Lecture 28 Flashcards
What is the major source or carbon for fatty acid synthesis?
Dietary Carbohydrates
Fatty acid synthesis requires coordination between _____ and ____ reactions
cytosolic
Mitochondrial
Where does fatty acid synthesis occur in the human body? (determine which area is the primary area for this)
Primarily in the liver, but also in adipose tissue (brain, kidneys, lactating mammary glands
What is the precursor for FA synthesis? how many carbons are in this precursor and compare that the the number of carbons in the FAs it is used to create
Acetyl-CoA, which is a 2 carbon molecule
FAs have many more carbons
State the 3 phases of FA synthesis and include the locations within the cell where these steps occur
Phase I: Cytosolic entry of Acetyl CoA
Made in mito matrix (but is needed in the cytoplasm)
Phase II: Generation of Malonyl CoA
Occurs in cytoplasm
Phase III: FA chain formation
Occurs in cytoplasm
What is the rate limiting step of FA synthesis?
Generation of Malonyl CoA from Acetyl CoA
What enzyme catalyzes the 7 reactions that must occur to carry out phase III of FA synthesis
FA synthase incorporates Acetyl CoA and Malonyl CoA into larger FA molecules
State the 2 enzymes that are used to make Acetyl CoA in order to carry out phase I of FA synthesis (one in mito and one in cytoplasm) and state the metabolic pathway each enzyme is associated with
Citrate Synthase: part of the TCA cycle that occurs in the mito
ATP citrate lyase: part of glycolysis that occurs in the cytoplasm
(Basically opposites of each other)
Describe the 6 steps that occur during phase I (cytosolic entry of Acetyl CoA) of FA synthesis
- Citrate synthase catalyzes condensation of Acetyl CoA with Oxaloacetate (OAA) to from citrate
- Citrate Transporter moves Citrate from mito to cytosol
- Citrate Lyase converts Citrate BACK into Acetyl CoA and OAA
- Malate dehydrogenase reduces OAA to Malate (Acetyl CoA is used to synthesize FAs)
- Malate-alpha ketoglutarate transporter moves malate into the mito where it is oxidized BACK to OAA by “Malate dehydrogenase”
- Malic enzyme converts cytosolic malate into pyruvate.
A Pyruvate transporter then moves pyruvate into the mito where “pyruvate carboxylase” carboxylates it to OAA
State the rate limiting enzyme of FA synthesis, include the phase of FA synthesis this enzyme is involved in, and describe the reaction that occurs (include other substances that are necessary)
Acetyl CoA Carboxylase (ACC) is the rate limiting enzyme of FA synthesis and it is involved in Phase II
ACC adds CO2 to Acetyl CoA (2 carbon molecule) to form Malonyl CoA (3 carbon molecule)
Biotin is a cofactor for the ACC reaction and ATP is needed to supply energy
ACC exists in dimeric (___) or polymeric (_____) forms. (active or inactive)
Dimeric (inactive)
Polymeric (active)
Malonyl CoA prevents FA _____ and _____ from occurring simultaneously. Malonyl acts as both a Substrate and a Regulator. explain this.
synthesis
degradation
Malonyl CoA is a substrate for FAS (FA synthase)
Malonyl CoA acts as a regulator by inhibiting carnitine acyltransferase (rate limiting step in FA degradation)
Describe the function of the FAS complex and what is ultimately formed
FA synthesis reactions occur in the FAS complex
Malonyl CoA (2 carbons) molecules are added into a growing FA chain 7 TIMES in order to form Palmitate (16 carbons)
(7 reactions happening here makes sense bc 2+(7*2) = 16)
Describe the structure of the FAS complex, the arrangement of it’s components
FAS is a multi-enzyme complex composed of 2 identical dimers
The Dimers are arranged in a “head to tail” conformation
For the FAS complex, state the 2 characteristics it uses for adding Malonyl CoA subunits together to form FA chains. Describe how these interact.
- 7 enzymes (each with their own reactions)
- Acyl Carrier Protein (ACP)
Has a flexible arm that facilitates the delivery of the substrate between the 7 enzymes
What is the “phosphopantetheine group”?
Phosphopantetheine group: the end of the ACP “arm” that grabs onto the substrate
State the Stoichiometric reaction for the synthesis of palmitate (you can omit the hydrogens but include NADPH)
1 Acetyl CoA + 7 Malonyl CoA + 14 NADPH = 1 Palmitate + 8 CoA + 14 NADP+
Compare the functions of the Cys-SH and Pan-SH parts of FAS when it comes to making FAs
once the initial step of Acetyl CoA + Malonyl CoA yields a 4 carbon molecule, the longer chain of carbons attaches to the Cys-SH portion of FAS while the incoming Malonyl CoA is loaded onto the Pan-SH portion of FAS
Describe the following reactions catalyzed by FAS
Condensation:
Reduction:
Dehydration:
Reduction:
Condensation: The Acetyl CoA and Malonyl CoA forming the initial bond
Releases ACP + CO2
Reduction: reduces one of the =O groups (turns beta-ketoacyl group to beta-hydroxyl group)
Consumes NADPH
Dehydration: water is lost (forms trans-enone group)
Reduction: reduces a C=C bond to form the 4 carbon molecule that all other Malonyl CoAs will be added to
Consumes NADPH
State the 2 sources of NADPH that are used in the synthesis of Palmitate
Malic enzyme: 1
Pentose Phosphate Pathway: 2-12
NADPH to NADP+ is a _______ reaction, whereas NADP+ to NADPH is a ______ reaction.
Oxidation (Reduction for whatever is receiving the electrons)
Reduction (Oxidation for whatever is losing the electrons)
State the enzyme that represents the regulation point for all 3 phases of FA synthesis.
Phase I: ATP Citrate lyase
Phase II: Acetyl CoA Carboxylase (rate limiting step)
Phase III: FAS
ATP citrate Lyase is ____ by phosphorylation. Also state the molecules that induce gene expression of ATP Citrate Lyase and the 2 things that counteract this gene expression.
Stimulated
Gene expression is induced by Glucose and Insulin
Gene expression is countacted by PUFAs (polyunsaturated FAs) and Leptin
For ACC activity, state the 2 allosteric regulations and the dietary choice that induces an up regulation of it’s gene expression
Allosteric:
Citrate (+)
Long Chain Fatty Acids ex. Palmitate (-)
Induction:
High carb/low fat diet causes an upregulation in the ACC gene
