Regulatory Role of Free Fatty Acids (FFAs)—Palmitoylation and Myristoylation


Multicellular organisms use chemical messengers to transmit signals among organelles and to other cells. Relatively small hydrophobic molecules such as lipids are excellent candidates for this signaling purpose. In most proteins, palmitic acid and other saturated and some unsaturated fatty acids are esterified to the free thiol of cysteines and to the N-amide terminal. This palmitoylation process enhances the surface hydrophobicity and membrane affinity of protein substrates and plays important roles in modulating proteins trafficking, stability, and sorting etc. Protein palmitoylation has been involved in numerous cellular processes, including signaling, apoptosis, and neuronal transmission. The palmitoylation process is involved in multiple diseases such as Huntington’s disease, various cardiovascular and T-cell mediated immune disorders, as well as cancer. Protein palmitoylation through the thioester (S-acylation) is unique in that it is the only reversible lipid modification. Our study on lipopolysaccharide (LPS) and deoxynivalenol (DON) treatment to rats provides some insights to the complex role of protein palmitoylation in chemical and microbial toxicity. In contrast, myrisoylated proteins contain the 14-carbon fatty acid myristate attached via amide linkage to the N-terminal glycine residue of protein, and occur cotranslationally. The bacterial outer membrane enzyme lipid A palmitoyltransferase (PagP) confers resistance to host immune defenses by transferring a palmitate chain from a phospholipid to the lipid A component of LPS. PagP is sensitive to cationic antimicrobial peptides (CAMP) which are included among the products of the Toll-like receptor 4 (TLR4) signal transduction pathway. This modification of lipid A with a palmitate appears to both and protects the pathogenic bacteria from host immune defenses and attenuates the activation of those same defenses through the TLR4 signal transduction pathway.

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C. Kim and I. Ross, "Regulatory Role of Free Fatty Acids (FFAs)—Palmitoylation and Myristoylation," Food and Nutrition Sciences, Vol. 4 No. 9A, 2013, pp. 202-211. doi: 10.4236/fns.2013.49A1028.

Conflicts of Interest

The authors declare no conflicts of interest.


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