L24-metabolism Of Free Fatty Acids Flashcards
What does the b oxidatuon pathway achieve
Catabolism of free fatty acids by removal of 2 carbon fragments producing acetyl co a,NADH and FADH2
What are the conditions in which beta oxidation is increased
Prolonged fasting Depletion of glycogen stores Starvation Diabetes mellitus Ketogenic diets
How does activation of fatty acids occur
Conversion to acyl CoA by:
When a Fa enters cytosol its converted to CoA by thiokinase an enzyme in outer mitch membrane
Uses 2 ATP
How does process of translocation occur
▪️Carnitine shuttle(rate limiting step)
▪️Acyl group is transferred from CoA to carnitine by carnitine palmitoyltrasnferase(CPT-I)(outer)
▪️Forms acylcarnitine and CoA
▪️Acylcarintine is transported to mitch matrix in exhchange for free carnitine by acylcarnitine transolcase
▪️CPT-II (inner)catalyzes transfer of acyl group from carnitine to CoA in mitch matrix thus generating free carnitine
What is the inhibitor of the carnitine shuttle
Malonyl coA inhibits CPT-1
Prevents entry of LCFA
What are carnitine sources
Diet in meat products
Synthesized from amino acids lysine and methionine by enzymatic pathway in liver and kidnes
What can cause carnitine deficiency
Symptoms
Treatment
Congenital due to defects in transporter or aqquired as in patients with liver disease or taking anti seizure valporic acid(dec renal absorption)
Can present as hypoglycemia during fasting
Muscle weakness
Myoglibinemia after exercise
Treatment: avoidance of fasting and adpoting a high carb diet low in fat
What is the sequence of beta oxidation reactions
Oxidation: produces FADH2 Hydration Oxidation: produces NADH and coA Thioloytic cleavage:releases acetyl coA Number of cycles calculated as n/2-1(n=number of carbons)
Describe MCFA deficiency
Autosomal recessive disorder
Most common inborn error of beta oxidation
Dec ability to oxidize fatty acids with 6 to 10 carbons
Severe hypoglycemia and hypoketonemia
What are the minor pathways of fatty acid oxidation
Oxidation of fatty acids with an odd number of carbons Unsaturated fatty acid beta oxidation Peroxisomal beta oxidation Peroxisomal alpha oxidation Omega oxidation of fatty acids
Describe oxidation of fatty acids with an odd number of carbons
Proceeds by same steps of fatty that has even number until the final proionyl coA is produced instead of acetyl coA
Metabolized using biotin and b12 to give succinyl coA
Describe the process of unsaturated fatty acid beta oxidation
Additional enzymes are used to act on the double bond and break it sometimes NADPH is required and this type of oxidation produces less energy than oxidation of saturated fatty acids
Describe peroxisomal beta oxidation
VLCFA>22 in length 
Undergo a preliminary beta oxidation in paroxysms because peroxisome’s and not mitochondria are the primary site of the sythetase that activates fatty acids of this length
Shorten fatty acid refuses to mitochondria for further oxidation No NADH or FADH is produced
instead H2O2 is produced and then degraded by catalase
Final products are ocatanoyl-CoA and acetyl coA
Describe peroxisomal alpha oxidation
Very long fatty acids, branched chain fatty acids are metabolized by alpha oxidation which releases a terminal carboxyl as carbon dioxide one at a time this occurs mainly in brain and nervous tissue
Describe omega oxidation
Oxidation at the terminal carbon can be carried out by enzymes in the endoplasmic reticulum creating a Dicarboxylic acid
this process requires cytochrome P450 NADPH and molecular O2
normal beta oxidation can then occur at both ends of the fatty acid
