The ACC is a biotin-dependent enzyme that catalyzes the carboxylation of acetyl-CoA to produce
malonyl-CoA substrate for the biosynthesis of fatty acids [39].
The first step of fatty acid biosynthesis is the conversion of acetyl-CoA to
malonyl-CoA, catalyzed by acetyl coenzyme A carboxylase (ACC).
[sup.14]C-labeled acyl-coenzyme A (acetyl-CoA,
malonyl-CoA, and succinyl-CoA) was purchased from PerkinElmer (Waltham, MA, USA).
Paralleling its role in promoting energy expenditure through FA disposal, PPAR[alpha] also inhibits the lipogenic pathway by induction of the
malonyl-CoA decarboxylase which degrades
malonyl-CoA, a precursor of FA biosynthesis and inhibitor of the mitochondrial transporter CPT-1 [31] (Figure 1).
CHS catlyze the reaction of
malonyl-coA and coumaroyl-coA to chalcone, and is the first enzyme that leads to the synthesis of flavonoids.
This induces an increased capacity for FAO that could be due to a decreased concentration of
malonyl-CoA, attenuating the inhibition of carnitine palmitoyltransferase I (CPT1) that catalyzes the entry of FAs in mitochondria, a rate-limiting enzyme of FAO (Assifi et al.
This activated
Malonyl-CoA decarboxylase pathway reduces the level of
Malonyl-CoA (MA), inhibits the synthesis of fat, eliminates the inhibition of carnitine palmitoyltransferase 1 (CTP1) [38], promotes long-chain fatty acids in the mitochondrial inner membrane, and increases fat oxidation and decomposition [8, 39, 40].
A much more likely explanation relates to the known elevation of tissue
malonyl-CoA in the obese Zucker rats [40] which may be responsible by suppressing CPT I activity and diverting FA into storage as reviewed by [41].
The formation of stilbene phytoalexins involves the phenylalanine/polymalonate route (Figure 3), and the key step in this biosynthesis pathway is catalyzed by stilbene synthase (STS), which exerts iterative condensation reactions with
malonyl-CoA [12, 15, 16].
CPT1 activity is tightly controlled by its inhibitor,
malonyl-CoA (step 4), which is regulated by AMP-activated kinase (AMPK).