Fatty Acid Oxidation & Synthesis Flashcards
True/False: Fatty acid catabolism can be both and aerobic and anaerobic process?
false: requires the presence of oxygen
breakdown of free fatty acids occurs in ____ carbon increments?
two carbon increments
Where does fatty acid oxidation cleavage occur?
between the alpha and beta carbon
Where does fatty acid oxidation primarily occur? what is the exception?
the mitochondrial matrix. very long chain fatty acids (>20 carbons) are oxidized in peroxisomes
What are the main target tissues of FA oxidation?
muscles, heart, liver, kidney
Explain the process of FFA getting to and entering target cells
FFA are bound in serum to ALB, they enter target cells via transporters and are bound in the cell by fatty acid binding proteins
What is the first step of fatty acid oxidation?
They have to be converted to an active intermediate before catabolism.
How many ATP does the first step of oxidation require?
two
What enzyme is needed for the first step of FA oxidation?
Acyl CoA synthetase
Where does FA activation/step 1 occur?
cytosol
How does activated FA get transported from the cytosol into the mitochondria?
The acyl group of acyl CoA is transferred to carnitine by CPT-1, this allows it cross the inner mitochondrial membrane. Acyl CoA is then reformed by CPT-II
What two amino acids is carnitine synthesized from?
lysine and methionine
What two vitamins and mineral is required for carnitine synthesis?
vitamin C, pyridoxyl phosphate, and iron
What is the rate limiting step of FA oxidation?
CPT-I
Generally describe beta oxidation
-after acyl-CoA is transported into the mitochondrial matrix, two carbon subunits are removed as acetyl CoA
-each cycle of oxidation produces one molecule of acetyl CoA, one NADH, and one FADH2
What is a potential fate for post oxidation acetyl CoA
it can enter the TCA cycle
What are two variations of FA oxidation?
-odd chained: end result is propionyl CoA which can be converted to succinyl CoA and enter the TCA cycle
-unsaturated fatty acids: oxidized as saturated until the first double bond, converted to trans double bond,then can continue as normal
how does short and medium chain fatty acid oxidation differ from long chain?
short and medium chained fatty acids can cross the inner mitochondrial membrane without carnitine, so once inside they are activated and oxidized as normal
What does oxidation in peroxisomes yield? how is it dealt with
peroxide, it is neutralized by catalases in the peroxisome
Explain the 3 main differences between peroxisomal and mitochondrial FA oxidation
-does not require carnitine
-utilizes different enzymes
-oxidases produce FADH2 which is converted to peroxide which is neutralized by catalases
What would inhibit the rate limiting enzyme of beta oxidation?
malonyl CoA (substrate for fatty acid synthesis)
During what state in FA oxidation highest?
highest during fasting
describe how insulin and glucagon regulate fatty acid oxidation
-glucagon stimulates FA oxidation and decreases fatty acid synthesis
-lower insulin levels removes insulin inhibition of hormone sensitive lipase thereby increasing fatty acid mobilization
What is the building block of fatty acid synthesis?
acetyl CoA
Where does the initial reaction of FA synthesis take place?
cytosol
Where does FA elongation and desaturation occur?
microsomes
What are the main tissues that can perform FA synthesis?
liver, kidney, brain, lung, mammary gland, adipose
What is the initial rxn & rate limiting step of FA synthesis?
Acetyl CoA - malonyl CoA via acetyl CoA carboxylase
each reduction step of FA synthesis elongation requires what cofactor?
NADPH
What are the 3 NADPH generators that can supply FA synthesis?
-HMS
-Isocitrate dehydrogenase
-Malate dehydrogenase
what is the key regulatory enzyme in lipgenesis?
acetyl-CoA carboxylase
What allosterically activates Acetyl CoA carboxylase?
citrate
What allosterically inhibits acetyl CoA carboxylase?
long chain fatty acyl CoA (activated form of LCFA, the first step of beta oxidation)
Explain how insulin and glucagon regulate lipogenesis
-Insulin activates protein phosphatase which activates acetyl CoA carboxylase by dephosphorylating it.
-glucagon and epinephrine activate AMP dependent kinases that activate AMPK that phosphorylates and inactivates acetyl CoA carboxylase
What is the primary source of NADPH needed for lipogenesis?
HMS
What is a substantial source of NADPH in ruminants?
isocitrate dehydrogenase
What are the non ruminant sources of acetyl CoA
-ketogenic AA
-acetyl CoA formation from pyruvate
What is the role of citrate in lipogenesis?
citrate can leave the mitochondria and be converted to OAA and acetyl CoA by citrate lyase in the cytosol which provides acetyl CoA as a substrate
What are the ruminant sources of acetyl CoA
ruminants produce volatile fatty acids (propionate, acetate, and butyrate), acetate converts to acetyl CoA in the cytosol and can be used for lipogenesis
Where does fatty acid elongation occur?
microsomes
What is the acetyl donor in FA elongation?
malonyl CoA
What is the enzyme needed for FA elongation?
fatty acid elongase
