Chapter 28: Fatty Acid Synthesis Flashcards
Most of our need for fats and lipids are met by our…
Diet
Fatty acid synthesis occurs in the…
Cytosol
When glucose is abundant, a large amount of _____ is produced that can be used for FA synthesis in cytosol.
Acetyl CoA
The first of 3 stages of FA synthesis is:
The transfer of acetyl CoA out of the mitochondria into the cytoplasm
The second of 3 stages of FA synthesis is:
The activation of acetyl CoA to form malonyl CoA
The third of 3 stages of FA sythesis is:
The repetitive addition and reduction of two carbon units
Citrate, synthesized in the _____, is transported to the _____ and cleaved by _____ to generate acetyl CoA for FA synthesis.
Synthesized in mitochondria and transported to the cytoplasm and cleaved by ATP-citrate lyase
FA Synthesis requires reducing power in the form of…
NADPH
Some NADPH is formed from the oxidation of _____ to _____.
Oxaloacetate to Pyruvate
Additional NADPH comes from _____.
Pentose Phosphate Pathway
The formation of _____ is the committed step in FA synthesis.
Malonyl CoA
Malonyl CoA is synthesized by _____, a biotin-requiring enzyme.
Acetyl CoA carboxylase
What catalyzes the irreversible rate-limiting step of FA synthesis?
Acetyl CoA carboxylase
What catalyzes the formation of fatty acids?
Fatty acid synthase
FA synthesis occurs on the _____, a polypeptide link to CoA.
Acyl carrier protein (ACP)
What attaches substrates to the ACP?
Transacylases
FA Synthesis consists of a series of reactions. What are they?
Condensation, reduction, dehydration and reduction
What catalyzes the condensation of acetyl ACP and malonyl ACP to form acetoacetyl ACP?
B-ketoacyl synthase
The next 3 steps convert the keto group at carbon 3 to a methylene group, forming _____.
Butyryl ACP
_____ are consumed as reducing power.
2 NADPH
Acetyl ACP to Malonyl ACP (required) convert to what via a condensation reaction?
Acetoacetyl ACP
Acetoacetyl ACP converts to _____ via a reduction reaction.
D-3-hydroxbutyryl ACP
D-3-Hydroxbutyryl ACP converts to _____ via a dehydration reaction.
Crotonyl ACP
Crotonyl ACP converts to _____ via a reduction reaction.
Butyryl ACP
Elongation of FA Chain proceeds by addition of 2 carbons from _____.
Malonyl ACP
The second round of synthesis begins with the condensation of _____ with the newly synthesized _____, forming _____.
Condensation of malonyl CoA with butyryl ACP, forming C6-beta-ketoacyl ACP
The reduction, dehydration, reduction sequence is _____.
Repeated
Synthesis continues until _____, which is cleaved by thioesterase to yield _____.
C16-acyl ACP to yield palmitate
The synthesis of palmitate requires?
- 8 Acetyl CoA
- 14 NADPH
- 7 ATP
Mammalian FA synthase is composed of one large single polypeptide chain that consists of 2 compartments:
- Selecting and condensing compartment - condenses the acetyl and malonyl substrates
- Modification compartment - carries out the reduction and dehydration activities required for elongation
Tumors require large amounts of _____ to produce precursors for membrane synthesis.
Fatty acid synthase
Fatty acid synthase inhibitors…
Slow tumor growth
Mice treated with fatty acid synthase inhibitors also showed dramatic _____ and may be used to treat _____.
Weight loss; obesity
Fatty acid synthase cannot generate fatty acids longer than _____.
C16 Palmitate
In order to have longer fatty acids, they must be synthesized by _____.
Enzymes attached to the endoplasmic reticulum
The enzymes that elongate fatty acids extend palmitate by _____, using _____ as a substrate.
Adding two carbon units, using malonyl CoA
Membrane-bound enzymes generate _____.
Unsaturated fatty acids
_____ cannot introduce double bonds during FA synthesis.
Eukaryotes
What introduce double bonds into saturated FAs?
Enzymes bound to the endoplasmic reticulum
Mammals lack the enzymes that introduce double bonds beyond _____.
Carbon 9
What are the two essential fatty acids that must be obtained from the diet?
Linoleate (C18:2) and Linolenate (C18:3)
What is a key regulator of Fatty Acid Metabolism?
Acetyl CoA Carboxylase
There are 3 mechanisms of regulation of fatty acid metabolism. With Acetyl CoA Carboxylase being the key regulator, what is it inhibited by?
