Substrate balances across colonic carcinomas in humans.
To investigate the utilization of nutrients by malignant tumors in humans, the balances of energy-yielding substrates and amino acids across colonic carcinomas were assessed in 17 patients during surgery. Blood samples were taken from an artery and the main tumor-draining vein, which was also used for determining tumor blood flow (direct venous outflow technique). Additionally, the substrate exchange by peripheral tissues was studied (femoral arteriovenous differences, venous occlusion plethysmography). Mean blood flow was greater in the carcinomas than in the leg tissues (43.2 versus 2.5 ml/100 ml/min; P < 0.001). There was a negative correlation between tumor blood flow and tumor weight (r = -0.87; P < 0.001). Glucose net uptake and lactate release by the malignancies exceeded the peripheral exchange rates 30- and 43-fold, respectively (mean values different at P < 0.001). The molar ratio of lactate output to glucose consumption was 0.78 in the tumors and 0.48 in the leg tissues (P < 0.05). Regarding free fatty acid and ketone body balances, no significant tumor-periphery differences were noted. The carcinomas utilized branched chain amino acids and serine, while alanine and, in particular, ammonia were released in large amounts. Net glutamine retention was not consistently observed. It is concluded that the energy metabolism of human colonic carcinomas relies predominantly on glucose, with fat-derived calories making no appreciable contribution. The impaired nutritive perfusion of malignant tumors appears to favor glycolysis and to limit both glucose oxidation and glutaminolysis. The present study has shown that the procedure chosen for the assessment of trans-tumor substrate flux rates is a workable and valid model for analyzing metabolic balances across human colonic cancers in vivo.
Holm
E
E
Department of Pathophysiology, Medical Clinic I Mannheim, Theodor Kutzer Ufer, Germany.
Hagmüller
E
E
Staedt
U
U
Schlickeiser
G
G
Günther
H J
HJ
Leweling
H
H
Tokus
M
M
Kollmar
H B
HB
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D003110:Colonic Neoplasms / Q000098:blood supply / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007657:Ketone Bodies / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D000596:Amino Acids; D007657:Ketone Bodies; D000641:Ammonia; D005947:Glucose