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Chapter 21
Lipid Metabolism
生化科 吳嘉霖老師 第一醫學大樓0859室 校內分機：5159 Lipid metabolism and hibernation （冬眠）�
棕熊在冬眠6個月時會消耗掉100萬大卡的卡路里，相當於1個美國
人1年所需的熱量 Lipids are Involved in Generation and
Storage of Energy
•  The oxidation of fatty acids (FA) in triacylglycerols are the
principal storage form of energy for most organisms
•  The energy yield per gram of fatty acid oxidized is greater
than that per gram of carbohydrate oxidized
Lecithin!
Catabolism of Lipids
•  Lipases catalyze hydrolysis of bonds between fatty acid
and the rest of triacylglycerols
•  Phospholipases catalyze hydrolysis of bonds between
fatty acid and the rest of phosphoacylglycerols (生物膜
主要成份) Fatty Acid Activation
•  Fatty acid oxidation begins with activation(活化）
•  A thioester bond is formed between the carboxyl
group of the FA and the thiol of CoA-SH
脂肪酸 Acyl-CoA!
Liberation of Fatty Acids
from Triacylglycerols
The Role of Carnitine in Acyl-CoA Transfer
（活化的脂肪酸必須送到粒線體內進行分解）�
acyl-CoA crosses the
outer mitochondrial!
acyl group is then
transferred to carnitine
carried across the inner
mitochondrial membrane,
and transferred to
mitochondrial CoA-SH
Carnitine
translocase"
!
Carnitine
Palmitoyltransferase
(CPT-1) has specificity
for acyl groups between
14 and 18 carbons long
β-Oxidation
Cleavage of the carbon chain
by a reverse Claisen reaction!
Oxidation of the α,β
carbon-carbon single
bond to a carboncarbon double bond!
Oxidation of the β-hydroxyl
group to a carbonyl group!
Hydration of the carboncarbon double bond!
β-Oxidation Gives Rise to Nine 2-Carbon Units
Stearic acid 18 個碳： 8次 β-oxidation， 產生9個二碳單位Acetyl-CoA !
Energy Yield from FA Oxidation
•  The energy released by the oxidation of acetyl-CoA
formed by β-oxidation of FA can be used to produce
ATP
•  Eight cycles of β-oxidation are required for the
oxidation of Stearic acid to acetyl-CoA
Stearic acid (18碳）需經8次β-Oxidation 產生9個Acetyl-CoA!
進入TCA cycle!
TCA cycle
1 Acetyl-CoA產生：
1FADH2+1GTP+3NADH Energy Yield from FA Oxidation
•  The overall equation for oxidation of stearic acid can
be obtained by adding the equations for β-oxidation,
the citric acid cycle, and oxidative phosphorylation
Energy Yield from FA Oxidation
8X2.5=20"
27X2.5=67.5"
8X1.5=12"
9X1.5=13.5"
1 莫耳NADH進入電子傳遞鏈可產生 2.5莫耳ATP 1 莫耳FADH2可產生 1.5莫耳ATP 活化態 糖類、脂肪和蛋白質等物質在生物體內完全氧化會產生代謝
水。每100克糖氧化時可產生55毫升水，每100克脂肪可產生107
毫升水，每100克蛋白質可產生41毫升水 Catabolism of Odd-Numbered FA
•  Odd-numbered FA are
not frequently
encountered, but do
also undergo βoxidation
•  The last β-oxidation
cycle of a fatty acid with
an odd number of
carbons gives
propionyl-CoA(三個碳）
•  Propionyl-CoA can be converted to succinyl-CoA,
which plays a role in the citric acid cycle
Oxidation of an Unsaturated FA
•  A cis-trans isomerization is needed to convert
unsaturated FA to acetyl-CoA
•  This enzyme is known as an isomerase
•  Oxidation of unsaturated FA does not generate as
much ATP relative to saturated FA with the same #
of carbons
Oxidation of an Unsaturated FA
Ketone Bodies（酮體）�
•  Formation of ketone bodies occurs when the amount
of acetyl-CoA produced is excessive compared to
the amount of oxaloacetate available to react with it
•  Intake high in lipids and low in carbohydrates
•  Diabetes not suitably controlled
•  Starvation
TCA cycle
Ketone Bodies
acetyl-CoA!
