Transportation of Acetyl Co A

Fatty acids are synthesized in the cytosol, whereas acetyl CoA is formed from pyruvate in mitochondria. Hence, acetyl CoA must be transferred from mitochondria to the cytosol. Mitochondria, however, are not readily permeable to acetyl CoA. Carnitine carries only long-chain fatty acids. The barrier to acetyl CoA is bypassed by citrate, which carries acetyl groups across the inner mitochondrial membrane. Citrate is formed in the mitochondrial matrix by the condensation of acetyl CoA with oxaloacetate (Figure-1 ).

Figure-1- Transportation of Acetyl Co through citrate transporter

When present at high levels, citrate is transported to the cytosol, where it is cleaved by ATP-citrate lyase. which increases in activity in the well-fed state. The acetyl-CoA is then available for malonyl-CoA formation and synthesis to palmitate (Figure).

Oxaloacetate formed in the transfer of acetyl groups to the cytosol must now be returned to the mitochondria. The inner mitochondrial membrane is impermeable to oxaloacetate. Hence, a series of bypass reactions are needed. Most importantly, these reactions generate much of the NADPH needed for fatty acid synthesis.

First, oxaloacetate is reduced to malate by NADH. This reaction is catalyzed by a malate dehydrogenase in the cytosol.

Second, malate is oxidatively decarboxylated by an NADP + -linked malate enzyme (also called malic enzyme).

The pyruvate formed in this reaction readily enters mitochondria, where it is carboxylated to oxaloacetate by pyruvate carboxylase.

The sum of these three reactions is-

Thus, one molecule of NADPH is generated for each molecule of acetyl CoA that is transferred from mitochondria to the cytosol. Hence, eight molecules of NADPH are formed when eight molecules of acetyl CoA are transferred to the cytosol for the synthesis of palmitate. The additional six molecules of NADPH required for this process come from the pentose phosphate pathway.

Alternatively, malate itself can be transported into the mitochondrion, where it is able to re-form oxaloacetate. Note that the citrate (tricarboxylate) transporter in the mitochondrial membrane requires malate to exchange with citrate (see Figure 13-10). There is little ATP-citrate lyase or malic enzyme in ruminants, probably because in these species acetate (derived from the rumen and activated to acetyl-CoA extra-mitochondrial) is the main source of acetyl-CoA.