Chapter 16 Fatty Acid Catabolism Flashcards
(X:Y) delta 1,2,3
What does this naming system of fatty acids mean?
X is the number of carbons in the fatty acid
Y is the number of double bonds
delta marks the positions of the double bond.
What is the omega naming system for fatty acids?
Omega is the terminal carbon, the number represents the position of the first double bond.
Omega-3
the first double bond is on position three
As the number of carbons in the hydrophobic chain increases the melting temperature _____________.
Increases
As the number of unsaturations increases the melting temperature ______________________.
Decreases
Why do unsaturations decrease melting temperature?
bent and kinked fatty acids are less well packed together and so have greater mobility.
Require less energy (low temp) to transition from solid to more fluid state.
What human organ obtains most of its energy needs from fatty acids?
Heart
Name four sources of fatty acids for catabolism
- ingested fats
- fats stored in adipocytes (fat cells)
- fatty acids synthesized within the body
- fatty acids recycled from autophagy
What are adipocytes?
cells that store triacylglycerols and cholesterol
What are adipokines?
signaling molecules synthesized by adipocytes that regulate hunger and metabolism.
What are leptins?
inhibits hunger
What is adiponectin?
regulates glucose levels and fatty acid catabolism
What is autophagy?
Process whereby a cell degrades damaged or non-functional components.
Describe the set of reactions resulting in the transport of ingested fats into the blood and then taken up by the tissues?
- bile salts emulsify dietary fats in the small intestine forming mixed micelles.
- triacylglycerols degraded
- Fatty acids are taken up and converted into triacylglycerols.
- Triacylglycerols are incorporated with cholesterol and apolipoproteins into chylomicrons.
- Chylomicron move through the lymphatic system and bloodstream to tissues.
- A lipase converts triacylglycerols back to fatty acids and glycerol.
- Fatty acids enter cells
- Fatty acids are oxidized as fuel or saved for storage.
What is the function of bile salts?
emulsify ingested fats to break up large fat globules.
What are chylomicrons?
carry fatty acid from liver to tissue via lymphatic and blood circulatory system.
What are lipoprotein particles?
transport lipids such as cholesterol and triglycerides through the bloodstream
What are apolipoproteins?
bind to lipids forming lipoprotein particles.
Name functions of apolipoproteins
make lipids more soluble
are recognized by cell surface receptor proteins
What are perilipins?
act like a coating or a shell on the surface of the lipid droplet preventing lipases from accessing triacylglycerols unless they are needed.
How is the assembly of perilipins on the surface of lipid droplets regulated?
Low glucose ā-> secretion of glucagon
Glucagon activates a GPCR that undergoes a conformational change and activates Galpha-s
Galpha-s activates adenylate cyclase which synthesizes cAMP. cAMP activates protein kinase A.
Protein kinase A phosphorylates the perilipin causing the perilipin to change orientation making triacylglycerols more accessible to lipases.
Three lipases cleave fatty acids off of glycerol.
What is ATGL?
adipose triacylglycerol lipase, cleaves triacylglycerols to diacylglycerols.
What is HSL?
hormone sensitive lipase, cleaves diacylglycerol to monoacylglycerol.
What is MAG lipase?
monoacylglycerol lipase, cleaves monoacylglycerol to a fatty acid and glycerol.
Explain activation mechanism of ATGL.
Regulated by CA protein and perilipins
when perilipin is phosphorylated they release the CA protein which can then fully activate ATGL.
Explain activation mechanism of HSL.
HSL is regulated by GPCR/Galpha-s pathway, activation of protein kinase A phosphorylates HSL turning it on.
Is MAG ligase regulated?
No
How is energy recovered form the glycerol portion of the triacylglycerols?
liver takes up the free glycerol and converts it to D-glyceraldehyde-3-phosphate.
The D-glyceraldehyde-3-phosphate can then enter glycolysis or gluconeogenesis based on metabolic need.
Write out the reactions of recovering energy from the glycerol portion of the triacylglycerols
refer to slides
What did Knoop discover that revealed the fundamental basis of fatty acid oxidation?
all fatty acids with even numbers of carbons produced phenylacetic acid as a final product.
all fatty acids with odd numbers of carbons produced benzoic acid as the final product.
FATTY ACID OXIDATION- THE CHAIN WAS SHORTENED IN STEPS OF 2 CARBONS.
What is the distinction between long chain and short chain fatty acids in how they enter the mitochondria?
fatty acids with 12 or fewer carbons: can enter the mitochondria directly.
fatty acids with 14 or more carbons: enter the mitochondria through the carnitine shuttle.
