Fatty Acid Metabolism 2 - Degradation Flashcards
When TAGs are ingested in the diet, bile acids and H2O along with what enzyme are responsible for breaking them down in the intestines so that they can cross the lipid bilayer?
Pancreatic lipases break TAGs into fatty acids and monoacylglycerols
After pancreatic lipases break TAGs down into fatty acids and monoacylglyerols which cross the cell membrane, they reassemble into TAGs and combine with ______________ to form chylomicrons, which are transported via the lymph system to the blood
Apolipoproteins (Apo-B48)
Prior to beta oxidation, fatty acids must be “activated”, where does this occur?
In the cytosol
Where does beta-oxidation of FA’s occur?
In the mitochondrial matrix of hepatocytes
Cleavage of FAs happens 2-carbons at a time, what is the yield after each cleavage?
Ac-CoA
FADH2
NADH
Short chain fatty acids and medium chain fatty acids can diffuse into the mitochondria. How do long chain fatty acids and very long chain fatty acids get into the mitochondria?
They need to be actively transported, which consists of oxidation in peroxisomes to form LCFAs which are transported via the carnitine shuttle
This enzyme activates LCFAs using ATP and forms a thioester bond between FAs and CoA. It is located on the outer mitochondrial membrane, but the reaction catalyzed is on the inner (cytoplasmic side)of the membrane
Fatty acyl CoA synthetase
What enzyme is responsible for transferring Fatty Acyl from Fa-CoA to Carnitine to form FA-carnitine and is located in the intermembrane space?
Carnitine palmitoyltransferase I (CPT1)
What is the rate limiting enzyme in beta oxidation?
CPT1 (carnitine palmitoyltransferase I aka carnitine acyltransferase)
What enzyme is responsible for moving FA-carnitine into the intermembrane space?
Carnitine-acylcarnitine translocase
[operates as an antiporter: FA-carnitine in – Carnitine out]
What enzyme is responsible for forming FA-CoA from FA-carnitine once it reaches the mitochondrial matrix?
Carnitine palmitoyltransferase II (CPTII)
What are the sources and total yield of ATP for one round of beta oxidation?
FADH2 = 2 ATPs
NADH = 3 ATPs
Acetyl CoA = 12 ATPs
Total = 17 per round
The first step of beta oxidation occurs through the action of acyl CoA dehydrogenase. What is the most common deficiency associated with this step?
MCAD
The process of beta oxidation on a FA with an odd number of carbons is similar to even-numbered FAs until it is 3-carbons long, aka ________________
Propionyl CoA
Once an odd-numbered FA is metabolized down to propionyl CoA, a carboxylase utilizes ATP to add CO2 to methylmalonyl-CoA, which then acted on by a mutase to generate ______________ which can then enter the TCA cycle
Succinyl CoA
Describe the beta oxidation process of unsaturated fatty acids (what 2 enzymes are required?)
Metabolism proceeds until point of unsaturation is reached (double bond)
At that point, reductase removes the double bond and isomerase moves it
True or false: Beta-oxidation in peroxisomes produces ATP
False; it does not produce any ATP, but it generates high potential electrons that are transferred to O2, producing hydrogen peroxide. Catalase reduces this because it would otherwise be toxic
Peroxisomal beta-oxidation is slightly different in that the first step is catalyzed by _______ __________. NADH formed in the 3rd oxidative step cannot be re-oxidized in the peroxisome; reducing equivalents are exported to the cytosol. Peroxisomal carnitine acyltransferase is used for transport, and peroxisomal beta-ketothiolase has altered substrate specificity
Acyl-coA oxidase
What deficiency impairs the body’s ability to break down medium-chain fatty acids into acetyl CoA and would result in hypoglycemia/sudden death without timely intervention?
MCAD deficiency
What is the primary method of treatment for MCAD deficiency?
Avoid fasting and other situations where the body would rely on FA-Beta oxidation to supply energy
Ketone bodies consist of water-soluble and acidic compounds - there are 3 main ketone bodies, what are they?
Acetoacetate
Beta-hydroxybutyrate
Acetone
True or false: ketone bodies are produced in the liver, kidneys, and brain
FALSE, they are produced in the liver only. Synthesis of ketone bodies occurs in the mitochondrial matrix of hepatocytes
A low carb diet is likely to be hard on which of the following?
A. Brain
B. Muscle
C. Kidneys
D. Red blood cells
D. Red blood cells
Ketone bodies are utilized by the brain, muscle, and kidneys.
What is the typical energy yield from ketone bodies like acetate and beta-hydroxybutyrate?
One acetate yields 23 ATP
One beta-hydroxybutyrate yields 26 ATP
The 2 main ketone bodies are acetoacetate and beta-hydroxybutyrate. Their interconversion is catalyzed by what enzyme?
Mitochondrial beta-hydroxybutyrate dehydrogenase
A ________ NADH:NAD+ ratio inhibits the TCA cycle and diverts acetyl CoA toward ketone body synthesis
High
