
?Acetyl-CoA provides the first two carbons,
which is elongated by sequential addition
of two-carbon units donated from malonyl-
CoA,
?Intermediates are attached to the -SH
groups of an acyl carrier protein (ACP),
?NADPH is the reductant,
?The enzymes are associated as a multi-
enzyme complex or even being in one
polypeptide chain in higher organisms
(fatty acid synthase),
?Elongation by the fatty acid synthase
complex stops upon formation of palmitate
(C16),further elongation and desaturation
are carried out by other enzyme systems,
2,Malonyl-CoA is formed from
acetyl-CoA
?Salih Wakil discovered that HCO3-
is required for fatty acid synthesis,
?Acetyl-CoA carboxylase (being
trimeric in bacteria,monomeric in
animals and both in plants)
catalyzes this carboxylation
reaction,
?The enzyme has three functional parts,a
biotin carrier protein; an ATP-dependent
biotin carboxylase; and a transcarboxylase,
?The enzyme exemplifies a ping-pong
reaction mechanism,
?This irreversible reaction commits acetyl-
CoA to fatty acid synthesis,
biotin
carboxylase
Trans-
carboxylase
Acetyl-CoA carboxylase
catalyzes the two-step
carboxylation reaction
of acetyl-CoA in two
active sites,
3,The acetyl and malony groups are first
transferred to two –SH groups of the fatty
acid synthase complex
?The acetyl group of acetyl-CoA is first transferred to
the –SH group of a Cys residue on the ?-ketoacyl-ACP
synthase (KS) in a reaction catalyzed by acetyl-CoA-
ACP transacetylase (AT),
?The malonyl group is transferred from malonyl-CoA to
the –SH group of the 4`-phosphopantetheine
covalently attached to a Ser residue of the acyl carrier
protein (ACP),
4,Fatty acids are synthesized by a
repeating four-step reaction sequence
?In the condensation reaction (step 1),catalyzed by ?-
ketoacyl-ACP synthase,the methylene group of
malonyl-CoA (linked to ACP) undergoes a nucleophilic
attack on the carbonyl carbon of the acetyl group
linked to KS,forming the ?-ketobutyryl-ACP with
simultaneous elimination of CO2,
?the ?-ketobutyryl-ACP is then reduced to D-?-
hydroxybutyryl-ACP (step 2),using NADPH and the ?-
ketobutyryl-ACP reductase (KR),
?A water molecule is then removed from the ?-
hydroxybutyryl-ACP to produce trans-?2-butenoyl-
ACP in a reaction catalyzed by ?-hydroxybutyryl-ACP
dehydratase (step 3),
? A further reduction (step 4),also using NADPH,of
the carbon-carbon double in trans-?2-butenoyl-ACP,
catalyzed by enoyl-ACP reductase produces a
saturated acyl on ACP (butyryl-ACP),
?The butyryl group is then transferred to the Cys –SH
group of ?-ketoacyl-ACP synthase for another round
of four reactions,which will extend the chain by two
more carbons,
? AT,Acetyl-CoA-ACP
transacetylase
? MT,Malonyl-CoA-
ACP transferase
? KS,β-ketoacyl-ACP
synthase
? KR,β -ketobutyryl-
ACP reductase
? HD,β-hydroxyacyl-
ACP dehydratase
? ER,Enoyl-ACP
reductase
5,The seven activities of fatty acid synthesis from
different organisms have different level of integration
?Each activity resides in a separate
polypeptide chain in bacteria and higher
plants,
?The seven activities reside in two separate
polypeptide chains,with the synthase present
as dodecamers (?6? 6),
?The seven activities reside in one large
polypeptide chain in vertebrates,with the
synthase present as dimers,
6,Fatty acid synthesis occurs in cellular
compartments having a high NADPH/NADP+
ratio
?NAD and NADP have selected for functioning
as electron carriers in oxidative catablism and
reductive anabolism respectively,
?In the hepatocytes and adipocytes,NADPH is
mainly produced in the cytosol via the pentose
phosphate pathway and by the malic enzyme,
?In photosynthetic plants,fatty acid synthesis
occur in the chloroplast stroma,using NADPH
made from photophosphorylation,
7,The acetyl groups of the mitochondrion
are transported into the cytosol in the form
of citrate
?The acetyl-CoA molecules are made from
glucose and amino acids in mitochondria,
?The are shuttled into the cytosol in the form of
