Fatty acid oxidation Flashcards
hormone mediated TAG degradation in adipocyte
cAMP is produced in the adipocyte when one of several hormones (primarily epinephrine) binds to receptors on the cell membrane, and activates adenylate cyclase.
Hormone-sensitive lipase (HSL) is activated when phosphorylated by a cAMP-dependent protein kinase.
In the presence of high levels of insulin and glucose, HSL is dephosphorylated, and becomes inactive.
Glycerol
glycerol to glycerol phosphate using glycerol kinase (liver)
Fatty acid
uses fatty acyl coa synthetase and fatty acyl CoA enters mitochondrion for Beta oxidation
Carnitine
used to move fatty acids into the mitochondrion
Long chain acyl CoAs are not able to cross the inner membrane.
The transported form is acyl-carnitine, which is synthesized by carnitine acyltransferase I (CAT I) (also called carnitine palmitoyltransferase I, CPT I) using acyl CoA and carnitine as substrates.
Inside the mitochondrial matrix the acyl-carnitine is reconverted to acyl CoA.
CAT I is the rate limiting step in b-oxidation. It is allosterically inhibited by malonyl CoA.
Carnitine deficiency
- result in massive triacylglycerol deposits in the liver
- also result in muscle cramping, hypoglycemia, weakness, or death
acyl coA dehydrogenase
-saturated bond to double bond in beta oxidation
Locate in the mitochondrial matrix.
Oxidize acyl CoAs.
Four forms of the enzyme exist specific for short (4-8), medium (4-14) and long (12-18) and very long carbon chains.
Use FAD and introduce a trans double bond.
Genetic defects in all four enzymes have been described. Results in severe hypoglycemia provoked by fasting. May be a significant cause of “Sudden Infant Death Syndrome”.
Enoyl CoA hydratase
In Beta oxidation
adds water across the trans double bond from earlier step
enoyl CoA–> 3-hydroxyacyl CoA
Beta-hydroxy-CoA dehydrogenase
Oxidizes the hydroxyl generating Beta-keto-acyl-CoA and NADH from NAD
3hydroxyacyl Coa–> 3 ketoacyl Coa
Thiolase
Releases acetyl CoA and transfers the fatty acid shortened b
Energy from fatty acid oxidation
4 step repeated reaction
Each step loses 2C as acetyl coA to
generate NADH and FADH2
Use FADH2 NADH and acetyl CoA to get ATP
Odd number chain fatty acids
need an extra step:
the last round leaves a fatty acyl CoA with three carbons (propionyl CoA).
propionyl CoA carboxylase adds a carboxyl group to the fatty acidcreating D-methylmalonyl Coa, which is converted to L— and then rearranged to succinyl CoA by methylmalonyl Coa mutase in Vit B12 requiring rxn
Succinyl Coa goes to TCA
Vit B12 def
Deficiency of the mutase or in converting Vitamin B12 to the coenzyme form causes methylmalonic acidemia and aciduria because of the accumulation of propionate and methylmalonate in cells.
Peroxisomal Beta oxidation
Peroxisomes are also a major site of b-oxidation.
Very long chain and branched (phytanic acid from plants) fatty acids are preferentially oxidized in peroxisomes.
Although the intermediates are the same the enzymes are unique to peroxisomes.
Some medium chain fatty acids are exported from peroxisomes to the mitochondria for further oxidation.
Zellweger syndrome and X-linked adrenoleukodystrophy are related to defects of peroxisomal b-oxidation.
alpha oxidation of fatty acids
Phytanic acid, a branched-chain fatty acid.
It is not a substrate of acyl CoA dehydrogenase.
It is hydroxylated at the a-carbon by fatty acid
a-hydroxylase, then decarboxylated and
activated to its CoA derivative for b-oxidation.
Deficiency of a-hydroxylase causes Refsum disease.
Acyl CoA dehydrogenase deficiencies
Medium chain dehydrogenase deficiency is most common (1 in 12,000 births in U.S.)
Characterized by:
Hypoglycemia, sleepiness, vomiting, coma
increased urinary excretion of carnitine esters
low tissue carnitine levels
low levels of ketone bodies in fasting state
Can be treated with a low fat, high carbohydrate diet
May be related to SIDS
(medium chain FAs are very high in milk)
