28 - Lipid Metabolism I Flashcards
A major source of ________ for fatty acid synthesis is dietary carbohydrates.
Carbon
Where does fatty acid synthesis primarily occur?
Liver
T/F. Fatty acid synthesis can also occur in adipose tissue, brain, kidneys, and lactating mammary glands.
True
Fatty acid synthesis requires coordination between _________ and _________ reactions.
Cytosolic
Mitochondrial
In the end product of FA synthesis, what does each end of the chain consist of?
Carboxyl
Methyl
The precursor of FA synthesis is a 2-carbon molecule such as _________.
Acetyl CoA
There are 3 major steps or phases in the synthesis of fatty acids. Phase I is the cytosolic entry of ________. It is made in the mitochondrial matrix but needed in the cytoplasm.
Acetyl CoA
There are 3 major steps or phases in the synthesis of fatty acids. Phase II is the generation of __________. Acetyl CoA is carboxylated to this, and it is the most important substrate in FA synthesis. Rate limiting reaction.
Malonyl CoA
There are 3 major steps or phases in the synthesis of fatty acids. Phase III is the formation of the…
Fatty acid chain
In Phase III, the enzyme _______ _______ _______ catalyzes 7 reactions that incorporate acetyl CoA and malonyl CoA into ________, a C16 fatty acid.
Fatty acid synthase
Palmitate
Phase I; Step 1 – Condensation of Acetyl CoA with _________ to form _________. Catalyzed by ________ ________.
Oxaloacetate
Citrate
Citrate synthase
Phase I; Step 2 – Transport of citrate from ________ to ________ via a citrate transporter.
Mitochondria
Cytosol
Phase I; Step 3 – Citrate converted back to Acetyl CoA and Oxaloacetate. Catalyzed by _______ _______. The Acetyl CoA is then used for FA synthesis in the cytoplasm.
Citrate lyase
What negatively regulates the conversion of citrate to acetyl CoA and oxaloacetate?
PUFA
Leptin
What positively regulates the conversion of citrate to acetyl CoA and oxaloacetate?
Glucose
Insulin
Phase I; Step 4 – Oxaloacetate is reduced to ________ by ________ _________.
Malate
Malate dehydrogenase
Phase I; Step 5 – Malate is transported into the mitochondria via ________ ________ transporter and oxidized to oxaloacetate by malate dehydrogenase.
Malate alpha-ketoglutarate
Phase I; Step 6 – Cytosolic malate is converted to ________ by _______ ________. It is then transported to the mitochondria via _________ transporter and carboxylated to oxaloacetate by _________ ________.
Pyruvate
Malic enzyme
Pyruvate
Pyruvate carboxylase
Phase II – Acetyl CoA (2 carbon) is converted to _________ (3 carbon) by carboxylation.
Malonyl CoA
Phase II – Acetyl CoA conversion to Malonyl CoA is catalyzed by ________ ________. This is the rate limiting enzyme of the fatty acid biosynthesis pathway.
Acetyl CoA Carboxylase (ACC)
Phase II – ACC adds a _____ to acetyl CoA. It also uses ______ (for energy) and _______ as co-factor.
CO2
ATP
Biotin
Phase II – ACC exists in dimeric (ACTIVE/INACTIVE) forms or polymeric (ACTIVE/INACTIVE) forms.
Inactive
Active
What positively regulates ACC?
Citrate
Insulin
What negatively regulates ACC?
Glucagon Epinephrine High AMP Palmitate PUFA
This is the substrate for Fatty Acid Synthase (FAS).
Malonyl CoA
Malonyl CoA also acts as a regulator by inhibiting _________ _________, which is the rate limiting step in FA degradation.
Carnitine acyltransferase
T/F. Acetyl CoA prevents FA synthesis and degradation from occurring simultaneously.
False. It is Malonyl CoA that does this.
In fatty acid chain formation, two carbon units from malonyl CoA are sequentially added to the growing fatty acyl chain in ______ reactions to form ________ (16:0).
7
Palmitate
The reactions of fatty acid synthesis occur on what?
Fatty Acid Synthase (FAS) Complex
Fatty acid synthase (FAS) is a large multi-enzyme complex. It is composed of 2 identical dimers arranged in head to tail conformation. Each has _____ enzyme activities and an _______ _______ _______ that acts as a flexible arm.
7
Acyl carrier protein (ACP)
This group is present in the ACP and CoA.
Phosphopantetheine group (Pan)
What is the stoichiometry for palmitate synthesis?
