CYSTINE LEVELS, CYSTINE FLUX, AND PROTEIN CATABOLISM IN CANCER CACHEXIA, HIV SIV INFECTION, AND SENESCENCE/

Patients with skeletal muscle catabolism (cachexia) fail to conserve t he skeletal muscle protein and release lar re amounts of nitrogen as u rea. Previous studies suggest that the threshold for the conversion of amino acids into other forms of chemical energy and the concomitant p roduction of urea are regulated by the plasma cystine level and hepati c cysteine catabolism. Studies of plasma amino acid exchange rates in the lower extremities now show that healthy young subjects regulate th eir plasma cystine level in a process that may be described as control led constructive catabolism. The term controlled describes the fact th at the release of cystine and other amino acids from the peripheral ti ssue is negatively correlated with (certain) plasma amino acid levels. The term constructive describes the fact that the release of cystine is correlated with an increase of the plasma cystine level. The regula tion of the plasma cystine level is disturbed in conditions with progr essive skeletal muscle catabolism including cancer, HIV infection, and old age. These conditions show also a low plasma glutamine:cystine ra tio indicative of an impaired hepatic cystine catabolism. In HIV (+) p atients and SIV-infected macaques, a decrease of the plasma cystine le vel was found to coincide with the decrease of CD4(+) T cells.