Relationships between plasma isotope enrichments of leucine and α-ketoisocaproic acid during continuous infusion of labelled leucine

The ratio at steady-state of alpha-ketoisocaproic acid (KIC) to leucine 13C enrichments in plasma during continuous infusion of 13C]leucine was examined in 58 studies under a variety of conditions. The ratio was lower (P less than 0.001) in 'arterialized' venous plasma (mean +/- SD 0.85 +/- 0.09) than in deep venous plasma (0.95 +/- 0.08), the sampling site enrichment differences being greater for leucine than for KIC. Variation in the ratio between the various conditions studied was largely explained by analytical variation. Three normal subjects were given an intravenous bolus dose of L-1-13C, 15N]leucine. Both 13C]KIC and 13C]leucine appeared quantitatively in plasma within 10 min, indicating that both transamination of leucine and KIC, and their equilibration between intracellular fluid and plasma, is rapid. This study suggests that changes in sampling site, rather than in study conditions, are more likely to lead to variation in the KIC:leucine enrichment ratio. The lesser variation for KIC, and the rapid equilibration of the 13C]leucine bolus, favour KIC as tracee for 13C]leucine protein turnover studies.