Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH...
Transcript of Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH...
![Page 1: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/1.jpg)
Summary of β-oxidation
![Page 2: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/2.jpg)
Energy yieldThe ATP yield for every oxidation cycle is 14 ATP, broken down as follows:
1 FADH2 x 1.5 ATP = 1.5 ATP 1 NADH x 2.5 ATP = 2.5 ATP
1 acetyl CoA x 10 ATP = 10 ATP
For an even-numbered saturated fat (C2n), n - 1 oxidations are necessary and the final process yields an additional acetyl CoA.
In addition, two equivalents of ATP are lost during the activation of the fatty acid. Therefore, the total ATP yield can be stated as: (n - 1) * 14 + 10 - 2.Therefore, the total ATP yield can be stated as: (n - 1) * 14 + 10 - 2.
For instance, the ATP yield of palmitate (C16, n = 8) is:(8 - 1) * 14 + 10 - 2
106 ATPor
7 FADH2 x 1.5 ATP = 10.5 ATP 7 NADH x 2.5 ATP = 17.5 ATP
8 acetyl CoA x 10 ATP = 80 ATP ATP equivalent used during activation = -2
Total: 106 ATP
![Page 3: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/3.jpg)
What Are Ketone Bodies?
• They aren’t “bodies”, and• Only two are ketones• Same origin : acetyl-coA
![Page 4: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/4.jpg)
Synthèse à partir de l’acétylCoA (beta oxidation –catabolisme des AA)= cétogénèse
Catabolisme en acétylcoA = cétolyse
Enzymes sont mitochondriaux
![Page 5: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/5.jpg)
Besoins énergétiques couverts par glucose et lipides
Si glucose manque il y a les acides gras
Tous les tissus n’y ont pas accès : cerveau
On fait appel aux corps cétonique
Cétogénèse : exclusivement dans le foie. Normalement faible (importante en période de Jeune, diabète sucré non équilibré)
Cétolyse : myocarde, muscles , cerveau et cortex rénal
![Page 6: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/6.jpg)
Where Do These “Bodies” Come
From?• These 3 perfectly soluble small
molecules are• Produced in side reactions from
acetoacetyl-CoA at the penultimate step in β-oxidation,
• When there is excess acetyl-CoA for
β-ox
idat
ion
of F
As
condensation
• When there is excess acetyl-CoA for the TCA cycle
• This also produces free CoA• Thus allowing continued oxidation of
fatty acids in the liver• Acetone, the most volatile, is exhaled• Note reduction by β-HBdH and the
regeneration of S-CoA…
β-HBdH
Passent dans le sang et ….tissus extrahépatique
![Page 7: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/7.jpg)
Ketone Bodies from Liver Can Be Used as Fuel Elsewhere
• The ketone bodies are then exported to other tissues
• Renal cortex, skeletal and heart muscle, and brain (though it prefers glucose)
β-HBdH
(though it prefers glucose) can oxidize ketone bodies for use in their TCA cycles
• Apport glucidique insuffisant, les corps cétonique prennent le relais, glucose est réservé aux tissus glucodépendants
From TCA
To TCA
![Page 8: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/8.jpg)
• Cétogénèse est dépendante de la disponibilité mitochondriale de :
• Acétyl CoA. Défaut d’insuline (diabète, privation de glucide) accèlère lipolyse dans les tissus adipeux et on libère des acides gras captés comme substrats énergétique ou par le foie en tant que précurseurs des corps cétoniques
• En oxaloacétate• En oxaloacétate
Apport de glucide insuffisant, le taux d’oxaloacétate issu du pyruvate issue du glucose baisse et donc freine l’entrée de l’acétyl CoA dans le cycle de l’acide citrique
L’oxaloacétate issu du pyruvate provenant de lactate d’alanine, entièrement dirigé vers la néoglucogénèse
Acétyl coA issu de la beta oxydation s’engouffre dans la cétogénèse ce qui en plus libère du CoA permettant une beta oxidation continue
![Page 9: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/9.jpg)
Ketogenesis (Ketosis): Formation of Ketone Bodies
2 CH3COSCoA CH 3COCH2COSCoAThiolase
CH3COSCoA
Acetoacetyl CoA
HMG CoA
HO2C-CH2-C-CH2COSCoA
OH
CH3
ββββ-Hydroxy- ββββ-methylglutaryl CoA(HMG CoA)
HMG CoASynthase
Cholesterol(in cytosol)
Severalsteps
Ketogenesis(in liver: mitochon-
drial matrix)
![Page 10: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/10.jpg)
Ketogenesis: Formation of Ketone Bodies (Cont’d.)