- AMPK
- Glucagon
- Epinephrine
- Palmitoyl CoA
There are 3 mechanisms of regulation of fatty acid metabolism. With Acetyl CoA Carboxylase being the key regulator, what is it stimulated by?
- Protein phosphatase 2A (PP2A)
- Citrate
- Insulin
How does Glucagon and Epinephrine affect Acetyl CoA Carboxylase? Insulin?
Glucagon and epinephrine inhibit carboxylase by enhancing AMPK activity.
Insulin activates the carboxylase by causing its dephosphorylation.
Excess ethanol consumption can cause _____.
Liver damage
Ethanol cannot be excreted, it must be…
Metabolized in the liver
One pathway for ethanol processing consists of two steps and leads to _____.
Excess production of NADH
Excess NADH inhibits _____. This results in _____.
- Inhibits gluconeogenesis
- Results in: Hypoglycemia
Excess NADH inhibits _____ and stimulates _____, leading to accumulation of fats in liver, known as _____.
- Inhibits fatty acid degradation
- Stimulates fatty acid synthesis
- Results in: fatty liver
Fatty Acid Synthesis committed step:
Acetyl CoA carboxylase
Fatty Acid Degradation committed step:
Carnitine acyltransferase I
FA Degradation inhibited by _____.
Malonyl CoA
Liver converts some of the acetate to acetyl CoA, which cannot be processed by _____ due to inhibition by _____.
Citric acid cycle due to inhibition of NADH
The build-up of acetyl CoA can lead to _____ by the liver, which exacerbates the _____.
Ketone body secretion which exacerbates the lactic acidosis
If acetate cannot be processed, _____ accumulates.
Acetaldehyde
Acetaldehyde is very reactive and modifies reactive groups of proteins, causing _____.
A loss of protein function
As protein damage accumulates,
Liver function can fail
3 Stages of liver damage by excess ethanol consumption:
- Fatty liver (Liver can be 2X the normal size)
- Alcoholic hepatitis
- Cirrhosis (More shrunken liver)
Chronic ethanol ingestion alters carbohydrate metabolism and leads to a fatty liver due primarily to an increase in which of the following?
- NADH
- NADPH
- ATP
- ADP
- None of the above
NADH
Phospholipid synthesis does NOT require:
Sphinogsine
Tay-Sachs disease is caused by an inability to degrade:
Gangliosides
Fatty acid synthesis occurs in…
Occurs in the cytosol in all species
. The rate limiting step for fatty acid synthesis is promoted by:
Acetyl CoA carboxylase
During the chain elongation step of fatty acid synthesis, the newly added carbons come directly from:
Malonyl ACP
T or F: Acetyl CoA carboxylase is found exclusively in the mitochondria.
False
High concentrations of acetyl CoA in the mitochondria:
Lead to increased transport of citrate from the mitochondria to the cytosol
T or F: High levels of insulin stimulate acetyl CoA carboxylase.
True
T or F: Acetyl CoA carboxylase produces malonyl CoA.
True
T or F: Acetyl CoA carboxylase catalyzes the rate-limiting step for fatty acid synthesis.
True
T or F: Acetyl CoA carboxylase is regulated by phosphorylation and allosteric modification.
True
Fatty acids are elongated and desaturated by…
Enzymes attached to the ER
Excess NADH enhances _____. This results in _____.
- Enhances lactate production
- Results in: Lactic Acidosis
Fatty acid oxidation is increased by:
- Low insulin levels
- Low carbohydrate levels
- High epinephrine levels
- High glucagon levels
All are correct
Fatty acid oxidation…
Requires activation of fatty acids to the CoA form
What is the purpose of the carnitine shuttle system?
To transport fatty acids from the cytosol to the mitochondrial matrix
T or F about fatty acids in mammals:
Double bonds are added during the synthesis of fatty acids
False
T or F: About fatty acids in mammals:
Fatty acids in triacylglycerols provide only limited energy storage
False
T or F: about fatty acids in mammals:
Elongases must be used to synthesize fatty acids longer than 18 carbons
True
T or F: about fatty acids in mammals:
Mammals can synthesize all the fatty acids they need
False
T or F about fatty acids in mammals:
Fatty acids are rarely made in mammals
False
Which statement comparing fatty acid synthesis to fatty acid degradation is TRUE about both processes?
- They both occur in the cytosol
- They both utilize intermediates covalently attached to ACP
- They both can be regulated by insulin levels
- They both require reduction steps
- They both generate energy
They both can be regulated by insulin levels
The building block for triacylglycerol synthesis is:
Glycerol 3-phosphate