Fatty Acid Degradation Flashcards
What form of fatty acid is stored in adipose?
Muscle? (2)
Body fluids?
Liver?
Triglycerides
Glycogen/protein
Free glucose
Glycogen
In the liver, what can be used to produce ketone bodies?
Acetyl CoA
Why does the brain have a limited capability to beta-oxidation of fatty acids?
Because FAs cannot pass the blood-brain barrier
What are the two main sources of fatty acids in the well fed state? What’s the difference?
Chylomicrons – formed in the intestinal epithelium from FA in diet, they go in the circulation where FAs are removed through the peripheral tissues
Very low density lipoprotein – from glucose synthesized to become FAs, packaged in the liver
What is the source of FAs in the fasting or exercising state? What is FA broken down from? What enzyme is used? How is it regulated?
FA is taken from adipose tissue, it is broken down from triglycerides by hormone sensitive lipase. High glucagon/insulin ratio and high epinephrine levels activate this
What happens to the FAs released from adipose tissue?
They are bound to albumin (transporter) and delivered to target tissues. Fatty acid binding protein in the plasma membrane transports them inside the cell to be degraded mainly in the mitochondria
Describe the long chain FA transport into mitochondria
Acyl CoA will be added to FA through acetyl CoA synthetase
Fatty acyl CoA will cross the outer membrane, the CoA will be removed to be replaced by carnitine to form fatty acyl carnitine using CTP-1
It will cross the inner membrane through carnitine translocate
Carnitine will be removed and replaced by CoA to form fatty acyl CoA all by CPT-2
Fatty acyl CoA will go on to beta-oxidation
How is carnitine synthesized? What is required as a donor?
Where is it synthesized? Where is it stored afterwards?
What is it used for?
It is synthesized from protein-bound lysine, synthesis requires S-adenosyl-methionine (SAM) as methyl donor
Synthesis starts in the skeletal muscle, completed in liver and kidney, stored in skeletal muscle afterwards
Used as dietary supplement to speed up FA oxidation
What happens in the deficiency of carnitine metabolism?
What does it lead to?
What is elevated?
How is it treated?
Unable to degrade long chain FA, manifests during fasting or infections
Leads to hypoketotic hypoglycemia during fasting, ketone bodies not produced in liver, gluconeogenesis will be deficient, glucose is not spared in circulation
Blood levels of liver enzymes and ammonia
High carb, low fat diet rich in medium chain length fatty acids (does not require carnitine)
What is low/elevated in the following carnitine deficiencies:
Primary carnitine deficiency
CPT-1 deficiency
Acylcarnitine translocase deficiency
CPT-2
Low plasma carnitine and acyl carnitine level, elevated carnitine in urine
Elevated free carnitine plasma level, elevated free carnitine/acyl (C16-18) carnitine ratio
Low plasma free carnitine level/elevated acyl(C16-18) carnitine levels
Low plasma free carnitine levels/elevated acyl(C16-18) levels
What comes out of one cycle of beta-oxidation?
How do you calculate what is produced?
1 molecule of FADH2, NADH, and Acetyl CoA
Half the molecule, subtract by one
Where are medium-chain fatty acids formed?
Some are produced in peroxisomes from very long chain of fatty acids, they are transported into the mitochondria where beta-oxidation proceeds
What is elevated in Medium Chain Acyl CoA DH (MCAD) deficiency? How is it treated?
C6-C10 acyl carnitine levels and C6-C10 dicarboxylic acids in urine (due to omega oxidation)
Treated with glucose and carb rich diet
How is beta-oxidation regulated?
Malonyl CoA, which forms from acetyl CoA formed though acetyl CoA carboxylase, inhibits CPT-1. Acetyl CoA carboxylase is activated by insulin and inhibited by AMP-PK. NADH as well as FADH2 inhibits beta oxidation
Where does omega oxidation take place?
What is produced?
When is it activated?
It takes place in the SER
Dicarboxylic acid is produced
It is activated when beta-oxidation is deficient