HO2C-CH2-C-CH2COSCoA
OH
CH3
CH3COCH2CO2H
Acetoacetic Acid
HMG CoAlyase
- CH3COSCoA
HMG CoA- CO2
CH3COCH3
Acetone(volatile)
CH3CHCH2CO2H
OH
ββββ-Hydroxybutyrate
NADH + H+
NAD+Dehydrogenase
Ketone bodies are important sources of energy, especially in starvation
![Page 11: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/11.jpg)
Ketone Bodies As Energy Sources
ββββ-Hydroxybutyrate Acetoacetate Succinyl CoA
ββββ-Ketoacyl CoAtransferase
Succinic acidAcetoacetyl CoA
transferase
2 Acetyl CoAThiolase
TCA Cycle
![Page 12: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/12.jpg)
Rôle des acides gras
• Structural
• Fonctionnel
• énergétique
Exogènes : apport alimentaire couvre les besoins de l’organismeFoie , tissu adipeux et la glande mammaire en péride de lactation synthèse À partir de l’acetylcoA. Acide gras pouvant être remanier par élongation, désaturation
![Page 13: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/13.jpg)
![Page 14: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/14.jpg)
Fatty Acid Synthesis vs. Degradation
Intermediates
Synthesis Degradation
Linked to SH in Linked to CoASHProteins
Site
Enzymes
RedoxCoenzymes
Proteins (Acyl Carrier Proteins)
Cytosol Mitochondr ia
Components of Separate PolypeptidesSingle Peptide
NADP+ / NADPH NAD + / NADH
![Page 15: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/15.jpg)
Fatty Acid Biosynthesis
• Occurs in cytosol• Starts with acetyl CoA• Starts with acetyl CoA
• Problem:» Most acetyl CoA produced in mitochondria» Acetyl CoA unable to traverse mitochondrial
membrane
![Page 16: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/16.jpg)
Cytosol Mitochondria
Glucose Pyruvate Pyruvate Acetyl CoA
Fatty AcidsPyruvate
Dehydrogenase
BetaOxidation
Fatty Acids
Mitochondrial membrane
Oxalo-acetateCitrate
CitrateAcetyl CoA
ATP-CitrateLyase
Amino acids
Fatty Acids
Végétaux: chloroplastes
![Page 17: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/17.jpg)
Mitochondria
Cytosol
Acetyl CoA
TCA CycleCitrate
Citrate
Oxaloacetate
(2C) Acetyl CoAAcetyl CoA
HCO3
ATP(3C) Malonyl CoA
COAcetyl CoA Carboxylase(biotin)
CO2
NADPH
4C Butyryl CoA
2C Acetyl CoA 3C Malonyl CoA
6C Caprayl CoA
CO2
NADPH
Fatty Acid Synthase
Complexe Enzymatique7 activités enzymatiques+ acyl protéine
propionylcoA
Source NADPHDécarboxylation malate –pyruvate (adipeux)Voie des pentoses phosphates
![Page 18: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/18.jpg)
![Page 19: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/19.jpg)
Fatty Acid Biosynthesis: Formation of Malonyl CoA
CH3COSCoA + ATP + HCO 3- -O2CCH2COSCoA
Acetyl CoACarboxylase Malonyl CoA
+ ADP + P i + H+
• Committed step in fatty acid synthesis• Reaction is irreversible• Regulation of acetyl CoA carboxylase activity:
by palmitoyl CoAby citrate
• Malonyl CoA inhibits carnitine acyl transferase I • Blocks beta oxidation
![Page 20: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/20.jpg)
Fatty Acid Biosynthesis:Role of Acyl Carrier Proteins
