Is there a single malonyl‐CoA pool in the heart for regulation of carnitine palmitoyltransferase‐I and fatty acid chain elongation

In non‐lipogenic tissues malonyl‐CoA serves two functions: 1) regulation of mitochondrial fatty acid oxidation via inhibition of carnitine palmitoyltransferase‐I (CPT‐I), and 2) providing two‐carbon units for fatty acid chain elongation. In the presence of acetyl‐CoA carboxylase (ACC‐2) substrates acetyl‐CoA, ATP‐Mg 2+ , and bicarbonate isolated rat heart mitochondria synthesize malonyl‐CoA that results in inhibition of CPT‐I. Furthermore, addition of palmitoyl‐CoA and NADPH/NADH to isolated intact rat heart mitochondria catalyze the incorporation of radioactive malonyl‐CoA into lipid soluble products suggesting an outer mitochondrial membrane localization of the long‐chain fatty acid elongation pathway. These data suggest that malonyl‐CoA formed by mitochondrial ACC‐2 is available for both, regulation of fatty acid oxidation and for fatty acid chain elongation. The finding with perfused heart that stable isotope labeled palmitate is chain‐elongated to stearate without prior chain shortening by β‐oxidation and isotope dilution as judged from the near identical isotope enrichment of palmitoyl‐ and stearoylcarnitine is in support of this. These data and the exclusive outer mitochondrial membrane localization of CPT‐I suggests that mitochondria catalyze long‐chain fatty acid elongation also in vivo . Our data raise the question about metabolic channeling of malonyl‐CoA between ACC‐2, CPT‐I, and fatty acid chain elongation and how these processes are regulated. Supported by: DK‐066107, POI AG15885, and VA Med. Res. Serv.