Synthesis of serotonin and the blood brain barrier
Serotonin (5-HT) is synthesized in the brain from the amino acid
tryptophan. Therefore one approach to investigate the effects of 5-HT in
different settings is acute tryptophan depletion (ATD). By ingesting a drink
containing large neutral amino acids (LNAA) but no tryptophan, LNAAs compete
with endogenous TRP for transport across the blood-brain barrier (BBB),
subsequently lowering brain tryptophan levels. The rate controlling step in
central nervous 5-HT synthesis is the conversion of tryptophan into
L-5-hydroxytryptophan (5-HTP) by tryptophan hydroxylase 2 (TPH2) [Wurtmann et al 1980].
As TPH2 is not saturated at physiological concentrations of tryptophan,
diminished substrate availability for TPH2 decreases brain 5-HT synthesis and
release [Wurtmann et al 1980].