Mechanisms of accelerated hepatic glutamine efflux in the tumour-bearing rat.
The mechanisms potentially controlling the net release of glutamine by the liver that occurs in tumour-bearing rats were investigated. Studies were undertaken when the tumour comprised approximately 7% (15 +/- 2 g) of total body weight. Hepatic glutamine gradient ratios were calculated by dividing hepatic glutamine content by arterial blood glutamine concentration. Both sodium-dependent and sodium-independent hepatocyte carrier-mediated glutamine transport were evaluated employing hepatic plasma membrane vesicles (HPMVs). In TBR the hepatic glutamine gradient ratio doubled (P < 0.001) secondary to a 52% increase in hepatic content (P < 0.005) and a 16% decrease in circulating glutamine (P < 0.001). Sodium-dependent glutamine transport was increased in HPMVs from TBR secondary to a 24 +/- 4% increase in the maximal velocity of transport (Vmax; P < 0.01) without alteration in apparent transporter affinity (Km). Saturable sodium-independent carrier-mediated glutamine transport was increased in HPMVs from TBR over CONT to a much greater relative degree owing to a 2.7-fold increase in transport Vmax (P < 0.05) without a change in transport Km. The accelerated hepatic efflux of glutamine which characterizes malignant growth appears to be the result of both mass-action gradient phenomena and alterations at the level of hepatocyte membrane transport activity.
Pacitti
A J
AJ
Department of Surgery, University of Florida, Gainesville 32610.
Chen
M K
MK
Bland
K I
KI
Copeland
E M
EM
Souba
W W
WW
D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D005354:Fibrosarcoma / Q000378:metabolism*; D005973:Glutamine / Q000032:analysis / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000378:metabolism
D005973:Glutamine; D012964:Sodium