Lipid Metabolism Flashcards
Units of what carbon length are added to a growing hydrocarbon chain?
2-carbon units
Main substrate for fatty acid biosynthesis
Malonyl-ACP (ACP=acyl carrier protein)
Carboxylated analog of acetyl CoA bound to ACP
Synthesis of malonyl-ACP
- Carboxylation of acetyl CoA (catalyzed by acetyl-CoA carboxylase bound to biotin)
- Transacylation from CoA to ACP
Initiation of fatty acid synthesis
Acetoacetyl-ACP (also referred to as 3-ketoacyl ACP) is synthesized from acetyl CoA and malonyl ACP (catalyzed by 3-ketoacyl ACP synthase)
“Newest” 2-carbon unit is closest to what in the growing chain?
ACP
Reaction #1 of fatty acid elongation
Reduction of a ketone to a secondary alcohol
3-ketoacyl ACP -> D-3-hydroxyacyl ACP
Enzyme: 3-ketoacyl-ACP reductase
Reaction #2 of fatty acid elongation
Dehydration of a secondary alcohol to a trans-alkene
D-3-hydroxyacyl ACP -> trans-delta2-enoyl ACP
Enzyme: 3-hydroxyacyl-ACP dehydratase
Reaction #3 of fatty acid elongation
Reduction of a trans-alkene to an alkane
Trans-delta2-enoyl ACP -> acyl ACP
Enzyme: enoyl-ACP reductase
End product of fatty acid synthesis
16- and 18-carbon saturated fatty acids
Active site cannot tolerate longer chains
Termination of fatty acid synthesis
Palmitoyl ACP is hydrolyzed by thioesterase to form palmitate (C 16) + HS-ACP
Net reaction for synthesis of palmitate (C 16)
Acetyl CoA + 7 malonyl CoA + 14 NADPH + 14 H+ -> palmitate + 7 CO2 + 14 NADP+ + 8 HS-CoA + 6 H2O
Elongases
Enzymes that use malonyl CoA to extend fatty acid chains
Desaturases
Enzymes that introduce unsaturations into fatty acid chains
Polyunsaturated fatty acids usually have their unsaturations introduced every how many carbons?
Every 3 carbons
Desaturase mechanism
Molecular O2 is used as oxidant to oxidize single bond to double bond
NADH is oxidized to NAD+ (2 electrons) and O2 is reduced to 2 H2O (4 electrons)
Elongase mechanism
Malonyl CoA is added onto beginning of fatty acid chain
How fatty acids are typically stored
Triacylglycerols
Step 1 of triacylglycerol synthesis
Glycerol 3-phosphate + acyl CoA -> 1-acylglycerol-3-phosphate (carbonyl carbon attached to -OH of C1)
Enzyme: glycerol 3-phosphate acyltransferase
Step 2 of triacylglycerol synthesis
1-acylglycerol-3-phosphate + acyl CoA -> phosphatidate (carbonyl carbon attached to -OH of C2)
Enzyme: 1-acylglycerol-3-phosphate acyltransferase
Step 3 of triacylglycerol synthesis
Phosphatidate -> 1,2-diacylglycerol (-PO3 of C3 is replaced with -OH)
Enzyme: Phosphatidate phosphatase
Step 4 of triacylglycerol synthesis
1,2-diacylglycerol + acyl CoA -> triacylglycerol (carbonyl carbon attached to -OH of C3)
Enzyme: diacylglycerol acyltransferase
Eicosanoids are derived from what?
Arachidonic acid (20:4 delta 5,8,11,14)
3 stages of biosynthesis of cholesterol
- Acetyl CoA (2C) to isopentenyl diphosphate (5C)
- Isopentenyl diphosphate (5C) to squalene (30C)
- Squalene (30C) to cholesterol (27C)
Key regulatory step in synthesis of isopentenyl diphosphate from acetyl CoA
3-hydroxy-3-methylglutaryl CoA (HMG CoA) -> mevalonate
Reduction of thioester to primary alcohol
Enzyme: HMG-CoA reductase
