Lipid Mobilization and Catabolism; Ketone body synthesis and utlization Flashcards
Fatty acids in TAG are released as free fatty acids during fasting by which enzyme?
Hormone Sensitive Lipase
What inhibits hormone sensitive lipase during the well fed state?
Insulin
Deficiency of what hormone during fasting stimulates hormone sensitive lipase?
Insulin
Besides absence of insulin, what else stimulates hormone sensitive lipase?
Epinephrine
Glucagon
How does epinephrine stimulate hormone sensitive lipase?
- via cAMP
- activates protein kinase
Is hormone sensitive lipase active in the phosphorylated or dephosphorylated form?
Phosphorylated
Why can’t glycerol formed in the adipose tissue from lipolysis be reused?
Adipose lacks glycerokinase
Once glycerol is formed via Lipolysis in adipose tissue, where does it go? What does it do there?
1)Liver
2)Enters:
-Glycolysis
or
-Gluconeogenesis
or
-Triacylglycerol synthesis
How is free fatty acids transported in circulation?
Albumin
Once free fatty acids are made via lypolysis, where is it transported to?
Liver and muscle (skeletal; cardiac)
Are free fatty acids oxidized for energy by the brain?
No
NOT an important fuel source in brain even in starvation
In B-oxidation, what part of the fatty acid is oxidized?
B-carbon atom of fatty acid
Where in the cell does B-oxidation occur?
Mitochondria
What are the 3 staged of B-oxidation?
- Activation of fatty acid (cytosol)
- Transport of fatty acid into mitochondria
- -B-oxidation rxns
What activates fatty acids to fatty acyl coA in order to initial B-oxidation?
Fatty Acyl CoA synthetase
What is another name for fatty acyl coA synthetase?
Thiokinase
What else does thiokinase need along with a fatty acid molecule in order to make fatty acyl coA?
- CoASH
- ATP
Where is fatty acyl CoA synthetase found?
Outer mitochondrial membrane (cytosolic side)
What is the role of Carnitine Palmitoyl Transferase I (CPT-1)?
Binds Carnitine to the fatty acyl group to form Acyl-Carnitine
How does Acyl-Carnitine cross the inner mitochondrial membrane to enter the mitochondrial matrix?
Translocase
What is the role of Carnitine Palmitoyl Transferase -II (CPT-II)?
Removes carnitine from acyl group forming Fatty Acyl CoA in the matrx
How does carnitine get from the mitochondrial matrix back to the intermembrane space?
Translocase
Can fatty acid synthesis occur during the same time as B-oxidation?
No
How is CPT-I inhibited?
Malonyl CoA
How do fatty acids cross the mitochondrial membrane without the aid of carnitine or CPT?
When they are shorter than 12 C atoms
What tissues are different isoforms of CPT-I and CPT-II located?
Liver
Muscle
Where is the location of the enzymes needed for B-oxidation?
Mitochondrial matrix
What is the sequence of reactions of B-oxidation?
- Oxidation (removal of H) (req FAD)
- Addition of water
- Oxidation (removal of H) (req NAD+)
- Cleavage
One sequence of reactions in B-oxidation results in what?
-Cleavage of 2 C-atoms
removed as Acetyl CoA
What enzyme family performs the 1st oxidation step in B-oxidation?
Acyl CoA Dehydrogenase
What enzyme adds water in the second step of B-oxidation?
Enoyl CoA Hydratase
Which enzyme is needed in the 3rd step of oxidation in B-oxidation?
3-hydroxy acyl CoA dehydrogenase (req NAD+)
What performs the cleavage step during B-oxidation?
Thiolase
What energy molecule does Acyl CoA Dehydrogenase create?
FADH2 (equivalent to 2 ATP)
What energy molecule does 3-hydroxy acyl CoA dehydrogenase create?
NADH + H+
What is the most common inherited autosomal recessive enzyme deficiency for B-oxidation
Medium Chain Acyl CoA dehydrogenase (MCAD) deficiency
What can patients with MCAD deficiency not do?
Decreased ability to oxidize fatty acids with 6-10 C atoms
What occurs in patients with MCAD deficiency during fasting?
Severe hypoglycemia
Why does MCAD deficiency produce severe hypoglycemia?
During fasting, no B-oxidation for energy, therefore rely on glucose.
For patients with MCAD deficiency, what is found in the urine?
- Medium Chain Acyl Carnitines
- Dicarboxylic acids
Why are dicarboxylic acids found in the urine for patients with MCAD deficiency?
Increased flux through omega-oxidation.