Fatty Acid Oxidation and Ketone Bodies. Flashcards
What provides the necessary energy for gluconeogenesis?
Beta oxidation of fatty acids.
Fatty acid oxidation is carried out when the body is in what state?
The fasting state.
What will the beta oxidation of fats provide that can be used as a gluconeogenic regulator?
NADH.
What do high levels of NADH inhibit?
The PDH step and the TCA cycle of glucose metabolism.
How can the NADH and FADH2 that are made in fatty acid oxidation be used to generate energy?
They can enter the ETC.
How will the bodies metabolism alter if the starvation period lasts longer than 3 days?
Glycogen stores will be empty and the liver will be involved in ketone body synthesis.
The beta oxidation of fatty acids is said to resemble is said to resemble what shape?
A spiral.
What does fatty acid oxidation start with?
A fatty acyl CoA.
What does fatty acid oxidation finish with?
A fatty acyl CoA that is 2 carbons shorter than the original fatty acyl CoA.
What is generated in each of the 4 steps of the FA spiral?
- Fatty acyl (n carbons) CoA.
- Enoyl CoA + FADH2.
- Beta hydroxyacyl CoA.
- Beta ketoacyl CoA + NADH.
- Fatty acyl (n-2) CoA + ACoA.
What is the order of the 4 enzymes that are used in the FA spiral?
Acyl CoA dehydrogenase.
Hydratase + H2O.
Hydroxyacyl CoA dehydrogenase.
HSCoA + thiolase.
What happens in step 1 of the FA spiral?
Fatty acyl CoA reacts with an enzyme to make enoyl CoA and FADH2.
What is the enzyme substrate and product of step 1 of fatty acid synthesis?
Enzyme used. Acyl CoA dehydrogenase.
Substrate. Fatty acyl CoA.
Product. Enoyl CoA and FADH2.
What prosthetic group is used by acyl CoA dehydrogenase?
FAD.
Why is the fatty acid said to be n carbons long?
Because the fatty acids can be of varying length.
What happens to FADH2 that is formed by acyl CoA dehydrogenase?
It can enter the ETC.
What is the alpha carbon of fatty acyl CoA?
Carbon 2.
What is the beta carbon of fatty acyl CoA?
Carbon 3.
Does the same acyl CoA dehydrogenase work on all fatty acids?
No.
Different ACoA dehydrogenases will work on the different chains with respect to their length.
What happens in step 2 of fatty acid oxidation, once enoyl CoA has been formed?
Enoyl CoA will react with a hydratase and H2O to produce beta hydroxyacyl CoA.
What is the enzyme substrate and product of step 2 of fatty acid synthesis?
Enzyme used. Enoyl CoA hydratase + H2O.
Substrate. Enoyl CoA.
Product. Beta hydroxyacyl CoA.
What happens in step 3 of fatty acid oxidation, once hydroxyacyl CoA has been formed?
Beta hydroxyacyl CoA is oxidised to beta ketoacyl CoA and an NADH is produced.
What happens to the NADH formed in step 3 of fatty acid oxidation?
It can enter the ETC to generate ATP.
How many carbonyl groups will ketoacyl CoA have?
2.
What is the enzyme substrate and product of step 3 of fatty acid synthesis?
Enzyme used. Hydroxyacyl CoA dehydrogenase.
Substrate. Beta hydroxyacyl CoA.
Product. Beta ketoacyl CoA.
What is the prosthetic group that is used by hydroxyacyl CoA dehydrogenase?
NAD+.
What happens in step 4 of fatty acid oxidation, once beta keto acyl CoA has been formed?
Beta ketoacyl CoA is converted to fatty acyl (n-2) CoA and free CoA.
How many carbons is beta keto acyl CoA reduced by in step 4 of fatty acid synthesis?
2.
What process converts keto acyl CoA to fatty acyl CoA
Thiolytical cleavage
What replaces the ACoA that is cleaved from beta keto acyl CoA reduced by in step 4 of fatty acid synthesis?
CoASH.
What happens to the fatty acyl CoA that is formed in step 4 of fatty acid synthesis?
It will be re-entered at step 1.
How much energy can be produced from 1 cycle of fatty acid oxidation?
1 FADH2 and 1 NADH = 5 ATP.
1 ACoA = 12 ATPs in the TCA.
What is the cellular location of fatty acid synthesis and fatty acid oxidation?
FA synthesis. Cytosol.
FA degradation. Mitochondria.
How is ACoA used in fatty acid synthesis and fatty acid oxidation?
FA synthesis. ACoA is used as the substrate.
FA degradation. ACoA is the product.
What coenzymes are used in fatty acid synthesis and fatty acid oxidation?
FA synthesis. Biotin and NADPH.
FA degradation. FAD and NAD+.
What activates fatty acid synthesis?
Cytosolic ACoA.
Allosterically activated by citrate.
De-phosphorylation.
Induction by insulin.
What activates fatty acid oxidation?
High levels of free fatty acids.
Active carnitine shuttle.
What inhibits fatty acid synthesis?
Alloscterically activated by palmitoyl CoA.
Phosphorylation by AMP kinase.
Glucagon and epinephrine.
What inhibits fatty acid oxidation?
Malonyl CoA.
High ATP.
High NADH.
How will fatty acid synthesis inhibit the carnitine shuttle?
By producing malonyl CoA in the cytosol.
What is the carnitine shuttle needed for in fatty acid oxidation?
To transport of long chain fatty acids into the mitochondria.
