Katz M L, Gerhardt K O
Department of Ophthalmology, University of Missouri School of Medicine, Columbia 65212.
Mech Ageing Dev. 1990 Apr 30;53(3):277-90. doi: 10.1016/0047-6374(90)90045-h.
Hereditary ceroid-lipofuscinoses are neurodegenerative disorders characterized by the accumulation in numerous tissues of a storage material with lipofuscin-like fluorescence properties. Investigations were undertaken to determine the chemical nature of this storage material isolated from the cerebral cortex of human subjects with the late infantile form of the disease. The storage material was mainly protein that consisted of a mixture of polypeptides ranging in apparent molecular weight from 13 to 67 kDa. Protein-bound fluorophores apparently were largely responsible for the autofluorescence of the storage bodies. The disease-related storage body protein was rich in S-methylmethionine [(3-amino-3-carboxypropyl) dimethyl sulfonium ion], an amino acid that does not normally occur in animal proteins. Methylation of proteins to form this unusual charged amino acid may impair proteolytic degradation or other aspects of protein metabolism, and account for the accumulation of protein-filled inclusions in cells of individuals with ceroid-lipofuscinoses. Similar amino acid modifications that block proteolysis could be involved in age pigment accumulation.
遗传性类脂褐质沉积症是一种神经退行性疾病，其特征是在许多组织中积累具有类脂褐质样荧光特性的储存物质。开展了相关研究，以确定从患有晚期婴儿型该疾病的人类受试者大脑皮质中分离出的这种储存物质的化学性质。该储存物质主要是蛋白质，由表观分子量在13至67 kDa之间的多种多肽混合物组成。与蛋白质结合的荧光团显然是储存体自发荧光的主要原因。与疾病相关的储存体蛋白富含S-甲基蛋氨酸[（3-氨基-3-羧丙基）二甲基锍离子]，这种氨基酸通常不存在于动物蛋白中。蛋白质甲基化形成这种异常带电氨基酸可能会损害蛋白水解降解或蛋白质代谢的其他方面，并解释了类脂褐质沉积症患者细胞中充满蛋白质的内含物的积累。类似的阻断蛋白水解的氨基酸修饰可能与老年色素积累有关。