citrate via the citrate transporter of the inner
membrane,
?Acetyl-CoA is regenerated by the action of ATP-
dependent citrate lyase in the cytosol,
8,The rate of fatty acid biosynthesis is
controlled by acetyl-CoA carboxylase
?Excess fuel is generally converted to fatty
acids/triacylglycerol for longer term storage,
?Acetyl-CoA carboxylase,catalyzing the committing
and rate-limiting step of fatty acid synthesis,is
allosterically inhibited by palmitoyl-CoA and activated
by citrate,
?Glucagon and epinephrine triggers the
phosphorylation and disassociation of the polymeric
enzyme subunits,which inactivates the enzyme,
?Citrate partially activate the
phosphorylated acetyl-CoA carboxylase
(similar to how AMP partially active the
dephosphorylated glycogen
phosphorylase),
?In plants,acetyl-CoA carboxylase is
activated by a increase of Mg 2+
concentration and decrease of H+
concentration that accompany illumination,
9,Palmitate can be further elongated and
desaturated in smooth ER
?Palmitoyl-CoA can be further elongated by the
fatty acid elongation system present mainly in
the smooth endoplasmic reticulum,with two-
carbon units also donated by malonyl-CoA,
?Palmitoyl-CoA and Stearoyl-CoA can be
desaturated between C-9 and C-10 to produce
palmitoleate,16:1( ?9),and oleate,18:1( ?9)
respectively,
?The double bonds are introduced by the catalysis of
fatty acyl-CoA desaturase (a mixed-function
oxidase),where both the fatty acyl group and
NADPH are oxidized by O2,
?The electrons of NADPH are transferred to O2 via
Cyt b5 reductase and cytochrome b5,
?Further desaturation of oleate occur on
phosphatidylcholine and is catalyzed by another
desaturase,which is present only in plant cells,
?Linoleate and linolenate,needed to make other
polyunsaturated fatty acids like arachidonate are
essential fatty acids for mammals,
三、磷脂的代谢
CH
2
C-R
1
O
O
CHR
2
-C
O
O
CH
2
P
O
O
OO X
P h os ph ol i pa s e A
P h os ph ol i pa s e B
P h os ph ol i pa s e C
P h os ph ol i pa s e D
1,
磷
脂
的
水
解
2,磷脂的生物合成
?Phosphatidic acid is the common
precursor for the syntheses of both
triacylglycerols and
glycerophospholipids
?Two strategies are taken for
converting phosphatidic acid to
glycerophospholipid
四、固醇类的生物合成
The process occurs in four stages,
? Stage 1,the three acetate units condense
to form a six-carbon intermediate,
mevalonate,
? Stage 2,involves the conversion of
mevalonate into activated isoprene units,
? Stage 3,the polymerization of six 5-
carbon isoprene units ta form the 30-
carbon linear structure of squalene,
? Stage 4,the cyclization of squalene forms
the four rings of the steroid nucleus,and a
further series of changes leads to the final
product,cholesterol,
Thanks!
Emulsification,digestion,absorption
and transport of diet triacylglycerol Bile salts
Emulsification
& digestion
absorption
Pancreatic lipases
脂酰辅酶 A的合成
脂酰基的转运
Structure of
coenzyme B12
3-D structure of coenzyme B12
and penicillin,
Malic
enzyme
Pentose phosphate
pathway
NADPH in the cytosol of animal cells
is largely produced by the oxidative
decarboxylation of malate and the
pentose phosphate pathway
Dephosphorylated
acetyl-CoA
Carboxylase
(active)
Acetyl-CoA carboxylase
is regulated by allosteric
effectors and reversible
phosphorylation
Citrate partially activate the phosphorylated
acetyl-CoA carboxylase
Bacteria mainly use
this strategy
Eukaryotic cells
use both strategies
(occurring on sER and
inner membrane of
mitochondria)
The "salvage" pathway
from phosphatidylserine to
phosphatidylethanolamine
and phosphatidylcholine in
yeast,Phosphatidylserine
and
phosphatidylethanolamine
are interconverted by a
reversible head group
exchange reaction,
The pathway for
phosphatidylcholine
synthesis from choline in
mammals,The same
strategy is used for
salvaging ethanolamine in
phosphatidylethanolamine
synthesis,
Formation of mevalonate
from acetyl-CoA,The
origin of C-1 and C-2 of
mevalonate from acetyl-
CoA is shown in red,