• If an organism has an excess of acetylCoA, it produces ketone bodies.
• Ketone bodies are: acetone, βhydroxybutyrate, and acetoacetate
--formed principally in liver mitochondria
--can be used as a fuel in most tissues and
organs(心肌,腎臟 缺乏葡萄糖時的大腦）
• This situation can arise from an
excessive intake of fats compared to
carbohydrates, or from diabetes.
Q&A
Fatty Acid Biosynthesis（脂肪酸合成）�
•  Biosynthesis is not exact
reversal of oxidation
•  Biosynthetic reactions
occur in the cytosol（細
胞質）�
只有Citrate可以穿過粒線
體內膜，因此Acetyl-CoA
在粒線體內先轉變成citrate
再送出粒線體至細胞質內。 Fatty Acid Biosynthesis
•  Carboxylation of acetyl-CoA occurs in the cytosol
•  Catalyzed by acetyl-CoA carboxylase
•  Biotin is the carrier of the carboxyl group
•  Malonyl-CoA is key intermediate that is produced
Acetyl-CoA carboxylase
reactions
Acetyl-CoA"
Malonyl-CoA"
Biosynthesis of
Palmitate from Acetyland Malonyl-CoA
ACP: Acyl carrier protein"
此步驟為β氧化作用逆反應 6個Malonyl-CoA再分別加入 細胞質內脂肪酸合成
酶最多只做到C16， 之
後的碳鏈加長在內質網
（ER）及粒線體內
進行，此反應不需ACP C16"
Fatty acid synthase
ACP!
Sites of Fatty Acid Metabolism in an Animal Cell
Summary
• Acetyl-CoA is transported to the cytosol and converted to
malonyl-CoA
• The biosynthesis of FA proceeds by the addition of 2-carbon
units to the hydrocarbon chain. The process is catalyzed by
the fatty-acid synthase complex
Comparison of FA Degradation and Biosynthesis!
Triacylglycerol Biosynthesis
•  Lipids, such as,
triacylglycerols,
phosphoacylglycerol
s, and steroids are
derived from FA and
metabolites of FA
Biosynthesis of
phosphatidylethanolamine
in bacteria
Phosphatidylethanolamine
is found in all living cells,
composing 25% of all
phospholipids.
Biosynthesis of
phosphatidylethanolamine
in eukaryotes
The interconversion of phosphatidylethanolamine
and phosphatidylserine in mammals
In human physiology it is
found particularly in
nervous tissue such as
the white matter of brain,
nerves, neural tissue, and
in spinal cord, where it
makes up 45% of all
phospholipids."
Biosynthesis of Sphingosine/Ceramide
•  Require starting
materials palmitoyl-CoA
and serine
Cholesterol Biosynthesis
•  All carbon atoms of cholesterol and steroids
synthesized from it are derived from the two-carbon
acetyl group of acetyl-CoA
•  Involves many reaction steps
•  Involvement of isoprene units (C5H8) are key to the
biosynthesis of steroids and other biomolecules
known as terpenes (C5H8)n
Overall View of Cholesterol Biosynthesis
C5!
C2!
C6!
C30!
C27!
Cholesterol Biosynthesis
•  Synthesis begins with the
condensation of two
molecules of acetyl-CoA
HMG-CoA
synthetase"
•  Next, condensation with a
third molecule of acetyl-CoA
HMG-CoA"
抑制 lovastatin!
Mevalonate The Conversion
of Mevalonate
to Squalene
C6!
C6!
C5!
C5!
C15!
C30!
Squalene to
Cholesterol
The synthesis of bile acids from cholesterol
Cholate and Clycocholate（bile acids,
膽汁酸)： 使脂肪乳化
成微滴，增加了脂肪酶
的作用面積，幫助脂
肪分解與吸收。 Cholesterol is the
precursor for a
number of steroid
hormones
Role of Cholesterol in Heart Disease
•  Lipids are transported in the blood stream by
lipoproteins
•  Cholesterol and its fatty acid esters are packaged
into several classes of lipoproteins for transport
The LDL Particle
The Fate of Cholesterol
Atherosclerosis (動脈粥狀硬化）�
Q&A