Morrison L D, Becker L, Kish S J
Human Neurochemical Pathology Laboratory, Clarke Institute of Psychiatry, Toronto, Canada.
Brain Res Dev Brain Res. 1993 Jun 8;73(2):237-41. doi: 10.1016/0165-3806(93)90143-x.
Recent experimental animal studies have implicated brain polyamines as having roles in both brain development and human brain neurodegenerative conditions. In order to provide baseline information, in normal human brain, on one of the key polyamine synthesising enzymes, S-adenosylmethionine decarboxylase (SAMDC), we examined the sensitivity of this enzyme to various cofactors/inhibitors, its regional distribution, and influence of aging in neurologically normal autopsied human brain. SAMDC in normal human brain is similar to that reported in other mammalian cells with regard to substrate affinity (Km = 39 microM), marked sensitivity to putrescine activation (+600%), inhibition (methylglyoxalbisguanidine and MDL 73811), and pH optimum (7.2). There was an uneven distribution of enzyme activity in human brain, and of the 12 brain regions examined, the highest activity was observed in occipital, parietal, frontal and temporal cortices (36-58 pmol/h/mg protein); intermediate activity in cerebellar and insular cortex, pulvinar thalamus, caudate and putamen (12-27 pmol/h/mg protein); and lowest activity in medial-dorsal thalamus, lateral globus pallidus and white matter (< 11 pmol/h/mg protein). The influence of aging (1 day to 103 years) on SAMDC activity in occipital cortex, the region showing the highest activity in human brain (n = 59) was also determined. Enzyme activity increased by approximately 600% from age 6 months to near maximal levels at age 10 years, then remained generally unchanged up to 103 years. Since SAMDC is a key regulatory enzyme in the synthesis of spermidine and spermine, the marked increase in SAMDC activity in the neonate and the sustained high enzyme levels throughout adulthood, imply a role for these polyamines in both development and mature brain function.
最近的实验动物研究表明，脑内多胺在脑发育和人类脑退行性疾病中均发挥作用。为了提供正常人类大脑中关键多胺合成酶之一——S-腺苷甲硫氨酸脱羧酶（SAMDC）的基线信息，我们检测了该酶对各种辅助因子/抑制剂的敏感性、其区域分布以及衰老对神经正常的尸检人类大脑的影响。正常人类大脑中的SAMDC在底物亲和力（Km = 39 microM）、对腐胺激活（增加600%）、抑制（甲基乙二醛双脒基腙和MDL 73811）以及最适pH（7.2）方面与其他哺乳动物细胞中报道的情况相似。人类大脑中酶活性分布不均，在所检测的12个脑区中，枕叶、顶叶、额叶和颞叶皮质的活性最高（36 - 58 pmol/h/mg蛋白）；小脑和岛叶皮质、丘脑枕、尾状核和壳核的活性中等（12 - 27 pmol/h/mg蛋白）；内侧背侧丘脑、外侧苍白球和白质的活性最低（< 11 pmol/h/mg蛋白）。我们还确定了衰老（1天至103岁）对枕叶皮质中SAMDC活性的影响，枕叶皮质是人类大脑中活性最高的区域（n = 59）。酶活性从6个月龄时增加约600%，在10岁时接近最高水平，然后直至103岁一般保持不变。由于SAMDC是亚精胺和精胺合成中的关键调节酶，新生儿中SAMDC活性的显著增加以及成年期酶水平的持续高位，意味着这些多胺在发育和成熟脑功能中均发挥作用。
