Ramchand C N, Peet M, Clark A E, Gliddon A E, Hemmings G P
Department of Psychiatry, Northern General Hospital, University of Sheffield, UK.
Prostaglandins Leukot Essent Fatty Acids. 1996 Aug;55(1-2):59-64. doi: 10.1016/s0952-3278(96)90146-5.
Two independent studies reported recently have shown a significant decrease in Vmax of tyrosine transport in fibroblasts grown from schizophrenics' skin compared with controls. It has also been shown that tyrosine transport into the brain is decreased in schizophrenics compared with controls. In view of the importance of these findings in elucidating the biochemical mechanism(s) associated with schizophrenia, we have studied the kinetics of tyrosine transport and the levels of monoamine oxidase (MAO) activity in fibroblasts grown from the skins of schizophrenics and unrelated control subjects. Using the Lineweaver-Burk plot, the Eadie Hostee plot and the Hanes plot we have calculated the Km and Vmax for tyrosine transport. We have found a significant decrease in the Km and Vmax values for tyrosine transport in schizophrenics compared with control fibroblast samples. No changes were observed in the levels of MAO. Using Lineweaver-Burk plot (1/S Versus 1/V) it has been shown that the tyrosine transport inhibition is uncompetitive. This finding proposes that the inhibition is in the substrate transport protein complex, which may be taking place during the transit of the substrate through the cell membrane. From the observed findings and from the literature evidence we suggest that the altered metabolism of phospholipids in schizophrenics, such as deficiency of arachidonic acid and docosahexaenoic acid, may be contributing to this observed phenomena.
最近两项独立研究表明，与对照组相比，精神分裂症患者皮肤来源的成纤维细胞中酪氨酸转运的最大速度（Vmax）显著降低。研究还表明，与对照组相比，精神分裂症患者大脑中的酪氨酸转运减少。鉴于这些发现对于阐明与精神分裂症相关的生化机制具有重要意义，我们研究了精神分裂症患者和无关对照受试者皮肤来源的成纤维细胞中酪氨酸转运的动力学以及单胺氧化酶（MAO）活性水平。我们使用Lineweaver - Burk图、Eadie Hostee图和Hanes图计算了酪氨酸转运的米氏常数（Km）和最大速度（Vmax）。我们发现，与对照成纤维细胞样本相比，精神分裂症患者酪氨酸转运的Km和Vmax值显著降低。MAO水平未观察到变化。使用Lineweaver - Burk图（1/S对1/V）表明酪氨酸转运抑制是非竞争性的。这一发现表明抑制作用发生在底物转运蛋白复合物中，可能发生在底物穿过细胞膜的过程中。根据观察结果和文献证据，我们认为精神分裂症患者磷脂代谢的改变，如花生四烯酸和二十二碳六烯酸的缺乏，可能是导致这一现象的原因。
