Lipids and Fatty Acids - UBC...
Transcript of Lipids and Fatty Acids - UBC...
Lipids and Fatty Acids Objectives: 1. What are Lipids?
• properties • glycerolipids vs. isoprenoids • glycerolipid structure • glycerolipid nomenclature
2. Fatty acid biosynthesis
• Cellular localization • Substrate and its origin • Enzymes of de novo fatty acid synthesis • De novo fatty acid elongation (C2->C18)
References: Buchanan et al. 2000. Biochemistry and Molecular Biology of Plants. American Society of Plant
Physiologists, Rockville MD. Chapter 10.
What are lipids?
Triacylglycerol (TAG)
Vitamin D2
What are lipids?
Macromolecules defined on the basis of their physical properties:
• Insoluble in water • Soluble in non-polar organic solvents
Lipids are chemically heterogeneous
Vitamin D2
Originate from different biosynthetic pathways
Triacylglycerol (TAG)
What are lipids?
Macromolecules defined on the basis of their physical properties:
• Insoluble in water • Soluble in non-polar organic solvents
Heteropolymers consisting of different subunits (glycerolipids), or do not form polymers (isoprenoids=terpenoids)
Glycerolipids Fats and oils
H C
H C
H C
H
H
H C
H C
H C
H
H
1
2
3 H C
H C
H C
H
H
H C
H C
H C
H
H
1
2
3
Glycerol backbone
Fatty acyl group
Triacylglycerol (TAG)
sn-1
sn-2
sn-3
Triacylglycerols form oil droplets
Oilseed embryo
Glycerolipids
Acyl group
Membrane lipids
HOH
OH
H2COH
HH
H
O O H OH
H C
H
H C
H C
H
Glycerol backbone
Fatty acyl group
Head group
Monogalactosyldiacylglycerol (MGDG)
sn-1
sn-3
sn-2
Glycerolipids
Acyl group
Membrane lipids
H C
H
H C
H C
H
Glycerol backbone
Fatty acyl group
Phosphatidylcholine (PC)
sn-1
sn-3
sn-2
O
O
O
O
O
P
Head group
1. Glycerol backbone
2. Fatty acyl groups on sn-1 and sn-2 positions
• Saturated – no double bonds • Unsaturated – one or multiple double
bonds
3. Head group on sn-3 position
• Sugar moiety -> Glycolipids • Phosphate + alcohol -> Phospholipids • No head group -> Acyl glycerols
Glycerolipid nomenclature
Oleic acid 18:1 Δ9 or ω9
Number of Carbon atoms
Number of Double bonds
Trivial name
Double bond position (counting from carboxyl end or methyl end)
cis configuration unless indicated
Fatty acid nomenclature -
H C C
H - -
H C C
H - -
H C - H C C
H C H
-
trans double bond E configuration Carboxyl end
Methyl end
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
O
HO C - C
H
- C H
- H C H
- H C H -
H C H
- H C H
- H C H
- H C H
- H C H
- H C H
H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
O
HO C - C
H
- C H
- H C H
- H C H -
H C H
- H C H
- H C H
- H C H
- H C H
- H C H
H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
O
HO C - C
H -
H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
O
HO C - C
H C H
- C H
- H C H
- H C H -
H C H
- H C H
- H C H
- H C H
- H C H
- H C H
H
- C H - C
H
- H C H
- H C H -
H C H
- H C H
- H C H
- H C H
- H C H
- H C H
H
- H C H
- H C H -
H C H
- H C H
- H C H
- H C H -
H C H
- H C H -
H C H
- H C H
- H C H
- H C H
- H C H
- H C H -
H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
- H C H
cis double bond Z configuration
Common Eukaryotic Fatty Acids
Unsaturated fatty acids
16:0 Hexadecanoic acid Palmitic acid
18:0 Octadecanoic acid Stearic acid
16:1 Δ7 Hexadecenoic acid Palmitoleic acid
16:1 Δ3 t trans-hexadecenoic acid
16:2 Δ7Δ10 Hexadecadienoic acid
16:3 Δ7,Δ10,Δ13 Hexadecatrienoic acid 18:1 Δ9 Octadecenoic acid Oleic acid
18:2 Δ9,Δ12 Octadecadienoic acid Linoleic acid
18:3 Δ9,Δ12,Δ15 Octadecatrienoic acid Linolenic acid
Saturated fatty acids
Symbol Systematic name Trivial name
• 16 or 18-carbon unbranched acyl chain (even number)
Characteristics of Common Fatty Acids
• Zero to 3 double bonds
• Double bonds are methylene interrupted (Allylic)
=CH
-CH
-HCH
-CH
-HCH
-HCH
=CH
- =CH
-CH
-HCH-C
H-
HCH
-CH
-HCH
-HCH
=CH
-
Allylic CH2 group
• Components of membrane and storage lipids
De novo Fatty Acid Synthesis
Fig. 10-9
Site: PLASTID Substrate: acetyl-CoA
De novo Fatty Acid Synthesis
Fig. 10-11
Acetyl-CoA Carboxylase reaction 1st committed step in fatty acid synthesis
FAS Enzymes
ACP = Acyl Carrier Protein – primer for FAS, carries the fatty acyl chain
6. ER = 2-3 trans enoyl-ACP reductase
Enzymes:
1. ACCase = Acetyl-CoA Carboxylase
3. CONDENSING ENZYMES – key enzymes of FAS involved in C-C bond formation (CO2 release – IRREVERSIBLE!)
• KAS III – C2 • KAS I – C4-C14 • KAS II – C16
– different substrate specificities:
4. KR = 3-ketoacyl-ACP reductase
5. DH = 3-hydroxyacyl-ACP dehydratase
2. Malonyl-CoA:ACP transacylase
Organization of FAS Enzymes
TYPE I (Animals and Fungi)
TYPE II (Plants and Bacteria)
Location: Cytosol
Location: Plastid stroma
Organization: A complex of 2 large subunits (250 kDa each) catalyzing all
the reactions of FAS
Organization: Enzyme activities reside on individual proteins – this reflects prokaryotic origin of plastids
KAS KR
DH ER
KAS KR
DH ER
Fatty Acid Synthesis
Ohlrogge and Browse (1995) Plant Cell 7:795
KASIII
ER
DH
KR
KAS I
ACC
TA
Fatty Acid Synthesis
FAS
16:0-ACP
18:0-ACP
18:1-ACP
FATB
FATA
LACS
LACS
16:0-CoA
18:1-CoA
AT
AT
16:0
18:1 Chl
orop
last
lipi
ds
DES
FAS = fatty acid synthesis
FAT = acyl-ACP thioesterase
AT = acyl transferase
LACS = acyl-CoA synthetase
DES = stearoyl-ACP desaturase
Main products of FAS are 16:0 and 18:1
AT 18:0 18:0-CoA LACS
FATB KASII
Main products of FAS are 16:0 and 18:1
Export to the ER Lipid synthesis in the chloroplast
AT FAT
How do we know that?
From (14C)-acetate labeling experiments of isolated plastids in vitro
C16 and C18 fatty acyl chains get radioactively labeled