CH3COSCoA CH3CO-S-ACP
AcetylTransferase
Malonyl
Acetyl ACP
-O2CCH2COSCoA -O2CCH2CO-S-ACP
MalonylTransferase
Malonyl ACP
ACP = Acyl carrier protein
![Page 21: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/21.jpg)
![Page 22: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/22.jpg)
![Page 23: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/23.jpg)
Fatty Acid Biosynthesis:Formation of Acetoacetyl ACP
CH3CO-S-ACP + -O2CCH2CO-S-ACPββββ-Ketoacyl ACP
CH3COCH2CO-S-ACP + CO2Acetoacetyl ACP
ββββ-Ketoacyl ACPSynthetase
![Page 24: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/24.jpg)
Fatty Acid Biosynthesis:Formation of Butyryl ACP
CH3COCH2CO-S-ACP CH3CCH2CO-S-ACP
OH
HAcetoacetyl ACP
ββββ-Ketoacyl ACPreductase
NADPH NADP+ HAcetoacetyl ACPββββ-D-Hydroxybutyryl ACP
NADPH+ H+
NADP+
CH3C=C-CO-S-ACP
H
H
ββββ-Hydroxyacyl ACPdehydratase- H2O
Crotonyl ACP
CH3CH2CH2CO-S-ACP
Butyryl ACP2,3-trans-Enoyl ACPreductase
NADPH+ H+
NADP+
![Page 25: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/25.jpg)
Fatty Acid Biosynthesis:Sources of NADPH
Pentose Phosphate Pathway:
CHO
OHHO
CO2-
OHHO
NADP+NADPH+ H+ NADP+
NADPH+ H+ OH
OHO
OHOHOP
HOOHOHOP
HO
CO2
OHOHOP
Ribulose-5-phosphate6-Phospho-
gluconateGlucose-6-phosphate
Malic Enzyme:
HO-CH-CO2-
CH2CO2-Malate
CO2
NADP+
NADPH+ H+
Malic Enzyme
CH3CCO2-
O
Pyruvate
![Page 26: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/26.jpg)
Mitochondria
Cytosol
Acetyl CoA
TCA CycleCitrate
Citrate
Oxaloacetate
(2C) Acetyl CoAAcetyl CoA
HCO3
ATP(3C) Malonyl CoA
COAcetyl CoA Carboxylase(biotin)
CO2
NADPH
4C Butyryl CoA
2C Acetyl CoA 3C Malonyl CoA
6C Caprayl CoA
CO2
NADPH
Fatty Acid Synthase
Complexe Enzymatique7 activités enzymatiques+ acyl protéine
Bactéries et végetaux : Poly indépendantesAnimaux: dimère
propionylcoA
Source NADPHDécarboxylation malate –pyruvate (adipeux)Voie des pentoses phosphates
![Page 27: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/27.jpg)
Fatty Acid Biosynthesis:Chain Elongation
CH3CH2CH2CO-S-ACP -O2CCH2CO-S-ACP+
CH3CH2CH2COCH2CO-S-ACP
CH2CH2CH2CHCH2CO-S-ACP CH3CH2CH2C=CCO-S-ACP
H
H
OH
![Page 28: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/28.jpg)
Fatty Acid Biosynthesis:Chain Elongation (Cont’d)
CH3(CH2)3CH2CO-S-ACPCH3CH2CH2C=CCO-S-ACP
H NADPH+ H+
NADP+
H
CH3(CH2)13CH2CO-S-ACP
5 Cycles
Palmitoyl ACPCH3(CH2)13CH2CO2
-
Palmitate
![Page 29: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/29.jpg)
Further Processing of Fatty Acids: Elongation
CH3(CH2)13CH2CO2-
Palmitate
Thiolase
CH3COSCoA
In mitochondria andat surface of endoplasmic reticulum
Navette carnitinepalmitoylcoA
CH3(CH2)13CH2COCH2COSCoA
CH3(CH2)13CH2CCH2COSCoA
OH
H
NADH + H+
NAD+
Thiolase
Dehydrogenase
L-ββββ Configuration
palmitoylcoA
![Page 30: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/30.jpg)
Further Processing of Fatty Acids: Elongation (Cont’d)
CH3(CH2)13CH2CCH2COSCoA
OH
H- H2O
CH3(CH2)13CH2C=CCOSCoA
H
H
- H2OHydratase
CH3(CH2)13CH2CH2CH2COSCoA
Stearoyl CoA
