Chapter 21: Lipid Biosynthesis

1
Chapter 21 Lipid Biosynthesis

• Dr. Clower
• CHEM 4203

2
Lipid Biosynthesis

• Essential to all organisms
• Functions of lipids
• In this chapter
• Fatty Acids
• Triacylglycerides
• Membrane lipids
• Cholesterol

3
Biosynthesis of Fatty Acids

• Reverse of b-oxidation?
• Condensation of 2-carbon units
• Differences between biosynthesis and b-oxidation
• Three processes
• Transport of acetyl-CoA into cytosol
• Formation of malonyl-CoA
• Assembly of fatty acids

4
I. Transport of Acetyl-CoA into the Cytosol
5
Shuttle of Acetyl Groups from Mitochondria into
the Cytosol
6
II. Formation of Malonyl-CoA
7
The Acetyl-CoA Carboxylase Reaction
8
Role of Biotin in Carboxylation Reactions
9
III. Assembly of Fatty Acids
10
The Four-step Sequence
11
Synthesis of Palmitate
12
E. Coli Fatty Acid Synthase
13
Acyl Carrier Protein
14
Transfer of Acetyl and Malonyl Groups to Fatty
Acid Synthase
15
Synthesis Reactions
16
Synthesis Reactions
17
Synthesis Reactions
18
Synthesis Reactions
19
Synthesis Reactions
20
What is the overall reaction for the synthesis of
palmitate from acetyl-CoA?
21
Structures of Fatty Acid Synthases
22
Localization of Pathways
23
Sources of NADPH
24
Regulation of Fatty Acid Synthesis
25
What are some significant differences between FA
oxidation and synthesis?
26
Elongation and Desaturation
27
NextSynthesis of TAGs
28
Biosynthesis of Triacylglycerols

• Fatty acids can be incorportated into TAGs or
  phospholipids
• Both require the synthesis of fatty acyl esters
  of glycerol
• Fatty acyl-CoA
• Activated fatty acids
• L-Glycerol-3-phosphate
• From DHAP or glycerol

29
Biosynthesis of TAGs
30
Regulation of TAG Biosynthesis
Triacylglycerol Cycle
31
Glyceroneogenesis
32
Regulation
33
Biosynthesis of Membrane Lipids

• Steps to formation of glycerphospholipids and
  sphingolipids
• Synthesis of backbone (glycerol or sphingosine)
• FA esterification (or amidation)
• Head group attachment (e.g., choline, serine,
  ethanolamine, etc.)
• Head group modification

34
Synthesis of Phosphatidic Acid
35
Formation of Phosphodiester Bond
36
Synthesis of Sphingolipids

• Synthesis of 18-C sphinganine
• From palmitoyl-CoA and serine
• Attachment of FA
• Amide linkage
• Desaturation
• Ceramide
• Attachment of head group
• Cerebroside or sphingomyelin

37
Synthesis of Sphingolipids
38
NextCholesterol
39
Cholesterol

• An isoprenoid
• Cell membrane constituent
• Precursor to steroid hormones, bile acids
• Associated with cardiovascular disease
• Obtained in the body
• Diet
• Synthesis

40
Biosynthesis of Cholesterol
41
Biosynthesis of Cholesterol

• 5 stages
• Formation of mevalonate
• Conversion to activated isoprene
• Polymerization of isoprene
• Cyclization of squalene
• Modification of structure

42
Stage 1 Synthesis of Mevalonate
43
Stage 2 Conversion of Mevalonate to Activated
Isoprene Units
44
Stage 3 Formation of Squalene
45
Stage 4 Cyclization
46
Regulation of Cholesterol Synthesis
SREBP Sterol regulatory element-binding
proteins SCAP SREBP cleavage-activating protein
47
Fate of Cholesterol

• Incorporated into hepatocyte membranes
• Exported
• Bile acids
• Cholesterol esters
• Free cholesterol

48
Lipoproteins
49
Lipoproteins and Lipid Transport
50
Summary of Lipid Metabolism
From Voet, Voet and Pratts Fundamentals of
Biochemistry