Fatty Acid Oxidation Flashcards
What is the first step of fatty acid oxidation and what is required to drive the reaction?
Activation of FA via binding with CoA-S to form acylCoA.
Requires input of ATP -> AMP +PP
How is a FA brought into the mitochondrial membrane? enzyme responsible?
Via binding of carnitine, which has a hydroxyl group that attacks the carbonyl carbon of FAs and binds itself. The enzyme is carnitine palmitoyl transferase - I.
How does acyl carnitine enter into the mitochondrial matrix?
Via transporter - acyl carnitine translocate, on the inner mitochondrial membrane
What is the rate-limiting/regulated step of B-oxidation?
Reaction of carnitine and acylCoA catalyzed by carnitine palmitoyl transferase I.
What inhibits B-oxidation of fatty acids and at which enzyme?
Malonyl CoA (precursor for fatty acid synthesis) inhibits carnitine palmitoyl transferase I.
What are the steps of fatty acid oxidation?
- FAs react with S-CoA to make activated form acyl CoA 2. Acyl CoA reacts with carnitine to make molecule that can move through the mito membrane via acyl carnitine translocase
- Acyl carnitine moves into mito matrix
- Carnitine is removed via carnitine palmitoyl transferase II, which catalyzes CoA-SH suffer attacking carnitine bond with carbonyl of FA
- Acyl CoA undergoes repeated 4 steps to produce acetyl CoA -> TCA cycle -> ATP. And acylCoA that is 2-carbons shorter each time, and FADH & NADH -> ETC -> ATP
What happens to fatty acids in exercising muscle?
they are broken down into acetyl CoA -> TCA -> ATP drives muscle cell contraction
What happens to fatty acids in liver cells?
they are either used to generate ATP to fuel gluconeogensis or converted into ketones to fuel the CNS during fasting periods
What is the role of hormone sensitive lipase in fatty acid oxidation?
HSL is activated by phosphorylation in GCPR cascade in response to the cell needing energy, and causes cells to release fat droplets
What do triglyceride lipase do?
catalyze hydrolysis of triglycerides into glycerol and 3 fatty acids
What is propionyl-CoA and how is it utilized?
it is a 3-carbon product of fatty acid oxidation of fatty acid with an odd # of carbons. It is utilized by converting it into a 4-carbon intermediate (succinyl-CoA)
What are the 4 steps (in cycle) of beta oxidation?
oxidation, hydration, oxidation, thiolysis
What are the characteristics of carnitine deficiency/cranitine transporter defect?
high plasma triglycerides
hypoglycemia
lipid vacuoles in muscle biopsy
progressive cardiomyopathy and skeletal muscle weakness
How can people affected by carnitine transporter defect still have some fatty acid breakdown?
fatty acids that are smaller than 12 carbons can cross the mitochondria membrane without the carnitine shuttle
How does deficiency of acylCoA dehydrogenase cause hypoglycemia?
It disrupts the 4-step cycle of beta oxidation of fatty acids, causing impaired ketone synthesis leading to increased demand for glucose that the liver cannot meet due to lack of energy
