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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Utilization of alpha-ketoisocaproate for synthesis of hepatic export proteins and peripheral proteins in normal and cirrhotic subjects.

The ratio R, defined as (percent of dose of 14C)/(percent of dose of 3H) in the leucine of plasma fibrinogen, albumin, immunoglobulin G (IgG), red cell globin, and salivary mucin, was measured in 7 normal adults and in 5 cirrhotic patients during continuous intragastric infusion of 1-14C-labeled alpha-ketoisocaproate (KIC) and 3H-labeled leucine. The ratio R measured in whole body protein has been shown in rat experiments to be a measure of the nutritional efficiency of KIC relative to leucine. In normal subjects, R in albumin and fibrinogen became constant (0.63 +/- 0.05) after the third hour and were indistinguishable from one another. The ratio R in IgG was similar and constant. The ratio R in plasma leucine (0.62 +/- 0.06) was significantly lower than R in mucin (0.86 +/- 0.04) or globin (0.73 +/- 0.04), indicating that these latter proteins derive a significant fraction of their leucine from KIC transaminated locally, rather than from circulating leucine. Results in 5 cirrhotic patients were the same, except that R in IgG and R in globin were significantly increased. Thus, cirrhosis does not alter the efficiency, relative to leucine, with which oral KIC is used for synthesis of export proteins by the liver, but increases the efficiency with which it is used for the synthesis of some proteins peripherally.[1]


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