Write out the steps for fatty acid activation
refer to slides
- fatty acids carries out nucleophilic attack on first phosphate of ATP. PPi leaves
- CoA-SH attacks fatty acyl adenylate. AMP leaves, fatty acyl coA forms.
What reaction and enzyme drives the fatty acyl coA synthesis reaction forward?
the enzyme inorganic pyrophosphatase helps drive this reaction in the forward direction by cleaving the PPi to Pi.
What are the two fates of fatty acyl coA?
- synthesis of membrane lipids (cytosol)
- oxidation to acetyl-coA (mitochondria)
What are the reaction steps of the carnitine shuttle?
- attachment of fatty acid to carnitine catalyzed by carnitine acyl transferase I enzyme
- carnitine fatty acid moves across outer membrane and enters into matrix in the inner mitochondrial membrane.
- Liberation of free fatty acid, accomplished by carnitine acyltransferase II.
What is beta oxidation?
the sequential removal of 2C from each fatty acid to produce acetyl coA.
What is the process of recovering energy from fatty acids?
- fatty acid is broken down into units of 2 C (acetyl-coA)
- acetyl-coA enters citric acid cycle, electrons are abstracted for use in ETC.
- Reduced electron carriers release their electrons into ETC which is used to create a proton gradient for ATP synthesis.
Contrast the chemical stability and oxidation of a representative carbon in a fatty acid and glucose.
most glucose carbon atoms are in proximity to a carbonyl group and have C-O bonds.
The tails of fatty acids chains are chemically inert.
What are the steps of beta oxidation?
refer to slides
Is the double bond introduced during beta oxidation cis or trans?
Trans
How many NADH and FADH2 are generated in beta oxidation of saturated fatty acid?
1 NADH per beta oxidation
1 FADH2 per beta oxidation
How many rounds of beta oxidation are required to completely break down ānā number of carbon saturated fatty acids?
[(n)/2] -1
What step of the beta oxidation process resembles a step in the citric acid cycle?
the step of converting the double bond into alcohol and CH2 resembles fumarase reaction of citric acid cycle.
What are the potential challenges of performing beta oxidation on a monounsaturated fatty acid?
the double bonds are usually cis and have to made into a trans double bond by an isomerase.
Why is less energy obtained from the oxidation of a monounsaturated fatty acid group than the saturated fatty acid of the same length?
skipped the first step introduction of the double bond which transferred a pair of electrons to the ETC.
Write out mechanism of beta oxidation of monounsaturated fatty acid
refer to slides
How many NADH and FADH2 are produced for beta oxidation of monounsaturated fatty acid?
One fewer FADH2 because when we reach the cis double bond we have to skip the first step and go through the isomerase step.
How is mechanism for monounsaturated fatty acid different than saturated fatty acid?
The monounsaturated we continue as normal until we reach cis double bond which we convert to trans double bond using isomerase.
How is the mechanism different for polyunsaturated fatty acids?
the steps are the same but when we reach the part where two double bonds are next to each other we use NADPH to reduce one of the double bonds in order to be able to move the position of the other double bond through isomerase.
What does the last round of beta oxidation of even numbered fatty acids produce?
2 carbon acetyl coA molecules.
What does the last round of beta oxidation of odd numbered fatty acids produce?
one acetyl-coA and one three carbon fatty thioacyl compound propionyl coA.
What are the three steps required to metabolize propionyl coA?
- ATP activates bicarbonate, COO- attached to propionyl coA.
- Inversion of stereochemistry to give L-methyl malonyl coA.
- Methyl malonyl coA gives succinyl coA by a reaction catalyzed through the Vitamin B12 cofactor.
What is unusual about the mechanism of Vitamin B12 reactions?
hydrogen atom on the methyl carbon is switching positions with succinyl coA.
Write out the methyl malonyl mutase mechanism.
Refer to slides
What are three ketone bodies?
acetone, aecetoacetate, and 2-hydroxybutyric acid
When are ketone bodies synthesized?
during periods of glucose starvation
oxaloacetate is being diverted to gluconeogenesis which results in accumulation of acetyl-coA that converts into ketone bodies.
Write out the full pathway for ketone body synthesis
Where are ketone bodies generated?
In the liver
How many acetyl-coA molecules are required for the synthesis of a ketone body?
2 acetyl-coA
How many acetyl-coA appear in the final ketone body?
zero
Write out the pathway for the conversion of ketone bodies from beta-hydroxybutyrate to acetyl-coA
beta-hydroxybutyrate
acetoacetate
acetoacetyl coA
2 acetyl coA
What is the first coA donor for the formation of acetyl-coA in the beta-hydroxybutyrate pathway?
succinyl coA
Of the three ketone bodies, which is not used for fuel by the body?
acetone
