Tryptophan

http://biopsychiatry.com/tryptophan/index.html

General Features
Abbreviation: Trp or W
Molecular Formula: C₁₁H₁₂N₂O₂
pKa: 2.38 (carboxyl), 9.39 (amino)


Tryptophan is encoded as the codon UGG.  Only the L-stereoisome is used in enzyme and structural proteins.  D-Trp is occasionally found in some naturally produced peptides.  Tryptophan is essential.  If it is not provided in growth media, tryptophan must be synthesized by the bacterium.


Synthesis

The synthesis of tryptophan is complex.  The pathway begins with chorismate.  Glutamate donates an amine group to chrosimate in the first step and pyruvate is lost.  This results in the synthesis of anthranilate.  Anthranilate condenses with phosphoribosylpyrophosphate (PRPP).  Pyrophasphate is generated as a by-product.  A ribose sugar is added.  This contributes to the 5-member ring of tryptophan.  The hydrolysis of pyrophosphate helps drive the addition of the ribose sugar in the second step of the reaction.  In the last step, serine donates a carbon amino group to tryptophan.

http://wickershamsconscience.wordpress.com/2011/11/24/trypytophan-turkey-and-post-prandial-drowsiness/

Regulation of Tryptophan Synthesis
The Trp operon regulates the production of tryptophan.   There are several methods for the regulation of tryptophan.  The first method is negative transcriptional regulation by TrpR repressor.  In this method, tryptophan is the effector (or co-repressor).

http://bio1151.nicerweb.com/Locked/media/ch18/trp_operon.html

In the absence of tryptophan, transcription of the Trp operon is on and tryptophan is synthesized. The Trp operon includes trpR, which encodes the repressor.  When the Trp operon is on, the repressor is made in the inactive form (apo repressor). For more information of the repressor, see trp Aporepressor Production is Controlled by Autogenous Regulation and Inefficient Translation by Richard L. Kelly and Charles Yanofsky.  In the presence of tryptophan, tryptophan binds to the inactive repressor.  This causes a conformational change and activate the repressor.  Two active repressors come together to form a dimer.  The dimer then binds to the operator region, preventing the RNA polymerase from binding and transcription of the Trp operon is turned off.


The second method is translational based-transcriptional attenuation.  In this method, transcription terminates in the trp operon before the RNA polymerase can transcribe the first structural gene of the trp operon.  Termination occurs within the trpL leader region. This region includes four short sequences designated 1-4.  These sequences are partially complementary and hairpin loops can form.  Three different hairpins are possible: 1-2, 2-3, and 3-4.  The 3-4 hairpin is a transcription terminator.  Once this hairpin forms, RNA polymerase will disassociate from the DNA and transcription will not occur.

The leader region contains two adjacent tryptophan (trp) codons.  In the absence of tryptophan, the ribosome will stall at one of the two trp codons. This blocks sequence 1and prevents the formation of the 1-2 hairpin.  The 2-3 hairpin (anti-termination hairpin) then forms. Formation of the 2-3 hairpin prevents the formation of the 3-4 termination hairpin.   This allows the RNA polymerase to transcribe downstream genes.  In the presence of tryptophan, the ribosome does not stall at the trp codon.  This allows the 3-4 hairpin to form.  The ribosome translates the entire leader peptide sequence and stalls at the terminator hairpin.  This prevents downstream genes from being transcribed.

This method is possible because prokaryotes begin translating mRNA while the RNA polymerase is still transcribing the DNA sequence. For more information, please read trp RNA-Binding Attenuation Protein (TRAP)-trp Leader RNA Interactions Mediate Translation as well as Transcriptional Regulation of the Bacillus subtilis trp Operon by Enrique Merino, Paul Babitzke, and Charles Yanofsky.

http://www.nature.com/scitable/content/two-different-secondary-structures-may-be-formed-19425