Gross A, Hack V, Stahl-Hennig C, Dröge W
Department of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
AIDS Res Hum Retroviruses. 1996 Nov 20;12(17):1639-41. doi: 10.1089/aid.1996.12.1639.
To establish whether the low cysteine and glutathione levels in HIV-infected patients and SIV-infected rhesus macaques may be consequences of an abnormal cysteine catabolism, we analyzed sulfate and glutathione levels in macaques. Muscle tissue (m. vastus lateralis and m. gastrocnemius) of SIV-infected macaques (n = 25) had higher sulfate and lower glutathione and glutamate levels than that of uninfected controls (n =9). Hepatic tissue, in contrast, showed decreased sulfate and glutathione disulfide (GSSG) levels, and increased gamma-glutamylcysteine synthetase (gamma-GCS) activity. These findings suggest drainage of the cysteine pool by increased cysteine catabolism in skeletal muscle tissue, and by increased hepatic glutathione biosynthesis. Cachectic macaques also showed increased urea levels and decreased glutamine/urea ratios in the liver, which are obviously related to the abnormal urea excretion and negative nitrogen balance commonly observed in cachexia. As urea production and net glutamine synthesis in the liver are strongly influenced by proton-generating processes, the abnormal hepatic urea production may be the direct consequence of the cysteine deficiency and the decreased catabolic conversion of cysteine into sulfate and protons in the liver.
为了确定HIV感染患者和SIV感染恒河猴体内半胱氨酸和谷胱甘肽水平较低是否可能是半胱氨酸分解代谢异常的结果，我们分析了恒河猴体内的硫酸盐和谷胱甘肽水平。与未感染的对照组（n = 9）相比，SIV感染的恒河猴（n = 25）的肌肉组织（股外侧肌和腓肠肌）中硫酸盐水平较高，而谷胱甘肽和谷氨酸水平较低。相比之下，肝脏组织中的硫酸盐和谷胱甘肽二硫化物（GSSG）水平降低，γ-谷氨酰半胱氨酸合成酶（γ-GCS）活性增加。这些发现表明，骨骼肌组织中半胱氨酸分解代谢增加以及肝脏中谷胱甘肽生物合成增加导致了半胱氨酸池的流失。恶病质的恒河猴肝脏中的尿素水平也升高，谷氨酰胺/尿素比值降低，这显然与恶病质中常见的异常尿素排泄和负氮平衡有关。由于肝脏中的尿素生成和净谷氨酰胺合成受到质子生成过程的强烈影响，肝脏中异常的尿素生成可能是半胱氨酸缺乏以及肝脏中半胱氨酸分解代谢转化为硫酸盐和质子减少的直接后果。
