The biosynthesis of 5-hydroxytryptamine in brain.
1. Studies on the anatomical distribution of tryptophan 5-hydroxylase in dog brain show that the activity of this enzyme parallels the activity of 5-hydroxytryptophan decarboxylase and the concentration of 5-hydroxytryptamine in various areas of the brain. 2. Subcellular fractionation of homogenates of rabbit hind-brain has shown that at least 40% of the tryptophan 5-hydroxylase activity is associated with the crude mitochondrial fraction; equilibrium centrifugation in a discontinuous sucrose gradient suggests that this particulate tryptophan 5-hydroxylase is localized in the synaptosomes (nerve-ending particles). 3. Attempts to increase the activity of tryptophan 5-hydroxylase in iso-osmotic homogenates of brain by adding 5,6,7,8-tetrahydro-6,7-dimethylpteridine failed. 4. Procedures designed to rupture synaptosomes caused a fall in the activity of tryptophan 5-hydroxylase, which fall was reversed by adding 5,6,7,8-tetrahydro-6,7-dimethylpteridine. This suggested either that the intact synaptosome, in which the tryptophan 5-hydroxylase is localized, contained an optimum amount of the pteridine, or that the pteridine could not pass across the nerve-cell membrane. 5. Partial purification of tryptophan 5-hydroxylase from brain preparations by ammonium sulphate precipitation revealed that the enzyme was completely dependent on 5,6,7,8-tetrahydro-6,7-dimethylpteridine for activity.
D000446:Aldehyde-Lyases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000201:enzymology*; D001923:Brain Chemistry; D002247:Carbon Isotopes; D002499:Centrifugation, Density Gradient; D004285:Dogs; D008854:Microscopy, Electron; D009411:Nerve Endings / Q000201:enzymology; D011621:Pteridines / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000096:biosynthesis*
D002247:Carbon Isotopes; D011621:Pteridines; D012701:Serotonin; D000446:Aldehyde-Lyases