TITLE:
Regulatory Role of Free Fatty Acids (FFAs)—Palmitoylation and Myristoylation
AUTHORS:
Chung S. Kim, Ivan A. Ross
KEYWORDS:
Free Fatty Acids; Palmitoylation; Myristoylation; Microbial and Chemical Toxicity; Innate Immune Response
JOURNAL NAME:
Food and Nutrition Sciences,
Vol.4 No.9A,
September
23,
2013
ABSTRACT: 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.