NADPH + H+
NADP+
Dehydrogenase
![Page 31: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/31.jpg)
Further Processing of Fatty Acids: Unsaturation
CH3(CH2)13CH2CH2CH2COSCoAStearoyl CoA
Stearoyl CoADesaturase
O2
CH3(CH2)7C=C(CH2)7COSCoA + H2O
H HOleoyl CoA
This reaction occurs in eukaryotesEndoplasmic reticulum membrane
Desaturase
![Page 32: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/32.jpg)
Further Processing of Fatty Acids: Polyunsaturation
CH3(CH2)7C=C(CH2)7CO2H
H HOleic acid
Plants: Further unsaturationoccurs primarily in this region
Animals: Further unsaturationoccurs primarily in this region
(18:1∆∆∆∆9)
9
occurs primarily in this region occurs primarily in this region
CO2H
Linoleic acid (18:2 ∆∆∆∆9, 12)
12 9
Linolenic acid (18:3 ∆∆∆∆9, 9, 9, 9, 12, 15)
15 12 9
Essential dietaryfatty acids in mammals
CO2H
![Page 33: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/33.jpg)
Formation of Arachidonate in Mammals
Linoleic acid As CoA ester:1) Elongation
CO2H
CO2H14 11 8 5
Arachidonic acid (20:4 ∆∆∆∆5, 5, 5, 5, 8, 11, 14)(Eicosa-5,-8,11,14-tetraenoic acid)
1) Elongation2) Desaturation x 2
Prostaglandins
![Page 34: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/34.jpg)
Omega-3 Fatty AcidsCO2H
CO2H
ωωωω-3 double bond Eicosapentaenoic acid (20:5 ∆∆∆∆5, 5, 5, 5, 8, 11, 14, 17)
CO2H
Docahexaenoic acid (22:6 ∆∆∆∆4, 4, 4, 4, 7, 10, 13, 16, 19)
• Found in fish oils, esp. cold water fish• Important in:
Growth regulationModulation of inflammationPlatelet activationLipoprotein metabolism
![Page 35: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/35.jpg)
Metabolite Regulation of Fatty Acid Synthesis and Breakdown
Pyruvate Acetyl CoA Malonyl CoA
Citrate
Stimulates
BetaBlocks
Glucose
Pyruvate Acetyl CoA Malonyl CoA
Palmitoyl CoA
Inhibits
BetaOxidation
![Page 36: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/36.jpg)
Hormonal Regulation of Fatty Acid Synthesis and Breakdown
ATP cAMP AMPAdenylyl cyclase Phosphodiesterase
Stimulates
Glucagon
Stimulates
Insulin
Stimulates
Activates Protein Kinase
Inactivates ACC byphosphorylation
Inhibition offatty acidsynthesis
Activates triacyl-glycerollipase
Inactivateslipase
![Page 37: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/37.jpg)
Synthesis of Phosphatidic Acid
O-
O
-
O
CH2O-P-O-
CH2O2C-R1
CHO2C-R2C=O
CH2OH
CH2O-P-O-CH2OH
CHOH
CH2OH
Dihydroxyacetone Phosphate
(from glycolysis)
Glycerol
O- O-
O
O
O
CH2OC-R1
CHOC-R2
CH2OC-R3
CHO2C-R2
CH2O2C-R1
CH2OH
CH2O-P-O2 CH2OH
Phosphatidic acid
Diacylglycerol(important incell signaling)
R3COSCoA
Diacylglycerolacyltransferase
Triacylglycerol
Triglyceride synthase(membrane du réticulum lisse)
![Page 38: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/38.jpg)
Synthesis of Glycerophospholipids
CH2OH
CH2O2C-R1
CHO2C-R2
N
N
NH2
O
O
OHOH
R3NCH2CH2OPOPO+
R=H; CDP ethanolamine
+ Transferase
O
CHO2C-R2
CH2O2C-R1
CH2O-P-O-CH2CH2R3CH2OHR=H; CDP ethanolamineR=CH3; CDP cholineCDP = cytidine diphosphate
