Increased Whole-Body Protein and Glutamine Turnover in Advanced Cancer Is Not Matched by an Increased Muscle Protein and Glutamine Turnover

Abstract

In the progress of cancer major disturbances in protein and glutamine metabolism have been observed. Muscle is the major protein pool and glutamine source in the body. The aim of this study was to investigate whether changes in whole-body protein and glutamine turnover, induced by cancer, are matched by similar changes in regional muscle metabolism. A MCA sarcoma was implanted subcutaneously in female Lewis rats. Rats were studied bearing small (5–15% of body weight) or large (15–30% of body weight) tumor loads and compared with sham-implanted free-fed and pair-fed controls. Body composition was determined by the distribution of an ip bolus of3H2O. With the rat under anesthesia a primed constant infusion ofl-[2,6-3H]phenylalanine andl-[3,4-3H]glutamine was given, and at steady state, whole-body, hindquarter-muscle, and tumor protein and glutamine turnover were calculated using compartment modeling. Anorexia was not observed in tumor-bearing rats. A small decrease in host carcass weight was observed in large-tumor-bearing rats by decreased fat mass. Whole-body protein turnover increased from 115 ± 14 (nmole × 100 g body weight−1× min−1) in free-fed control rats to 239 ± 29 in the large-tumor-bearing rats. Net tumor protein synthesis accounted for 28 ± 1 and 49 ± 1 nmole × 100 g body weight−1× min−1. Muscle protein breakdown increased in the small-tumor-bearing group and decreased to control values in the large-tumor-bearing rats. Whole-body glutamine turnover remained unchanged in the small-tumor-bearing animals (2481 ± 248 and 1996 ± 268 nmole × 100 g body weight−1× min−1in control and small-tumor-bearing rats, respectively) and increased by 25% in the large-tumor-bearing animals. In contrast, muscle glutamine turnover more than doubled in the small-tumor-bearing group but returned to control values in the large-tumor-bearing animals. The current study show that in the presence of a small tumor whole-body protein turnover increased and that this was in part related to protein turnover of the tumor. Muscle protein breakdown increased in these rats with a concomitant increase in glutamine production from the hindquarter. In animals bearing larger tumors whole-body glutamine turnover increased. This increase, however, was only for a small part caused by tumor metabolism. Muscle glutamine turnover even decreased. Therefore, the increase in whole-body glutamine turnover appears to be caused by increased turnover in visceral organs.