1 Acetyl CoA + 7 Malonyl CoA + 14 NADPH + 14 H+ = CH3(CH2)14COO- (palmitate) + 14 NADP+ + 8CoA + 6H2O
On the FAS complex, Acetyl CoA attaches to the _______ and the Malonyl CoA attaches to the ______ or ACP. After this, both CoA are released so they are an Acetyl group (2 carbon) and Malonyl Group (3 carbon).
Cys-SH
Pan-SH
Once the Acetyl group and Malonyl group are attached to Cys-SH and Pan-SH, they undergo a _________ reaction where a CO2 is released (lose a carbon). Now there is a Beta-ketoacyl group (4 carbon) attached to the Pan-SH.
Condensation
The Beta-ketoacyl group undergoes a ________ using NADPH. Now there is a Beta-hydroxyl group attached to the Pan-SH.
Reduction
The Beta-hydroxyl group attached to the Pan-SH then undergoes a __________ reaction and loses H2O. Now there is a trans-enone group attached to the Pan-SH.
Dehydration
Finally, the trans-enone group undergoes another ________ reaction with the use of NADPH. Now there is a 4-carbon fatty acyl group on Pan-SH.
Reduction
Once there is a 4-carbon fatty acyl group on Pan-SH, the group is transferred back to the _______. This opens up the Pan-SH for another malonyl CoA to attach. This reaction is repeated 6 more times until we get palmitate.
Cys-SH
Palmitate is released from the ______ on the FAS complex.
Pan-SH
What are the sources of NADPH for fatty acid synthesis?
Malic enzyme (provides 1) Pentose phosphate pathway (provides 2-12)
In the reactions of fatty acid synthesis, Acetyl ACP and Malonyl ACP condense (lose CO2) to form…
Acetoacetyl ACP
In the reactions of fatty acid synthesis, Acetoacetyl ACP reduces using _______ and forms _____________.
NADPH
D-3-Hydroxbutyryl ACP
In the reactions of fatty acid synthesis, D-3-Hydroxbutyryl ACP dehydrates (loses H2O) and forms…
Crotonyl ACP
In the reactions of fatty acid synthesis, Crotonyl ACP reduces again using _______ and forms __________.
NADPH
Butyryl ACP
1 Acetyl CoA + 1 Malonyl CoA + 2 NADPH = what size acyl group?
4-carbon fatty acyl group
4-carbon fatty acyl group + 1 Malonyl CoA + 2 NADPH = what size acyl group?
6-carbon fatty acyl group
6-carbon fatty acyl group + 1 Malonyl CoA + 2 NADPH = what size acyl group?
8-carbon fatty acyl group
8-carbon fatty acyl group + 1 Malonyl CoA + 2 NADPH = what size acyl group?
10-carbon fatty acyl group
10-carbon fatty acyl group + 1 Malonyl CoA + 2 NADPH = what size acyl group?
12-carbon fatty acyl group
12-carbon fatty acyl group + Malonyl CoA + 2 NADPH = what size acyl group?
14-carbon fatty acyl group
14-carbon fatty acyl group + Malonyl CoA + 2 NADPH = what size acyl group?
16-carbon fatty acyl group
Fatty acid synthesis has multiple points of regulation. Gene expression of the enzymes is induced by a low ______, high _______ diet. It is 25-100 fold more active in a fed state.
Fat
Carb
In phase I, the regulation of ATP citrate lyase is stimulated by __________.
Phosphorylation
In phase I, gene expression of ATP citrate lyase is induced by what?
Glucose
Insulin
In phase I, the induction of gene expression of ATP citrate lyase is inhibited by…
PUFAs (Polyunsaturated fatty acids)
Leptin
Acetyl CoA Carboxylase is the rate limiting step of FA synthesis. As a dimer, it is (ACTIVE/INACTIVE) but as a polymer it is (ACTIVE/INACTIVE).
Inactive
Active
Acetyl CoA Carboxylase can be allosterically regulated. A positive regulation is by _________ and a negative regulation is by ___________ such as palmitate.
Citrate
Long chain fatty acids
Acetyl CoA Carboxylase can also be regulated by phosphorylation which (POSITIVE/NEGATIVE) and dephosphorylation (POSITIVE/NEGATIVE).
Negative
Positive
Acetyl CoA Carboxylase is positively regulated by ________ because of dephosphorylation via activation of _______ _______.
