Daya S, Nonaka K O, Buzzell G R, Reiter R J
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284.
J Neurosci Res. 1989 Jul;23(3):304-9. doi: 10.1002/jnr.490230309.
The daytime administration of the heme precursor 5-aminolevulinate (5-ALA) has been shown to reduce brain tryptophan and serotonin levels owing to saturation of liver tryptophan pyrrolase. Saturation of this enzyme with heme results in enhanced activity, leading to increased catabolism of tryptophan and thus making less tryptophan available to the brain. Tryptophan is also the precursor of melatonin, a primary secretory product of the pineal gland. Reduced melatonin levels, which could be a consequence of altered tryptophan metabolism, have been associated with depressive disorders in humans. In view of this, in the present study we examined the effects of 5-ALA administration on forebrain tryptophan and serotonin levels as well as pineal serotonin, melatonin, and the pineal melatonin-forming enzymes N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). 5-ALA induced a reduction in forebrain tryptophan and serotonin levels during the light phase and caused the opposite effect in the dark phase. Allopurinol, an inhibitor of hepatic tryptophan pyrrolase activity, prevented the reduction in the indole levels induced by 5-ALA. Although 5-ALA induced these changes in the forebrain, it did not alter either daytime or nighttime pineal NAT, HIMOT, serotonin, or melatonin levels. It appears that high serotonin levels and melatonin production in the pineal are conserved even in the face of low circulating tryptophan levels, changes which alter brain tryptophan and serotonin concentrations.
已表明，由于肝色氨酸吡咯酶饱和，白天给予血红素前体5-氨基酮戊酸（5-ALA）可降低脑内色氨酸和血清素水平。该酶被血红素饱和会导致活性增强，从而使色氨酸分解代谢增加，进而使进入脑内的色氨酸减少。色氨酸也是褪黑素的前体，褪黑素是松果体的主要分泌产物。色氨酸代谢改变可能导致褪黑素水平降低，这与人类的抑郁症有关。鉴于此，在本研究中，我们检测了给予5-ALA对前脑色氨酸和血清素水平以及松果体血清素、褪黑素和松果体褪黑素合成酶N-乙酰转移酶（NAT）和羟基吲哚-O-甲基转移酶（HIOMT）的影响。5-ALA在光照期可导致前脑色氨酸和血清素水平降低，而在黑暗期则产生相反的效果。别嘌呤醇是肝色氨酸吡咯酶活性的抑制剂，可防止5-ALA诱导的吲哚水平降低。尽管5-ALA在前脑诱导了这些变化，但它并未改变白天或夜间松果体的NAT、HIMOT水平、血清素或褪黑素水平。即使循环色氨酸水平较低，改变了脑内色氨酸和血清素浓度，松果体内较高血清素水平和褪黑素生成似乎仍得以维持。
