BiochemistryBiochemistrySixth EditionSixth Edition
Chapter 22:Fatty Acid Metabolism
Fatty Acid MetabolismFatty Acid Metabolism
身體脂肪的主要成分又稱 neutral fat
Triacylglycerol Triacylglycerol or or
TriglycerideTriglyceride
Adipocyte
TGTG
Four metabolic stepsFour metabolic steps
分解脂肪的水解酵素— Lipase
食物中的 TG
腸道內腔 黏膜內腔
Apoliporotein B-48Apoliporotein B-48(Apo B-48)(Apo B-48)
運送脂溶性 運送脂溶性 Vitamin Vitamin 與 與 cholesterolcholesterol
Chylomicron Chylomicron 之生成與作用之生成與作用
進入血液進入血液
Three Steps of Triglyceride DegradationThree Steps of Triglyceride Degradation
Step 1: TG Step 1: TG fatty acidfatty acid + glycerol + glycerol
Step 2: Fatty acid was Step 2: Fatty acid was transportedtransported to Mitochondrial to Mitochondrial
Step 3: Fatty acid Step 3: Fatty acid Acetyl CoAAcetyl CoA TCA cycle TCA cycle
Step 1: TG Step 1: TG fatty acidfatty acid + glycerol + glycerol
Regulation of TG Lipase activityRegulation of TG Lipase activity
inacitveinacitve acitveacitve
inacitveinacitve acitveacitve
Glycagon & EpinephrineGlycagon & Epinephrine
GlycolysisGlycolysis
From Glycerol to GlycolysisFrom Glycerol to Glycolysis
DHAP GA3P
Triglyceride Degradation
Acyl CoA synthethase
Before β-oxidation
Fatty acid
CoA
Acyl CoA
Acyl CoA synthetaseFatty acid
CoA
Acyl CoA
AMPAMP
Fatty acidFatty acid
Step 2: Fatty acid was Step 2: Fatty acid was transportedtransported to Mitochondrial to Mitochondrial
Fatty acidFatty acid
β-oxidation
β-oxidation
Reaction at β-Carbon
Step 1 of β-oxidation produces FADH2 Step 1 of β-oxidation produces FADH2
1.5 ATP1.5 ATP
Step 1 of β-oxidation—oxidation by FADStep 1 of β-oxidation—oxidation by FAD
Acyl CoA Acyl CoA dehydrogenasedehydrogenase
Step 2 of β-oxidation—hydrationStep 2 of β-oxidation—hydration
Enoyl CoA Enoyl CoA hydratasehydratase
Step 3 of β-oxidation—oxidation by NAD+Step 3 of β-oxidation—oxidation by NAD+
L-3-hydrooxyacyl CoA L-3-hydrooxyacyl CoA dehydrogenasedehydrogenase
Step 4 of β-oxidation—Thiolysis by CoAStep 4 of β-oxidation—Thiolysis by CoA
ββ-ketothiolase-ketothiolase
- 1 ATP
+ 1 FADH2
+ 1 NADH
Shortened by 2 carbons per cycle of β-oxidation
Acetyl CoA
Acetyl CoA
Acetyl CoA
.
.
.
.
TCA cycle
Cn
Cn-2
Cn-2-2
Cn-2-2-2
Pamitate (16:0)
Acetyl CoA Acetyl CoA
7 ATP
7 FADH2 = 7*1.5 ATP
7 NADH = 7*2.5 ATP
7 Acetyl CoA TCA cycle
7 ATP
7 FADH2 = 7*1.5 ATP
7 NADH = 7*2.5 ATP
7 Acetyl CoA TCA cycle
7 cycles of β-oxidation
TCA cycle
Pamitate (16:0)
生 產 Acetyl CoA
耗掉 1 ATP
生 產 7 FADH2 = 7*1.5 ATP
生 產 7 NADH = 7*2.5 ATP
生 產 7 Acetyl CoA TCA cycle
7 cycles of β-oxidation
TCA cycle
β-oxidation of unsaturated fatty acid
1 Double bond1 Double bond
2 Double bond2 Double bond
The final metabolite of β-oxidation of Odd-Chain fatty acid
TCA cycle?
TCA cycle
The metabolism of Propionyl CoA
Propionyl CoA Carboxylase
Methylmalonyl CoA mutase
Methylmalonyl CoA mutaseCoenzyme : Vit B12
PeroxisomeMitochondrial
β-oxidation
β-oxidation of Eukaryotic cell β-oxidation of Eukaryotic cell
Long chain fatty acid
Octanoyl CoA
Acetyl CoA
The first step of β-oxidation in peroxisome of Eukaryotic cell
From acetyl CoA to Ketone body
Lack of Glucose
Acetyl CoA formed from β-oxidation would not be
metabolized into TCA cycle
Acetyl CoA formed from β-oxidation would not be
metabolized into TCA cycle
Acetyl CoA Acetyl CoA
The accumulated Acetyl CoA metabolized into ketone body pathway
The accumulated Acetyl CoA metabolized into ketone body pathway
Ketone body biosynthesis pathway Ketone body biosynthesis pathway
Acetyl CoA Acetyl CoA
Acetyl CoA Acetyl CoA
Acetyl CoA Acetyl CoA
Acetyl CoA Acetyl CoA
Acetyl CoA Acetyl CoA
Acetyl CoA Acetyl CoA
HMG CoA HMG CoA
Acetyl CoA Acetyl CoA
Rich in NADHRich in NADH
Lack of NADHLack of NADH
TCA cycleTCA cycle
GlycolysisGlycolysis
GlucoseGlucose
TCA cycleTCA cycle
COCO22 + H + H22OO
Lack of Glucose
Acetyl CoA formed from β-oxidation would not be
metabolized into TCA cycle
Acetyl CoA formed from β-oxidation would not be
metabolized into TCA cycle
Acetyl CoA Acetyl CoA
The accumulated Acetyl CoA metabolized into ketone body pathway
The accumulated Acetyl CoA metabolized into ketone body pathway
Biosynthesis of Fatty Acid
1. Biosynthesis in cytoplasm2. Acyl Carrier Protein (ACP)3. Fatty acid synthase4. Adding by 2 carbons per cycle5. NADPH 6. Elongation until palmitate (16:0) with Fatty
acid synthase complex
The committed step of synthesis of Fatty Acid
Acetyl CoA CarboxylaseAcetyl CoA Carboxylase
Acetyl ACPAcetyl ACP& Malonyl ACP& Malonyl ACP
Acetyl CoAAcetyl CoA& &
Malonyl CoAMalonyl CoA
Binding with ACPBinding with ACP
Acetyl CoA Acetyl CoA should be transported to should be transported to cytoplasm via citrate for fatty acid synthesiscytoplasm via citrate for fatty acid synthesis
ATP-citrate lysaseATP-citrate lysase
Malate DHaseMalate DHase
Malate enzymeMalate enzyme
Sources of NADPHSources of NADPH
Regulation of Acetyl CoA carboxylaseRegulation of Acetyl CoA carboxylase
BiochemistrySixth Edition
Chapter 26The Biosynthesis of Membrane
Lipids and Steroids
Copyright © 2007 by W. H. Freeman and Company
Berg • Tymoczko • Stryer
HMG- CoA HMG- CoA reductasereductase
Lipoprotein metabolism
HMG-CoA reductase inhibitor— Competitive inhibition
The structure is similar to HMG-CoA