Insulin
Protein phosphatase
Acetyl CoA Carboxylase is negatively regulated by ________ and ________ because of phosphorylation via activation of protein kinase A.
Epinephrine
Glucagon
Acetyl CoA Carboxylase is negatively regulated by _______ because of phosphorylation via activation of AMP kinase (energy sensor).
AMP
Acetyl CoA Carboxylase gene expression is (UP/DOWN)-regulated by high carb/low fat diet.
Up-regulated
In the regulation of fatty acid synthase (FAS), the allosteric effect which is the presence of __________ sugars, will increase activity.
Phosphorylated
In the regulation of FAS, ________ and _________ hormones increase synthesis.
Insulin
Glucocorticoid
In the regulation of FAS, a high carb/low fat diet (DECREASES/INCREASES) synthesis.
Increases
In the regulation of FAS, high fat diets as well as starvation (DECREASES/INCREASES) synthesis.
Decreases
In the regulation of FAS, high _______ suppresses synthesis.
PUFA
In the synthesis of a longer fatty acid chain (longer than palmitate), palmitate is converted and made longer in the _________ or _________.
SER (smooth endoplasmic reticulum)
Mitochondria
________ cells need longer chain fatty acids (C18-24)
Brain
FA is lengthened 2 carbons at a time and NADPH is used as reducing power. SER pathway uses __________ as carbon donor, and mitochondria uses __________ as carbon donor.
Malonyl CoA
Acetyl CoA
Desaturation is the introduction of ______ ______ in FA.
Double bonds
Desaturation occurs in the SER, uses NADPH (or NADH) and oxygen, and is catalyzed by…
Acyl CoA Desaturases
Humans have 4 desaturases, which are…
Delta-4
Delta-5
Delta-6
Delta-9
***This means they can introduce double bonds between carbons 4-5, 5-6, 6-7, and 9-10
T/F. FA with double bond beyond carbon 9 and 10 cannot be synthesized in humans.
True
Examples of FA that have double bonds beyond carbon 9 and 10 are…
Omega 3 fatty acids
Omega 6 fatty acids
FA that have double bonds beyond carbon 9 and 10 need to be ingested or their precursors in diet. The precursors are called…
Essential fatty acids
Humans cannot synthesize omega-3 and omega-6 fatty acids. They need to ingest these via diet or their precursors such as ________ ________ or ________ _________.
Linoleic acid (18:2 omega-6) Linolenic acid (18:3 omega-3)
Linoleic acid (a precursor/essential FA) is used to make ________ ________, which is a precursor for eicosanoids (prostaglandins, leukotrienes, and thromboxanes).
Arachidonic acid (20:4 omega-6)
Linolenic acid (a precursor/essential FA) is used to make __________ _________ and _________ _________.
Eicosapentanoic acid (EPA) (20:5 omega-3) Docosahexanoic acid (DHA) (22:6 omega-3)
Human desaturases cannot introduce unsaturation beyond C9 and the _______ end (omega end).
Methyl
What are the benefits of omega-3 and omega-6 fatty acids?
Immune system Cardiovascular system Nervous system Vision Cell membrane
Fatty acids are incorporated into ___________, which is the storage form of lipids and are stored in adipose tissue. They are used to provide energy.
Triacylglycerols (TAGs)
_________, a 20:4 fatty acid derived from linoleate, is the major precursor of several classes of signal molecules: __________, __________, __________, and _________.
Arachidonate Prostaglandins (PG) Prostacyclins Thromboxanes Leukotrienes
A __________ is a 20-carbon fatty acid containing a 5-carbon ring. This basic structure modified by reductases and isomerases to yield nine major classes of __________, designated PGA through PGI.
Prostaglandins
Prostaglandins
Arachidonate produces prostaglandin, then prostaglandin gives rise to other prostaglandins, _________, and _________.
Prostacyclin
Thromboxanes
PGs and other eicosanoids are local hormones because they are short-lived. They influence the activities of cells producing them and also of neighboring cells by binding to ________. The effects are cell type specific.
GPCRs
PGs stimulate _________, regulate blood flow to particular organs, control ion transport across membranes, modulate synaptic transmission, and induce ________.
Inflammation
Sleep
Clinical example: ________ blocks the enzyme that converts arachidonate into prostaglandin H2. Because arachidonate is the precursor of the other PGs, prostacyclin, and thromboxanes, blocking this step interferes with many signaling pathways (which accounts for its wide-ranging effects on inflammation, fever, pain, and blood clotting).
Aspirin
