Kurup Ravi Kumar, Kurup Parameswara Achutha
Department of Neurology, Medical College Hospital, Trivandrum, Kerala, India.
Int J Neurosci. 2003 Sep;113(9):1221-40. doi: 10.1080/00207450390232328.
The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. It was considered pertinent to assess the pathway in inflammatory bowel disease (ulcerative colitis and regional ileitis). Since endogenous digoxin can regulate neurotransmitter transport, the pathway and the related cascade were also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. All the patients with inflammatory bowel disease were right-handed/left hemispheric dominant by the dichotic listening test. The following parameters were measured in patients with inflammatory bowel disease and in individuals with differing hemispheric dominance: (1) plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; (2) tryptophan/tyrosine catabolic patterns; (3) free-radical metabolism; (4) glycoconjugate metabolism; and (5) membrane composition and RBC membrane Na+-K+ ATPase activity. Statistical analysis was done by ANOVA. In patients with inflammatory bowel disease there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. Inflammatory bowel disease is associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to immune activation, defective glycoprotein bowel antigen presentation, and autoimmunity and a schizophreniform psychosis important in its pathogenesis. The biochemical patterns obtained in inflammatory bowel disease is similar to those obtained in left-handed/right hemispheric dominant individuals by the dichotic listening test. But all the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Inflammatory bowel disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.
类异戊二烯途径产生三种关键代谢产物——内源性地高辛、多萜醇和泛醌。评估该途径在炎症性肠病（溃疡性结肠炎和局限性回肠炎）中的情况被认为是有意义的。由于内源性地高辛可调节神经递质转运，因此还对不同半球优势的个体的该途径及相关级联反应进行了评估，以探究半球优势在其发病机制中的作用。通过双耳分听测试，所有炎症性肠病患者均为右利手/左半球优势。对炎症性肠病患者和不同半球优势的个体测量了以下参数：（1）血浆HMG CoA还原酶、地高辛、多萜醇、泛醌和镁水平；（2）色氨酸/酪氨酸分解代谢模式；（3）自由基代谢；（4）糖缀合物代谢；（5）膜组成和红细胞膜钠钾ATP酶活性。采用方差分析进行统计分析。炎症性肠病患者中，地高辛合成增加，多萜醇和糖缀合物水平升高，泛醌水平降低，自由基水平升高。色氨酸分解代谢产物增加，酪氨酸分解代谢产物减少。这些患者组中红细胞膜胆固醇与磷脂比率增加，糖缀合物水平降低。炎症性肠病与类异戊二烯途径上调及下丘脑地高辛分泌增加有关。这可能导致免疫激活、糖蛋白肠道抗原呈递缺陷、自身免疫以及在其发病机制中起重要作用的类精神分裂症性精神病。炎症性肠病中获得的生化模式与通过双耳分听测试在左利手/右半球优势个体中获得的模式相似。但所有消化性溃疡病患者通过双耳分听测试均为右利手/左半球优势。半球化学优势与利手或双耳分听测试无关。炎症性肠病发生在化学性右半球优势个体中，是脑功能改变的一种反映。
