Carnitine acyltransferase acyl group transferred to carnitine, after transport across the outer
mitochondrial membrane
Acylcarnitine transported into mito. Matrix in exchange for free carnitine; carnitine then
replaced again with CoA by second acyl transferase
An unusual aspect: energy of thioester bond in acyl-CoA sufficiently well preserved in ester bond
of acyl-carnitine to allow exchange reaction to be reversed inside mito.
o Carboxyl esters dont have this
A- carbon right beside a functional group; B-carbon is the second carbon from the thioester,
where axn is in B-oxidation
The reactions are:
o Acyl-CoA dehydrogenase dehydrogenates the fatty acyl-CoA molecule between the
alpha and the beta carbon atoms
o Enoyl-CoA hydratase hydrates the trans double bond just created; alpha carbon now
once more fully reduced
o Hydroxyacyl-CoA dehydrogenase beta hydroxyl group is converted to a keto group;
NAD+ accepts the hydrogen and the product is beta-ketoacyl-Coa
o Thiolase introduces a new molecule of CoA to cleave the beta-ketoacyl-CoA, which
releases acetyl-CoA and a new, shortened acyl-CoA that enters the next cycle of beta-
oxidation
Process repeated until fatty acid completely broken down
Acyl chains with even #s of carbons yield acetyl-CoA only
Those with odd numbers of carbons yield one molecule of propionyl-CoA (special pathway to
deal with this CoA type) in the final thiolase step
* draw a mechanism*
Not very many features to rxns seen so far, but there a few familiar features:
o Cysteine thiolate performs nucleophilic attack in active site on carbonyl group in
substrate yields covalent intermediate also occurs with G-3-P dehydrogenase
o Acid-base catalysis breaks a C-C bond next to carbonyl bond; thiolate rxn reversible so
making of a C-C bond adjacent to carbonyl group via acid base catalysis occurs in reverse
rxn seen in citrate synthase rxn
o Creation of one thioester at expense of another occurs in 2nd step of PDH reaction
Draw reaction
Fatty acids with odd #s of carbons yields one propionyl-CoA as final degradation product,
which has an elaborate degradative pathway:
o First, propionyl-CoA carboxylase converts propionyl-CoA
o Methylmalonyl-CoA racemase converts S-methylmalonyl-CoA to its enantiomer R-
methylmalonyl-CoA
o Finally, methylmalonyl-CoA mutase transplants one carboxyl group within molecule
to yield succinyl-CoA, it requires Vitamin B12 in form of adenosylcobalamin as a
coenzyme
When vitamin is lacking methylmalonyl-CoA backs up and is hydrolyzed to free
methylmalonate which may inhibit gluconeogenesis
Succinyl-CoA - a TCA cycle intermediate so it can enter gluconeogenesis so that propionyl-CoA is
an exception to the rule that carbon from fatty acids cannot be used for gluconeogenesis but
not very important in odd numbered fatty acids as they amount to a small fraction of all fatty
acids
10.5.5 Fatty Acids Synthesis (2)
Cycle then repeats from here on; KS decarboxylates malonate and forms bext beta- keto
acid, KR reduces it and so on
Cycles executes 7 times overall resulting in formation of palmitate
Thioesterase activity of fatty acid synthase then releases palmitoyl reside as free palmitate
*DRAW THE PATHWAY*