Please enable JavaScript.
Coggle requires JavaScript to display documents.
CHAPTER 21 Lipid Biosynthesis - Coggle Diagram
CHAPTER 21
Lipid Biosynthesis
基本知識
Functions
Energy storage
Constituents of membranes
Anchors for membrane proteins
Cofactors for enzymes
Signaling molecules
Pigments
Detergents
Transporters
Antioxidants
Catabolism and Anabolism of Fatty Acids
Proceed via Different Pathways
Catabolism of fatty acids
produces acetyl-CoA
produces reducing power (NADH, FADH2)
takes place in the mitochondria
Anabolism of fatty acids
requires acetyl-CoA and malonyl-CoA
requires reducing power from NADPH
takes place in cytosol in animals, chloroplast in plants
Fatty Acid Synthesis
The Acetyl-CoA Carboxylase Reaction
Pathways for NADPH Production
Synthesis of Fatty Acids Is Catalyzed
by Fatty Acid Synthase (FAS)
Catalyzes a repeating four-step sequence that elongates the fatty acyl chain by two carbons at each step
– uses NADPH as as the electron donor
– uses two enzyme-bound -SH groups as activating groups
FAS I in vertebrates and fungi
FAS II in plants and bacteria
The General Four-Step Fatty Acid Synthase I
Reaction in Mammals
Prep: Malonyl CoA and acetyl CoA (or longer fatty acyl chain) are bound to FAS I and lose CoA.
bind via thioester terminus or a Cys of the FAS
activates the acyl group
Step 1: Condensation reaction attaches two C from acetyl group (or longer fatty acyl chain) to two C from malonyl group.
release of CO2 activates malonyl group for attachment
creates β-keto intermediate
Fatty Acid Synthesis
Overall goal: attach acetate unit (2-carbon) from malonyl-CoA to a growing chain and then reduce it
Reaction involves cycles of four enzyme-catalyzed steps:
– condensation of the growing chain with activated acetate
– reduction of carbonyl to hydroxyl
– dehydration of alcohol to trans-alkene
– reduction of alkene to alkane
The growing chain is initially attached to the enzyme via a thioester linkage
Fatty Acid Synthesis Occurs in Cell Compartments
Where NADPH Levels Are High
Cytosol for animals, yeast
Chloroplast for plants
Sources of NADPH:
– in adipocytes: pentose phosphate pathway and malic enzyme.
NADPH made as malate converts to pyruvate + CO2.
– in hepatocytes and mammary gland: pentose phosphate pathway.
NADPH made as glucose-6-phosphate converts to ribulose 6-phosphate.
– in plants: photosynthesis
Step 1 of FAS I: Elongation
Overview
Fatty acids are built in several passes, processing one acetate unit at a time.
The acetate is coming from activated malonate in the form of malonyl-CoA.
Each pass involves reduction of a carbonyl carbon to a methylene carbon.
Fatty Acid Synthesis in Detail:
Condensation and Elongation
Activated acetyl and malonyl groups form acetoacetyl-ACP and CO2.
– Claisen condensation reaction
Catalyzed by β-ketoacyl-ACP synthase
Coupling condensation to decarboxylation of malonyl-CoA makes the reaction energetically favorable.
Malonyl-CoA Is Formed from
Acetyl-CoA and Bicarbonate
Reaction carboxylates acetyl-CoA
Catalyzed by acetyl-CoA carboxylase
The enzyme has three subunits:
One unit has biotin covalently linked to Lys.
Biotin carries CO2
In animals, all three subunits are on one polypeptide chain.
HCO3− (bicarbonate) is the soluble source of CO2.
Steps 2−4 of the FAS I Rx
ACP
Acyl Carrier Protein (ACP) Serves
as a Shuttle in Fatty Acid Synthesis
Contains a covalently attached prosthetic group 4’-phosphopantetheine
– flexible arm to tether acyl chain while carrying intermediates from one enzyme subunit to the next
Delivers acetate (in the first step) or malonate (in all the next steps) to the fatty acid synthase
Shuttles the growing chain from one active site to another during the four-step reaction
Charging ACP and FAS I with
Acyl Groups Activates Them
Two thiols must be charged with the correct acyl groups before the condensation reaction can begin.
– thiol from 4-phosphopantethine in ACP
– thiol from Cys in fatty acid synthase
The acetyl group of acetyl-CoA
is transferred to ACP.
– catalyzed by malonyl/aceyl-CoA transferase (MAT)
– ACP passes this acetate to the Cys of the β-ketoacyl-ACP synthase (KS) domain of FAS 1.
– ACP –SH group is recharged with malonyl from malonyl-CoA.