ELEVATED HEPATIC GAMMA-GLUTAMYLCYSTEINE SYNTHETASE-ACTIVITY AND ABNORMAL SULFATE LEVELS IN LIVER AND MUSCLE-TISSUE MAY EXPLAIN ABNORMAL CYSTEINE AND GLUTATHIONE LEVELS IN SIV-INFECTED RHESUS MACAQUES

To establish whether the low cysteine and glutathione levels in HIV-in fected patients and SIV-infected rhesus macaques may be consequences o f an abnormal cysteine catabolism, we analyzed sulfate and glutathione levels in macaques, Muscle tissue (m. vastus lateralis and m. gastroc nemius) 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 glutat hione disulfide (GSSG) levels, and increased gamma-glutamylcysteine sy nthetase (gamma-GCS) activity, These findings suggest drainage of the cysteine pool by increased cysteine catabolism in skeletal muscle tiss ue, and by increased hepatic glutathione biosynthesis, Cachectic macaq ues also showed increased urea levels and decreased glutamine/urea rat ios in the liver, which are obviously related to the abnormal urea exc retion 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 an d the decreased catabolic conversion of cysteine into sulfate and prot ons in the liver.