Wk12 fatty acid metabolism 1

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