Glutamine and Alanine Kinetics in Humans: Role of the Liver.

The liver is considered the major site of glutamine and alanine (but not leucine) handling. To directly test this hypothesis in humans, we measured glutamine and alanine kinetics during the anhepatic phase of liver transplantation and immediately (15 min) after the liver replacement. Fifteen subjects who underwent liver transplantation for localized cancer in hepatic cyrrhosis (LTX) and 8 healthy controls (CON) were studied with a bolus of [1,2-[sup.13][C.sub.2]]glutamine (LTX=6, CON=4) or [3-[sup.13]C]alanine (LTX=9, CON=4) that was administered after the recipient's liver was removed. Blood was sampled to follow the decay of the bolus in the time-window (approx. 60min) prior to the anastomosis of the transplanted liver and, in 10 LTX, 15-min thereafter. Alanine and glutamine clearances were estimated using two-compartmental models. Results are as follows:


Before LTX After LTX

Concentration
([micro]mol/l)

Glutamine 759 [+ or -] 63(b) 615 [+ or -] 61(a)
Alanine 940 [+ or -] 82(b) 737 [+ or -] 96(ab)
Leucine 142 [+ or -] 12 152 [+ or -] 12

Clearance
(ml/kg/min)

Glutamine 5.8 [+ or -] 1.1(b)
Alanine 13.7 [+ or -] 1.4(b)

CON

Concentration
([micro]mol/l)

Glutamine 538 [+ or -] 18
Alanine 384 [+ or -] 87
Leucine 127 [+ or -] 12

Clearance
(ml/kg/min)

Glutamine 12.8 [+ or -] 1.8
Alanine 19.2 [+ or -] 2.3


(a) p<0.01 vs before liver,

(b) p<0.05 vs CON.

After liver replacement also glutamine and alanine enrichments were reduced by 26 [+ or -] 5%. In summary, in the absence of the liver the alanine and the glutamine concentration increased and their clearance was reduced, and they were restored toward normal by the liver replacement. In contrast, the leucine concentration was unchanged. These results demonstrate that in humans the liver is a major site of glutamine and alanine disposal, whereas leucine is preferentially disposed in the peripheral tissues.

ALBERTO BATTEZZATI, ANNALISA FATTORINI, ANDREA CAUMO, ENRICO REGALIA, RAFFAELE ROMITO, JORGELINA COPPA, DWIGHT E. MATTHEWS, VINCENZO MAZZAFERRO, LIVIO LUZI, Milano, Italy

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