What are unsaturated fatty acids?
Fatty acids with double bonds.
What percentage of fatty acids in humans are unsaturated?
Around 50%.
Where are unsaturated fatty acids degraded?
In the mitochondria.
Is there any difference between the degradation of fatty acids and unsaturated fatty acids?
Yes.
The degradation of unsaturated fatty acids requires 2 more enzymes.
What are the 2 extra enzymes that are needed to degrade unsaturated fatty acids?
An isomerase and a reductase.
What kind of fatty acids will not be totally degraded by fatty acid oxidation?
Fatty acid chains with odd numbers.
What happens to fatty acids with odd numbers?
They are degraded to a propionyl CoA which will enter the TCA cycle as succinyl CoA.
Can fatty acids with very long chains be degraded in the mitochondria?
No.
They have to be broken down in the peroxisomes.
What happens to the very long chain fatty acids in the peroxisomes?
They will be broken down to long chain fatty acids and transported to the mitochondria.
What does the breakdown of very long chain fatty acids to long chain fatty acids generate?
Hydrogen peroxide which is used by the catalase enzyme to detoxify molecules.
Where are branched chain fatty acids degraded?
In the peroxisomes.
What is the alpha oxidation of fatty acids?
It is the oxidation of branched chain fatty acids as the oxidation starts at the alpha carbon.
What kind of fatty acids are branched?
The fatty acids that we get from dairy products.
What do the fatty acids from dairy products contain?
Phytanic acid which is a 20C branched chain fatty acid.
What fatty acids are degraded in the mitochondria?
Unsaturated, long, medium and short chain fatty acids.
What fatty acids are degraded in the peroxisomes?
Very long and branched chain fatty acids.
What is the equation for the degradation of palmitoyl CoA?
Palmitoyl CoA + 23 O2 + 129 Pi + 129 ADP = 131 ATP + 16 CO2 + 39 H2O + free CoA.
How many ATPs are needed to break down palmitate?
2.
What is the net gain of ATP from the oxidation of palmitate?
129 ATP.
What is the gross gain of ATP from the oxidation of palmitate?
131 ATP.
The oxidation of palmitoyl CoA generates how much ATP?
131 ATP.
The oxidation of palmitate generates how much ATP?
129 ATP.
How many electrons are required to reduce 1 O2 to 2 H2O?
4.
What is the only organ that can form ketone bodies?
The liver.
What tissues can use ketone bodies for fuel?
Almost all tissues except the liver.
When are ketone bodies formed?
In the fasting state.
What are the 2 ketone bodies that are formed in the liver?
Acetoacetate and 3-hydroxybuterate.
What happens once ketone bodies are formed in the liver?
They are released into the blood and will travel to various tissues.
Will malonyl CoA inhibit the carnitine shuttle during fasting?
No.
In what state will there be an accumulation of fatty acids in the cytoplasm of liver cells?
in the fasting state.
Why does the liver make ketone bodies?
To get rid of excess ACoA.
Where does ketone body synthesis take place?
In the mitochondria of the liver in the fasting state.
What happens in step 1 of ketone body synthesis?
Acetoacetyl CoA must be formed.
What are the 2 ways that Acetoacetyl CoA can be formed in ketone body synthesis?
Acetoacetyl CoA that has already been formed is not degraded.
2 ACoA molecules are joined together by thiloase.
What happens in step 2 of ketone body synthesis once acetoacetyl CoA has been formed?
The CoA is cleaved from acetoacetyl CoA to form acetoacetate.
Can acetoacetyl CoA cross the inner mitochondrial membrane?
No.
What does acetoacetyl CoA need to be cleaved to so that it can cross the inner mitochondrial membrane?
Acetoacetate.
How is acetoacetate formed from acetoacetyl CoA?
HMGCoA synthase to add another CoA to make HMG CoA.
Why will ketone synthesis only take place in the liver?
Because HMGCoA synthase is only found in the liver.
What happens in step 3 of ketone body synthesis, once acetoacetyl CoA has been formed?
HMG CoA lyase cleaves HMG CoA to form acetyl CoA and free acetoacetate which is the first ketone body.
What happens once acetoacetate is formed in step 3 of ketone body synthesis?
It can enter the blood where it will be spontaneously degraded to acetone which is exhaled.
What happens in step 3 of ketone body synthesis, if acetoacetate does not enter the blood?
The liver will use NADH to make the much more stable 3-hydroxybuterate.
Is ATP needed to activate a ketone body?
No.
What happens when 3-hydroxybuterate enters a muscle cell?
3-hydroxybuterate is oxidised to make an NADH and acetoacetate.
Thiophorase takes an ACoA and uses it to make acetoacetyl CoA.
This gives 2 ACoA molecules that can be used for the TCA cycle.
Where does thiophorase get ACoA from when 3-hydroxybuterate has been oxidised in the muscles?
From succinyl CoA in the TCA cycle.
Why can the liver not use ketone bodies for energy?
It lacks the enzyme thiophorase.
What are blood glucose levels after 3 days of starvation?
3.8 mM and they will not change.
What happens to fatty acid levels in the blood during starvation?
They will increase.
What happens to acetoacetate levels in the blood during starvation?
They will increase, but the unstable acteoacetate will be reduced to acetone.
What happens to hydroxybuterate levels in the blood during starvation?
They will increase to around 6mM.
If 2 more carbons are added to palmitate, how many extra ATPs can be generated?
17.