DiacylglycerolR3=NH3; Phosphatidylethanolamine
R3=N(CH3)3; Phosphatidylcholine
O-
O
CO2-
CH2O-P-O-CH2CHNH 3
CH2O2C-R1
CHO2C-R2
+
+
CO 2-
HOCH 2CHNH3
HOCH 2CH2NH3
+ Serine
Ethanolamine
O-CH2O-P-O-CH2CH2R3
+
+
Phosphatidylserine
![Page 39: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/39.jpg)
Synthesis of Glycero -phospholipids (Cont’d)
O
CHO2C-R2
CH2O2C-R1
CH2O-P-O-CH2O-CDP
CH2O2C-R1
CHO2C-R2 Phosphatidyl-inositol
O-
O
OH OH
CH2O-P-O
CH2O2C-R1
CHO2C-R2
O-CH2O-P-O CH2O-CDP
Phosphatidic acid Cytidine diphosphate (CDP) diacylglycerol OH
OHHO
OH
OH
OPO3H2H2O3PO
OH OH
OPO3H2
CH2OH
CH2O2C-R1
CHO2C-R2+
Diacylglycerol (DAG)
Phospholipase C
Both IP 3 and DAG are important second messengersin cell signaling pathways
Inositol-1,4,5-triphosphate (IP 3)
![Page 40: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/40.jpg)
Synthesis of Glycero -phospholipids (Cont’d)
CHO C-R
CH2O2C-R4CH2O2C-R1
CHO2C-R2
CH2O2C-R1
CHO2C-R2
O-
O O
O-OH
CHO2C-R3
CH2O-P-O-CH2CHCH2-O-P-O-CH2
CHO2C-R2
CH2O-CDP
CHO2C-R2
Cytidine diphosphate (CDP) diacylglycerol Cardiolipin
![Page 41: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/41.jpg)
Quite a VarietyNote trends:
MP vs lengthMP vs saturation
Solubility vs length
Uns
at’d
Sat
’d
Table 10-1
Uns
at’d
Sat
’d
![Page 42: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/42.jpg)
Do Classes of Lipids Make Sense?
Glycerol backbone Sphingosine backbone
![Page 43: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/43.jpg)
Sphingolipids
Sphingosine,Is a fatty amine,A feature that’sOutlined in green!
Some rhymes…
Outlined in green!
No glycerolAt all!
![Page 44: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/44.jpg)
Sterols: Structural Lipids, Hormone Precursors, and Detergents
• Have a structural role in most eukaryotic membranes (we’ll see why later)
Fig. 10-16
• Hormone derivatives regulate gene expression
• Bile acids are polar derivatives that help emulsify dietary fats
![Page 45: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/45.jpg)
Turnover of Membrane Phospholipids Exploits Specific Enzymes
![Page 46: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/46.jpg)
Glycerophospholipid synthesis starts with phosphatidic acid or diacylglycerol
![Page 47: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/47.jpg)
Phosphatidylserine is formed from phosphatidylethanolamine byan exchange of the polar head group
Figure 25-79 Phosphatidylserine synthesis .Page 971
![Page 48: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/48.jpg)
Ceramide comes from Palmitoyl~CoA, serine, and an acyl~CoA
![Page 49: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/49.jpg)
Cholesterol is synthesized from acetyl~CoA in three stages
1. Synthesis of isopentenyl pyrophosphate, an activated isoprene unit.
2. Condensation of 6 molecule of IPP to form squalene.
3. Squalene cyclizes and the tetracyclic product is converted to cholesterol.
Cholesterol is a component of membranes and a precursor to steroids and bile salts.
