12 Fatty Acid and TAG Biosynthesis 20141115
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Transcript of 12 Fatty Acid and TAG Biosynthesis 20141115
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Malic enzyme: Malate Pyruvate + CO2
NADP+ NADPH + H+
Glyoxysomes
Subcellular Locations of Lipid Metabolism
Glyoxysomes
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Fatty Acid Biosynthesis
Different enzymes from those in fatty acid -oxidation Activation of acetyl-CoA required Spiral metabolic pathway
Formation of Malonyl-CoA by acetyl-CoA carboxylase - An irreversible and committed step for fatty acid biosynthesis in
animals - Biotin as a prosthetic group in the enzyme
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Formation of Palmitic Acid (16:0) by Fatty Acid Synthase - A multifunctional enzyme complex (7 enzymatic activities)
Summary of 2 parts
Formation of 7 malonyl-CoA:
7 acetyl-CoA + 7 CO2 + 7ATP → 7 malonyl-CoA + 7ADP + 7Pi
7 cycles of condensation and reduction:
Acetyl-CoA + 7 Malonyl-CoA + 14 NADPH + 14 H+
Palmitic acid + 7 CO2 + 8 CoA-SH + 14 NADP+ + 6 H2O
Acyl carrier protein (ACP) - A protein co-enzyme for attachment of substrates and intermediates
during fatty acid biosynthesis - Part of the fatty acid synthase complex
Overall reaction:
8 Acetyl-CoA + 7 ATP + 14 NADPH + 14 H+
Palmitic acid + 7 ADP + 7 Pi + 6 H2O + 8 CoA-SH (Co-enzyme A)
H – SACP (Abbreviated form)
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Fatty acid biosynthesis by fatty acid synthase (FAS) complex:
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Initiation reactions of fatty acid biosynthesis
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HS-Cys (FAS),
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Fatty acid catabolism vs anabolism
oxidation
hydration
oxidation
thiolysis
reduction
dehydration
reduction
condensation
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Tricarboxylate transport system
Inner membrane - Impermeable to acetyl CoA
What are the sources of acetyl-CoA for fatty acid biosynthesis?
Fatty acid biosynthesis
Glucose
Amino acids
Pyruvate
dehydrogenase
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Elongation and desaturation of fatty acids
Formation of Acyl-CoA is required
before elongation or saturation:
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*Essential
fatty acids
*
*
(ARA)
[Animals and human do not have enzymes to introduce double bonds beyond C-9]
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ARA + CoA-SH thioesterase
Linolenate + CoA-SH
ATP AMP + PPi
[Both the acyl chain and NADH are oxidized by O2]
(condensation)
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Biosynthesis of Triacylglycerols (in cytosol) Fatty acids are stored in adipose tissues as triacylglycerols ~15 kg triacyglcerol in a 70-kg man Excess carbohydrate is converted to triacylglycerols
(in liver and kidney)
(DHAP)
Glycerol-3-phosphate dehydrogenase
NADH
Formation of glycerol backbone:
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(fatty acid)
Acylation of free hydroxyl groups
acyl transferase
acyl transferase
Phosphatic acid phosphatase
(a diacylglycerol-P)
Phospholipid biosynthesis
acyl transferase
Pi
Triacylglycerol
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Sites of regulation of fatty acid metabolism
Triacglycerols - Fuel for energy-requiring
processes - Storage for future use - Synthesis and breakdown
involve different tissues (liver and adipocytes)
Action of hormones - Glucagon increases cAMP levels - Insulin decreases cAMP levels
Malonyl-CoA - Inhibits entry of fatty acyl-CoA
into mitochondria
Long term regulation - Changes in enzyme quantities