Lipids 2 Flashcards
Where does beta oxidation occur?
Mitochondrial matrix
What is produced from B-oxidation?
- Degrades FA 2 C at a time
- Produces acetyl CoA and also NADH and FADH2 which are sources of energy
What are the 3 stage of B-oxidation and where do they occur?
- Activation of FA: cytosol
- Transport into the mitochondria
- Degradation to 2 C fragments: mitochondrial matrix
What is FA activated to form?
Fatty acyl CoA I the cytoplasm
What mechanism is used in the transport of fatty acyl CoA to the mitochondrial matrix?
The Carnitine shuttle
Why is the carnitine shuttle used?
CoA is very big and can diffuse through the outer membrane but not the inner membrane
What does carnitine palmitoyl transferase I do?
Transfers FA from FA acyl CoA to carnitine
What enzyme aids the movement of FA carnitine across the membrane?
Translocase
What does carnitine palmitoyl transferase II do?
Transfers FA from FA carnitine to acyl CoA
What enzyme moves carnitine back to its original position?
Translocase
What inhibits carnitine palmitoyl transferase?
Malonyl CoA
What does malonyl Co do?
Prevents synthesis and degradation occurring simultaneously
Where do we get carnitine from/
Mainly our diet or can be made from lysine or methionine in the liver/kidney
What is occurs during carnitine palmitoyl transferase deficiency?
- No B-oxidation occurs which results in hypoglycaemia
- Coma on overnight fast
- Improved with IV glucose
- Give medium chain FA which do not require CPT1 for mitochondrial transport
What is acarnitine palmitoyl transferase deficiency?
A carnitine associated defect in liver DA B-oxidation which impairs the liver’s capacity to use FA as fuels, putting extra burden on its capacity to generate glucose through gluconeongensis
What are the 4 main stages in degradation?
-Dehydrogenation
-hydration
Dehydrogenation
Thiolysis
What does the dehydrogenation (stage 1) produce?
FADH2 from FAD
What does the dehydrogenation (step 3) produce?
NADH from NAD
What does thiolysis (step 4) produce?
Acetyl CoA which feeds into TCA cycle
What does each cycle of B-oxidation produce?
One acetyl CoA and a species 2 carbon atoms shorter than the original
What happens to very long chain fatty acids before B-oxidation?
Undergoes a preliminary B-oxidation in peroxisomes
Why is B-oxidation in peroxisomes less energy efficient?
The first step doe not produce FADH2
What happens to the shortened FA after B-oxidation in the peroxisome?
It is linked to carnitine and diffuses out of the peroxisome into the mitochondria for further oxidation
What do defects in the B-oxidation pathway in peroxisomes result in?
VLC-FA accumulation in blood and tissue
Why can animals not convert FA to glucose?
- No FA is gluconeogenic
- They are unable to convert CoA into glucose due to thermodynamically irreversible pyruvate to acetyl CoA step
What happens to excess Acetyl CoA?
Form ketone bodies
What affect does acetyl CoA have on enzymes?
- Inhibits pyruvate dehydrogenase
- Activates pyruvate carboxylase
What does the amount of ketogenesis depend on?
The availability of acetyl CoA
When is acetyl CoA converted to ketone bodies?
During fasting or starvation, when glucose is decreased
What uses ketone bodies as an energy source?
Cardiac and skeletal muscles
When can ketone bodies fuel brain cells?
During starvation
Where are ketone bodies found?
Formed in the liver in the mitochondrial matrix and is transported with the blood to other cells where it is used as fuels
What can the liver not do in regards to ketone bodies?
Use them as a fuel source
What can lead to very high ketone body concentrations in the blood?
-Uncontrolled diabetes or starvation
What happens when the rate of ketone body production exceeds utilisation?
Ketonemia, ketonuria and acidemia
When does diabetic ketosis result?
When insulin is absent
Why can Acetyl CoA not be processed after B-oxidation?
Due to a lack of glucose derived oxaloacetate