![Page 50: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/50.jpg)
Sphingolipid biosynthesis
![Page 51: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/51.jpg)
Stage 2: the condensation of isoprenoid units
mechanism of IPP isomeraseHMG-CoA reductase catalyzes an irreversible reactionthat is the committed step. It is highly regulated.
![Page 52: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/52.jpg)
Likely mechanism for the prenyl transferase reaction
Page 947
![Page 53: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/53.jpg)
Formation of squalene
Figure 25-47 Formation of squalene from isopenteny l pyrophosphate and dimethylallyl
pyrophosphate.
Page 946
![Page 54: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/54.jpg)
Stage three: Lanosterol is produced by squalene cyclization
Figure 25-42 Squalene. ( a) Extended conformation. Each box contains one isop rene unit. (b) Folded in preparation for cyclization as predicte d by Bloch and Woodward.
The cyclization reaction occurs in two steps: Squalene epioxidase forms 2,3 oxidosqualene,lanosterol synthase brings about cyclization by protonation of the epioxide, the cyclizationinvolves a series of hydride and methyl shifts.
![Page 55: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/55.jpg)
The squalene epioixidase reaction
![Page 56: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/56.jpg)
The lanosterol synthase reaction
enzyme protonates the epioxide, forminga cation.
a series of methyl and hydride migrationsa series of methyl and hydride migrationsprobably yeilds carbocation at position C8
elimination of a proton gives C8-C9double bond
![Page 57: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/57.jpg)
Pentose Phosphate Pathway
• Produces reducing power• Produces ribose and other pentoses
Glucose 6-phosphate ----------> ----------> C5 -----------> ribose 5P
![Page 58: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/58.jpg)
Overview• Important products of PPP
– Production of NADPH – the pyridine nucleotide used for reductive biosynthesis• Fatty acids• Cholesterol• Nucleic acids• Nucleic acids
– Formation of ribose 5-phosphate for ribonucleotides• RNA, DNA, certain coenzymes
• Mammary glands, liver, adrenal glands, adipose– Not in brain and muscle
• Enzymes of pathway are cytosolic
![Page 59: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/59.jpg)
NADPH
• Enzymes that have a high affinity for NADPH have a 1000-fold lower 1000-fold lower affinity for NADH.
![Page 60: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/60.jpg)
Phase oxidative(irréversible)
D’isomérisation
Pentose Phosphate Pathway
Non-oxidative
![Page 61: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/61.jpg)
Pentose Phosphate Pathway: Oxidative Phase
Production of 2 NADPH and ribulose-5-phosphate from glucose-6-phosphate
Étape limitante dépendanteDu ratio NADP/NADPH
glucose-6-phosphate
![Page 62: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/62.jpg)
![Page 63: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/63.jpg)
Pentose Phosphate Pathway: Nonoxidative Phase
Si besoin que de NADHP, ribose 5 phosphate retourne à la glycolyse.
Comment passer C5 à un C6 sans fixation de Comment passer C5 à un C6 sans fixation de carbone
6C5 donneront 5C6
![Page 64: Summary of β-oxidation€¦ · Glycerol O O O O CH 2OC-R 1 CHOC-R 2 CH 2OC-R 3 CHO 2C-R 2 CH 2O2C-R 1 CH 2OH Phosphatidic acid Diacylglycerol (important in cell signaling) R3COSCoA](https://reader033.fdocuments.in/reader033/viewer/2022053101/605f6193997d3b7338172057/html5/thumbnails/64.jpg)
+xyulose-5-P � G-3-P + F-6-P