Fatty Acid Mobilization and Oxidation Flashcards
what is fatty acid utilization?
process of releasing FA from storage
what is lipolysis?
hydrolysis of FA from TAG in adipose
what is beta oxidation?
mitochondrial oxidation of FA to acetylCoA
which provides more energy glycogen or fatty acids?
fatty acids
when is serum FA low?
fed states
when is serum FA high?
stressed states (starvation, emotional)
where do TAGs come from?
dietary TAG (chylomicrons) liver TAG (VLDL) glucose (de novo TAG synthesis)
what enzyme is used to remove TAGs from lipid droplets inside cells?
adipose triglyceride lipase
how are TAGs stored inside cells?
lipid droplets
what are lipid droplets surrounded by?
phospholipid layer
what is perilipin?
binds to CGI58 and prevents it from activating adipose triglyceride lipase
what is CG158?
activates adipose triglyceride lipase
inhibited by perilipin
what does adipose triglyceride lipase do?
first step of lipolysis- removal of a fatty acid from TAG, forms DAG
what does hormone sensitive lipase do?
removes second fatty acid from the DAG
what does monoacylglycerol lipase do?
removes last FA from MAG
what is the main stimulator of the starved state?
stress
what signals lipolysis?
epinepherine and sympathetic stimulation
very few glucagon receptors on adipose cells
what signal pathway does the starved state use?
cAMP/PKA
what does PKA do during the starved state?
phophorylates perilipin- it releases CGI58
phophorylates hormone sensitive lipase
what is the rate determining step of lipolysis?
phophorylation of hormone sensitive lipase
what is the main inhibitor of lipolysis?
insulin- don’t need to mobilize TAGs if in fed state
what does insulin do?
dephosphorylates hormone sensitive lipase (via phosphatase)
decreases cAMP
how does FA travel in the blood?
bound to albumin
how many FAs can albumin hold?
8
what are the 2 things that can happen to fatty acids once inside a cell?
- bound by fatty acid binding protein to store
- converted to FA acyl CoA by acyl-CoA synthetase
what type of chains enter mitochondria?
short/medium chains (less than 18)
what type of chains go to peroxisomes?
long chain (greater than 18)
how do fatty acyl-CoAs get into mitochondria
- cross outer membrane freely
- converted to fatty acylcarnitine by carnitine palmitoyltransferase (adds free carnitine and takes off the CoA)
- carnitine acylcarnitine trnaslocase brings it into the matrix and kicks a carnitine into the inner membrane space
- CPTII converts the fatty acyl carnitine back to fatty acyl CoA
how many pools of CoA are in the mitochondria?
2- inner membrane space and matrix
how is CPT regulated?
inhibited by malonyl CoA from acetyl CoA carboxylase during fed state- sends FAs to be stored
what are the steps of mitochondrial beta oxidation of fatty acids?
- dehydrogenation via acetylCoA dehydrogenase (FAD part of electron transport chain)
- hydration
- dehydrogenation- NAD
- cleavage
what are symptoms of acetylCoA dehydrogenase deficiency?
muscle weakness
lack of ketones (no acetyl CoA)
acyl carinitines in urine
how do long chain fatty acids enter the peroxisome?
ABC proteins
what are the steps of peroxisome beta oxidation
- dehydrogenation linked to catalase
- hydration
- dehydrogenation
- cleavage
why is catalase necessary in the first step of peroxisome beta oxidation?
no electron transport chain to take the reducing equivalents from FAD
FAD gives them to O2, forming hydrogen peroxide
catalase oxidizes H2O2 to O2 and H2O
how far does the peroxisome oxidize FA chains?
down to 8-10 FAs so they can get into the mitochondria
what is peroxisome proliferation used for?
deal with high serum TAG presence
increase number of peroxisomes to deal with excess long chain fatty acids
results in decreased VLDL in blood
what are 3 fates of FA in liver?
beta oxidation
peroxisome oxidation
resynthesis of TAGs
what is left after complete oxidation of odd chain fatty acids?
propinoyl CoA (used as a substrate for gluconeogenesis)
what are the enzymes of odd chain fatty acid oxidation?
propionyl CoA carboxylase
racemase
methylmalonyl-CoA mutase
how are odd chain fatty acids oxidized?
beta oxidation down to propinoyl
then propionyl CoA carboxylase
racemase
methylmalonyl-CoA mutase
what does propionyl CoA carboxylase do?
turns propionyl CoA to methylmalonyl CoA
what does racemes do?
switches form of methylmalonyl CoA
what does methylmalonl-CoA mutase do?
turns methylmalonyl CoA to succinyl CoA (succinyl CoA enters TCA cycle)
requires biotin to add a carbon via HCO3-
how can odd chain fatty acid oxidation help in acylCoA dehydrogenase deficiencies?
give patients odd chain fatty acids so they can be processed this way to avoid the missing dehydrogenase
-enhances gluconeogenesis with anapleurotic reactions
