TLR3 Receptor

TLRs are believed to function as dimers. Though most TLRs appear to function as homodimers, TLR2 forms heterodimers with TLR1 or TLR6, each dimer having a different ligand specificity. TLRs may also depend on other co-receptors for full ligand sensitivity, such as in the case of TLR4's recognition of LPS, which requires MD-2. CD14 and LPS Binding Protein (LBP) are known to facilitate the presentation of LPS to MD-2.


The adapter proteins and kinases that mediate TLR signaling have also been targeted. In addition, random germline mutagenesis with ENU has been used to decipher the TLR signaling pathways. When activated, TLRs recruit adapter molecules within the cytoplasm of cells in order to propagate a signal. Four adapter molecules are known to be involved in signaling. These proteins are known as MyD88, Tirap (also called Mal), Trif, and Tram.[15][16][17] The adapters activate other molecules within the cell, including certain protein kinases (IRAK1, IRAK4, TBK1, and IKKi) that amplify the signal, and ultimately lead to the induction or suppression of genes that orchestrate the inflammatory response. In all, thousands of genes are activated by TLR signaling, and collectively, the TLRs constitute one of the most pleiotropic yet tightly regulated gateways for gene modulation.

Signaling pathway of Toll-like receptors. Dashed grey lines represent unknown associations.

Biosynthesis of Fatty acid

Fatty acid are monocarboxylic acid (R-COOH) with hydrocarbon side chain of 4 to 36 carbon.

Some important feature of fatty acid biosynthesis

1. Fatty acid are degraded and synthesized by different pathway
2. Synthesis occur in cytoplasm in contrast with degardation, which occur in mitochrondria
3. Intermediates in fatty acid synthesis are attached to an acyl carrier proteins (ACP)
4. The enzyme catalyzes the reaction in fatty acid biosynthesis in higher organisms are joined in a single peptide chain called fatty acid synthase (FAS)
5. Fatty acid is built up by successive addition of 2 carbon units derived from acetyl CoA in each cycle.
6. After addition of 2-C unit, the intermediates are reduced by NADPH.

Citrate Shuttle (Click for large picture)

Citrate Shuttle

• FAs are synthesized in the cytoplasm from acetylCoA

• AcetylCoA generated from pyruvate by the action of PDH

and by β-oxidation of fatty acids is in the mitochondria.

• For fatty acid biosynthesis, acetylCoA has to be transported

from the mitochondria to the cytoplasm. This is done via a

shuttle system called the Citrate Shuttle.

• AcetylCoA reacts with oxaloacetate to give citrate. A

tricarboxylate translocase transports citrate from

mitochondria to cytosol.

• In the cytosol, citrate is cleaved back to oxaloacetate and

acetylCoA. This reaction is catalyzed by ATP-citrate lyase

and requires the hydrolysis of one molecule of ATP.

Citrate shuttle + fatty acid synthesis (Click for large picture)